All in One Day Seminar, Clinical Evidence Based Practice of Chiropractic: Ethics & Law, Basic Science (Nutrition), & Advanced Chiropractic Adjustive Technique.

California Approval Numbers: CA-A-21-05-04132 Advanced Adjustive Technique CA-A-21-05-04131 Basic Science (Nutrition) CA-A-21-05-04133 Ethics & Law

Arizona Approval Number: AZCE15016 All In One Day, Clinical Evidence Based Practice of Chiropractic: Ethics, Nutrition and Advanced Chiropractic Adjustive Technique Speaker: Mark Cymerint D.C. Triad Chiropractic Seminars - Seminar ! I may mention specific products or services that I personally use for the sole purpose of educational purposes. However, I am not endorsing any manufacturers, distributors, or other sellers of chiropractic products or services. Everything I mention related to seminar content is solely for educational purposes. PODCAST INFORMATION

!Dr. MC Organiccs Health Podcast !Find us on: Apple Podcast, Spotify, Buzzsprout, Google Podcast !www.drmcorganiccshealthpodcast.com 3 CONTACT ME!

Email: Office:

[email protected] (949) 707-5785

Website: Instagram:

TriadSeminars.com @OrganiccsAbsolutelyPure

Facebook: Podcast:

TriadSeminars DrMCOrganiccsHealthPodcast TO COMPLETE ONLINE CEU’S:

ALL ONLINE OR DVD SEMINARS MUST FILL OUT CE COMPLETION FORM FOUND AT WWW.TRIADSEMINARS.COM IN ORDER TO RECEIVE CREDIT HOURS. NO EXCEPTIONS!

Step 1: After completion of videos, go to triadseminars.com Step 2: At the top of the web page, click on CE Completion Forms. Step 3: If you are a CA doctor, click on CA DC Completion form. (Fill out) *If you are NOT a CA doc pick the other option. Step 4: Click submit.

Congrats! You will receive a pdf copy of your certificate via email within 3 days. *** FYI- There is a duplication FEE! Make sure you keep a copy of your certificate!!!

EXECUTIVE ORDER INFORMATION

MOST RECENT UPDATE: CHIROPRACTORS ARE ESSENTIAL WORKERS

www.covid19.ca.gov/essential-workforce/

Essential workforce, if remote working is not practical:

1.Health care providers and caregivers (including physicians, dentists, psychologists, mid-level practitioners, nurses, assistants, and aids; infection control and quality assurance personnel; pharmacists; physical, respiratory, speech and occupational therapists and assistants; social workers and providers serving individuals with disabilities including developmental disabilities; optometrists; speech pathologists; chiropractors; diagnostic and therapeutic technicians; and radiology technologists). CHIROPRACTORS ARE ESSENTIAL WORKERS

www.covid19.ca.gov/essential-workforce/

2. Workers required for effective clinical, command, infrastructure, support service, administrative, security and intelligence operations across the direct patient care and full healthcare and public health spectrum, including accounting, administrative, admitting and discharge, engineering, accrediting, certification, licensing, credentialing, epidemiological, source plasma and blood donation, food service, environmental services, housekeeping, medical records, information technology and operational technology, nutritionists, sanitarians; emergency medical services workers; prehospital workers including but not limited to urgent care workers; inpatient and hospital workers; outpatient care workers; home care workers; workers at long- term care facilities, residential and community-based providers; workplace safety workers). ESSENTIAL WORKER WHAT I AM IMPLEMENTING IN MY OFFICE:

! Only allowing the current patient to come into my office.

! Waiting room no longer used. Parking lot is the “new waiting room”

! Asking patients to stay in vehicles until we are ready to see them.

! Patients will call the office when they have arrived, and we will call when we are ready for them to come in.

! Plexi-glass/shields that sits on our front office counter for my front office staff

Source: coloradochiropractic.org/news WHAT I AM TELLING PATIENTS IN MY OFFICE:

• The best defense that your body can produces is a high functioning immune system is to make sure there is no nerve interference to the nervous system. • Therefore when you have mis-alignments, subluxations, postural imbalances they all interfere with the function of the nervous system which may reduce or lower the function or response of the immune system. • Always good to have a high functioning nervous system. • Do NOT promise any results or cures, prevention or forcefields to protect against a virus. • The best protection is a high functioning immune system- ALWAYS- not just during a “pandemic”

MISLEADING, DECEPTIVE, FALSE, OR UNETHICAL ADVERTISING

A. Chiropractors are responsible for the content of their advertising. B. The following types of advertising constitute misleading, deceptive, false, or unethical advertising pursuant to sections 12-215-115(1)(h), (o) and (5): 1. The misleading use of a claim regarding board certification or of an unearned or non-health degree in any advertisement or any claim that is likely to cause confusion or misunderstanding as to the credentials, education, or licensure of a healthcare professional; 2. Advertising that has the effect of intimidating or exerting undue pressure; 3. Advertising that uses unsubstantiated testimonials; 4. Advertising that creates an unjustified expectation or guarantees a cure; 5. Advertising that offers gratuitous services or discounts in a manner that is deceiving to the public; 6. Advertising of free or discounted x-ray services; or 7. Advertising that is otherwise misleading, deceptive, or false. 8. It must be clear to the public that the advertisement is from a doctor of chiropractic.

C. At the time any type of advertisement is placed, the chiropractor must possess, scientifically valid research that would substantiate the truthfulness of any assertion, omission, or claim set forth in the advertisement. Scientifically valid research includes applied research, basic research, and field-initiated research in which the rationale, design, and interpretation are soundly developed in accordance with principles of scientific research.

Source: coloradochiropractic.org/news CDC INFORMATION FOR CLINICIANS

The CDC also discussed how to determine which patients to refer for testing. CDC recommends using professional judgment to assess the presence of the following factors in presenting patients: Epidemiological factors such as being in close contact with a diagnosed patient or having been in an area of known community transmission Symptoms including: Fever Acute respiratory illness – cough, shortness of breath, difficulty breathing Myalgia Fatigue Persons over 65 years of age Persons with underlying conditions and co-morbidities CDC INFORMATION FOR CLINICIANS

The CDC recommends the following strategies for employers to use now. The CCA has summarized the strategies here but strongly urges clinic owners to click on the link at the end of this article to review the details provided for businesses by the CDC: Actively encourage sick employees to stay home; Separate sick employees; Emphasize staying home when sick, respiratory etiquette and hand hygiene by all employees; Perform routine environmental cleaning: Advise employees before traveling to take certain steps as outlined in the employer link below Additional Measures in Response to Currently Occurring Sporadic Importations of the COVID-19: Employees who are well but who have a sick family member at home with COVID-19 should notify their supervisor and refer to CDC guidance for how to conduct a risk assessment of their potential exposure. If an employee is confirmed to have COVID-19, employers should inform fellow employees of their possible exposure to COVID-19 in the workplace but maintain confidentiality as required by the Americans with Disabilities Act (ADA). Employees exposed to a co-worker with confirmed COVID-19 should refer to CDC guidance for how to conduct a risk assessment of their potential exposure. https://www.cdc.gov/coronavirus/2019-ncov/healthcare-facilities/index.html OVERVIEW

1. Nervous System is FIRST.

2. Balance the posture

3. Remove Interference - function optimally

4. Nutritional Recommendations for immune system to help increase

T Cell production and response from the nervous system.

5. Getting enough rest, proper exercise daily, & de-stressing

Cannabidiol:

Breaking into the Health Space NEW RESEARCH SUGGESTS TERPENES AND CBD WORK 2X’S BETTER FOR COVID-19 INFLAMMATION THAN CORTICOSTEROID

SOURCE: FORBES.COM JUL 21, 2020

In the fight against Covid-19, cytokine storms are one of the most deadly factors that doctors are battling. This symptom in severe cases of the novel coronavirus can lead to excessive inflammation, swelling, pain, and loss of organ function. It can even cause the immune system to ramp up so much that it starts killing the body’s own cells - instead of just fighting the infection. In serious cases, this can lead to death, as we’ve seen in many cases of severe Covid-19. In the last few months, researchers have been looking at whether cannabis, or it’s many chemical compounds, might help to fight this deadly effect by bringing down inflammation. Recently, we’ve seen positive results from studies suggesting that CBD, a compound in cannabis, may help fight these cytokine storms. Now early results from an ongoing Israeli study are adding to the chorus of researchers suggesting that cannabis’ ingredients could be a game changing treatment in the fight against Covid-19. But this study says that terpenes, compounds that provide the aroma and flavor in cannabis and many other plants, may lead to even better results than CBD alone, and might outperform conventional treatments like corticosteroids. Reports from the study show that a combination of CBD with terpenes was 3 times more effective at inhibiting cytokine activity than dexamethasone, a corticosteroid which a recent study found to be an effective treatment for Covid-19 cytokine storms.

The new terpene study is being performed by two Israeli research and development companies, Eybna which specializes in terpene based medicines, and CannaSoul Analytics which is led by Prof. David “Dedi” Meiri, PhD a well known cannabis researcher and biochemist who has studied cannabis’ use for conditions like cancer and Alzheimer's disease. This new study was designed to find out whether anti-inflammatory terpenes might help bring down dangerous cytokine storms, and if they could, how they compared to other available treatments.

The study looks at a proprietary terpene formulation called NT-VRL™, which was created by Eybna to treat inflammatory conditions such as the cytokine storm syndrome found in Covid-19 patients. The formulation contains 30 individual terpenes that are potential anti-inflammatory agents, and considered generally safe for consumption. Data scientist Nadav Eyal, who is Co-Founder & CEO at Eybna, explains that they utilized “biological data mining, data processing and formulation design” to create a “formulation effectively targeting specific health conditions” such as cytokine storms. He says that this method of development “is opening a new world for synergistically- effective natural formulations - holding therapeutic capabilities in which single Active Pharmaceutical Ingredients will have difficulties to match.”

Each compound was tested to see how it impacted cytokine activity, and the results are somewhat shocking. Not only was the terpene formulation able to inhibit the cytokine activity, (with better results using higher doses), but it also outperformed both CBD and dexamethasone. CBD alone inhibited around 75% of the cytokines on average, while the terpenes alone inhibited around 80%, suggesting that Eybna’s terpene blend may be even more effective than CBD for inflammation reduction. Still, the best results came from the combination of CBD and the NT- VRL™ terpene formulation, which was able to inhibit around 90% of the tested cytokines. In comparison, dexamethasone was only able to inhibit around 30% of the cytokines, suggesting that the combination of CBD and terpenes may be 2 times more effective than the current recommended treatment. WHAT IS CBD?

● Cannabidiol: Non-psychoactive cannabinoid

○ Analgesic ○ Anti-inflammatory ○ Anti-convulsant ○ Anti-spasmodic ○ Neuroprotective

Lucas, C. J., Galettis, P., & Schneider, J. (2018). The Pharmacokinetics and the Pharmacodynamics of Cannabinoids. British Journal of Clinical Pharmacology. doi:10.1111/bcp.13710 WHAT IS CBN?

! Cannabinol: Non-psychoactive cannabinoid ! Sedative ! Anti-inflammatory ! Anti-convulsant ! Bone formation ! Effective against MRSA ! For burns ! Keratinocytes in psoriasis

Lucas, C. J., Galettis, P., & Schneider, J. (2018). The Pharmacokinetics and the Pharmacodynamics of Cannabinoids. British Journal of Clinical Pharmacology. doi:10.1111/bcp.13710 WHAT ARE TERPENES?

!Fragrant essential oils found in plants, including hemp

!Myrcene (most abundant terpene in Cannabis) ! Analgesic ! Anti-inflammatory ! Anti-bacterial ! Enhances transdermal absorption

Russo, E. B. (2008). Cannabinoids in the management of difficult to treat pain. Therapeutics and Clinical Risk Management, 4(1), 245-259. WHAT IS THE ENDOCANNABINOID SYSTEM?

! Physiological system that works to maintain homeostasis ! It was named after the Cannabis plant that discovered it

Dustin Solak. Introduction to the Endocannabinoid System - NORML - Working to Reform Marijuana Laws. http://norml.org/library/ item/introduction-to-the-endocannabinoid-system. Accessed September 19, 2018. WHAT MAKES UP THE ENDOCANNABINOID SYSTEM?

! Endocannabinoids (endogenous ligands) ! Cannabinoid receptors (CB1 & CB2) ! Metabolizing enzymes WHAT ARE CANNABINOID RECEPTORS?

!The two primary receptors: !CB1 ! Mostly in the central nervous system !CB2 ! Mostly in the peripheral tissues ! mediator for suppressing pain & inflammation

Dustin Solak. Introduction to the Endocannabinoid System - NORML - Working to Reform Marijuana Laws. http://norml.org/library/ item/introduction-to-the-endocannabinoid-system. Accessed September 19, 2018. ACTIVATION OR INHIBITION OF CANNABINOID RECEPTORS

!Physiological Actions ! Inflammation ! Immune recognition and antitumor effects ! Locomotor activity ! Cognition & memory

Fine, P. G. F., & Rosenfeld, M. J. (2013). The Endocannabinoid System, Cannabinoids, and Pain. Rambam Maimonides Medical Journal, 4(4), 1-15.

HOW DOES CBD DIFFER FROM THC?

!THC: Most abundant psychoactive compound found in Cannabis. !CBD: Second most abundant non- psychoactive compound found in Cannabis.

Dustin Solak. Introduction to the Endocannabinoid System - NORML - Working to Reform Marijuana Laws. http://norml.org/ library/item/introduction-to-the-endocannabinoid-system. Accessed September 19, 2018. HOW DOES CBD DIFFER FROM THC?

! THC has high affinity for CB1 and CB2 receptors ! CB1 mediated psychoactivity- creates “high” feeling ! CBD has weak affinity for CB1 and CB2 receptors ! Lacks CB1 mediated psychoactivity- no “high” feeling

Dustin Solak. Introduction to the Endocannabinoid System - NORML - Working to Reform Marijuana Laws. http://norml.org/library/ item/introduction-to-the-endocannabinoid-system. Accessed September 19, 2018. WHAT SHOULD I LOOK FOR WHEN BUYING CBD?

!Consider extraction methods:

!Alcohol/Solvent Extraction !CO2 Extraction

!Be cautious of products with: !Flavors, sugars, unpronounceable ingredients ALCOHOL SOLVENT EXTRACTION ( WORST METHOD)

! Dangerous and cheap extraction method ! Ethanol, low-grade alcohol & butane most commonly used ! Chlorophyll extracted together with cannabinoids & terpenes results in undesirable end product – leaves dark color and bitter flavor ! Additional post processing required to remove the chlorophyll reducing potency of the oil ! Destroys plant waxes ! Toxic solvent residues remain in the end-product SUPERCRITICAL CO2 EXTRACTION

! Most superior CBD extraction method ! Most expensive ! The pressure and temperature of carbon dioxide (CO2) is manipulated over time to reach supercritical phase ! CO2 passed through high-quality hemp ! CO2 extracts oils without denaturing the phytocannabinoids, terpenes & flavonoids ! No residue results in pure end product SERVING SIZE RECOMMENDATIONS

!What works for me, will not necessarily work for you

!Start low, go slow and increase as needed

!Start with recommended serving size ! Assess how you feel after one week CBD SAFETY PROFILE

!Does not alter HR, BP, or body temperature !No negative influence on food intake, gastrointestinal transit, psychomotor or psychological functions

Iffland, K., & Grotenhermen, F. (2017). An update on safety and side effects of cannabidiol: A review of clinical data and relevant animal studies. Cannabis and Cannabinoid Research, 2(1), 139-154. doi:10.1089/can.2016.0034 WHO REPORT ON CBD SAFETY/USE 2017

“In humans, CBD exhibits no effects indicative of any abuse or dependence potential.”

CANNABIDIOL (CBD) Pre-Review Report Agenda Item 5.2 Geneva, 6-10 November 2017. Expert Committee on Drug Dependence Thirty-ninth Meeting. http://www.who.int/ medicines/access/controlled-substances/5.2_CBD.pdf. Accessed October 7, 2018. THE POTENTIAL OF CBD

!Homeostatic regulator !Pain & Inflammation !Anxiety !Sleep !GI Disorders !Crohn’s Disease !Irritable Bowel Syndrome

Pagano, E., Capasso, R., Piscitelli, F., Romano, B., Parisi, O. A., Finizio, S., et al. (2016). An orally active cannabis extract with high content in cannabidiol attenuates chemically- induced intestinal inflammation and hypermotility in the mouse. Frontiers in Pharmacology, 7(341), 1-10. doi:10.3389/fphar.2016.00341. Russo, E.B. (2016). Clinical endocannabinoid deficiency reconsidered: current research supports the theory in migraine, fibromyalgia, irritable bowel, and other treatment- resistant syndromes. Cannabis and Cannabinoid Research, 1(1), 154-165. METHODS OF USE

! Oral ~ 6% bioavailability (gel capsules or oil immediately swallowed) ! Undergoes extensive hepatic first-pass metabolism ! Slow working & requires higher serving sizes

! Inhalation ~ 31% bioavailability (vaporizing) ! Avoids extensive hepatic first-pass metabolism ! More instantaneous ! Requires lower serving sizes ! Consider people who have issues with asthma, SOB METHODS OF USE

! Oromucosal 30% bioavailability~ plasma concentrations higher than oral; lower than inhalation ! Avoids extensive hepatic first-pass metabolism ! Rapid absorption (useful for symptoms requiring rapid relief)

! Sublingual !Hold under the tongue 60-90 seconds

! Buccal !Hold between the gums and cheek 60-90 seconds METHODS OF USE

! Topical administration 30% bioavailability – HIGH ABSORPTION RATE ! Avoids first-pass metabolism ! Used for:

! Inflammation / pain

! Itch

! Acne ! Fungal infection

Lucas, C. J., Galettis, P., & Schneider, J. (2018). The Pharmacokinetics and the Pharmacodynamics of Cannabinoids. British Journal of Clinical Pharmacology. doi:10.1111/bcp.13710 WHAT CONCENTRATION OF CBD DO I NEED?

500mg, 750mg, 1000mg: • used by those trying to target a specific health concern

2500mg: • for those who have experience with CBD and require a larger serving size to meet needs REFERENCES: CANNABIDIOL (CBD) Pre-Review Report Agenda Item 5.2 Geneva, 6-10 November 2017. Expert Committee on Drug Dependence Thirty-ninth Meeting. http://www.who.int/medicines/access/ controlled-substances/5.2_CBD.pdf. Accessed October 7, 2018.

Carroon, J., & Phillips, J. A. (2018). A cross-sectional study of cannabidiol users. Cannabis and Cannabinoid Research, 3(1), 152-161. doi:10.1089/can.2018.0006

De Gregoria, D., McLaughlin R. J., Posa, L., Ochoa-Sanches, R., Enns, J., Lopez-Canul, M., et al. (2018). Cannabidiol modulates serotonergic transmission and prevents allodynia and anxiety-like behavior in a model of neuropathic pain. Pain. Published Ahead of Print. doi:10.1097/ j.pain.0000000000001386

Dustin Solak. Introduction to the Endocannabinoid System - NORML - Working to Reform Marijuana Laws. http://norml.org/library/item/introduction-to-the-endocannabinoid-system. Accessed September 19, 2018.

Fine, P. G. F., & Rosenfeld, M. J. (2013). The Endocannabinoid System, Cannabinoids, and Pain. Rambam Maimonides Medical Journal, 4(4), 1-15.

Hammel, D. C., Zhang, L. P., Ma, F., Abshire, S. M., Mcllwrath, S. L., Stinchcomb, A. L., et al. (2016). Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. European Journal of Pain, 16(11), 1248-1257. doi:10.1038/nm.2235 REFERENCES:

Iffland, K., & Grotenhermen, F. (2017). An update on safety and side effects of cannabidiol: A review of clinical data and relevant animal studies. Cannabis and Cannabinoid Research, 2(1), 139-154. doi:10.1089/can.2016.0034

Lucas, C. J., Galettis, P., & Schneider, J. (2018). The Pharmacokinetics and the Pharmacodynamics of Cannabinoids. British Journal of Clinical Pharmacology. doi:10.1111/bcp.13710

Philpott, H. T., O’Brien, M & McDougall, J. J. (2017). Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis. Pain, 158(12), 2442-2451

Russo, E. B. (2008). Cannabinoids in the management of difficult to treat pain. Therapeutics and Clinical Risk Management, 4(1), 245-259. REFERENCES:

Lucas, C. J., Galettis, P., & Schneider, J. (2018). The Pharmacokinetics and the Pharmacodynamics of Cannabinoids. British Journal of Clinical Pharmacology. doi:10.1111/ bcp.13710

Linares, I. M. P., Guimaraes, F. S., Eckeli, A., Crippa, A. C. S., Zuardi, A. W., Souza, J. D. S., et al. (2018). No acute effects of cannabidiol on the sleep-wake cycle of healthy subjects: a randomized, double-blind, placebo-controlled, crossover study. Frontiers in Pharmacology, 9(315), 1-8. doi:10.3389/fphar.2018.00315

Mandolini, G. M., Lazzaretti, M., Pigoni, A., Oldani, L., Delvecchio, G., & Brambilla, P. (2018). Pharmacological properties of cannabidiol in the treatment of psychiatric disorders: a critical overview. Epidemiology and Psychiatric Sciences, 27, 327-335. doi:10.1017/S2045796018000239

Philpott, H. T., O’Brien, M & McDougall, J. J. (2017). Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis. Pain, 158(12), 2442-2451

Russo, E. B. (2008). Cannabinoids in the management of difficult to treat pain. Therapeutics and Clinical Risk Management, 4(1), 245-259. ACM UPDATE 2-7-19 ! VA Reminder for Chiropractic & Acupuncture ! There are Veterans everywhere in need of your care, and by simply joining the network ! We have the information on our website under client forms and strongly encourage you to join Tri-West now as a Choice Provider. For the low cost of $15 per month ! The application is a tricky one, and needs to be filled out in a special manner or you will be enrolled in all of the bad carriers as well, so when completing the application please send it to us to proof before submitting it. ACM UPDATE – COVID RELIEF OPTIONS

! There are two immediate options for assistance through the SBA available to all small businesses. ! PPP Paycheck Protection Program which is forgivable if used toward payroll and overhead ! EIDL Economic Injury Disaster Loan which is a 30 year very low interest loan, requiring repayment beginning in 1 year. This may end up being partially forgivable as things are evolving quickly with the SBA and the rules are changing frequently. ! All information is available at SBA.GOV . The process is not terribly difficult but will require past tax returns and business financials. CORRECT POSTURE FOR SLEEP MORE THAN 70 MILLION PEOPLE IN THE DECREAS US AND SLEEP & ED QUALITY QUALITY CANAD IMMUNE BRAIN OF SLEEP OF LIFE A ARE HEALTH FUNCTIO AFFECTE N. D BY A SLEEP PROBLE M. Facts About Sleep • Sleep is important for neural development, learning, memory, emotional regulation, cardiovascular and metabolic function, and cellular toxin removal. (1) • Sleep posture, mattress, and pillow all contribute to over all quality of sleep. • Not getting enough sleep can cause excessive drowsiness, which as been associated with an increase risk of work related injuries (1) • In just 24 hours without sleep, humans experience dramatically decreased metabolic activity in the brain, decreased release of growth hormone, and decreased immune system function.

! If you sleep on your side, draw your legs up slightly towards your chest and put a pillow between your legs. SLEEP ! If possible, try to not put weight on your arms, this can cause problems with circulation and place pressure on your nerves which may POSITIONS cause a pins and needles sensation. ! If you sleep on your pack: try placing a pillow under you knees to help maintain a neutral TO REDUCE lower back curvature. ! Sleeping on your stomach is discouraged - causes an unnecessary strain on your neck BACK PAIN which may lead to compression of nerves and muscle tightening or and pain. ! Motorized adjustable beds to different positions can solve many sleep problems. Also, type of mattress can affect overall quality of sleep. !Sleeping on a good mattress and pillow is important to support the body and keep it in a neutral position. MATTRESSES !The mattress can help support the spines natural curves & SLEEP !It has been found that a sagging mattress can negatively affect sleep quality (2)

! Custom Comfort Mattress (Only in Southern California ! If you call, ask for the Owner, Gary Trudell !Your ideally fitted pillow should support the head, neck, and shoulders, and should adapt to the different CHOOSING contours of these areas— this will optimize your THE RIGHT sleeping position throughout PILLOW the night (2) !Educating patients on sleep posture = improve sleep, reduce pain caused by poor posture, & increased energy REFERENCES

! 1) Mukherjee S, Patel SR, Kales SN, et al. An official American thoracic society statement: The importance of healthy sleep. Recommendations and future priorities. Am J Respir Crit Care Med. 2015; 191(12): 1450-8. doi: 10.1164/rccm.201504-0767ST. ! 2) Journal of the ACA [serial online]. Proper Sleep Ergonomics. 2011; 48(4): 1-2. Available from: CINAHL Plus with Full Text. Accessed August 24, 2016. ! 3) Sezgin M, Hasanefendioğlu EZ, Sungur MA, et al. Sleep quality in patients with chronic low back pain: A cross- sectional study assessing its relations with pain, functional status and quality of life. J Back Musculoskelet Rehabil. 2014; 28(3): 433-41. doi: 10.3233/BMR-140537. ! 4) www.mayoclinic.com ! 5) www.sleepfoundation.org ! 6) www.aasmnet.org NUTRITION

INFLAMMATION Definition, literature review Natural inflammation reduction treatment options, including nutritional supplements and special dietary recommendations for an anti- inflammatory protocol.

CAUSES OF INFLAMMATION[1]

!Pathogens (germs) like bacteria, viruses !External injuries like scrapes or foreign objects !Effects of chemicals or radiation !Any “-itis.”

What is an inflammation?. Institute for Quality and Efficiency in Health Care (IQWiG). 2015. Available at: https://www.ncbi.nlm.nih.gov/ pubmedhealth/PMH0072482/. Accessed October 12, 2016. INFLAMMATION & AUTOIMMUNE DISEASE [1]

! Autoimmune Disease = immune system attacks itself causing harmful inflammatory responses:

! Rheumatoid arthritis - joints inflamed ! Psoriasis ! Inflammation of the bowel- Crohn’s disease or ulcerative colitis

What is an inflammation?. Institute for Quality and Efficiency in Health Care (IQWiG). 2015. Available at: https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072482/. Accessed October 12, 2016. SOURCES

! Maple C, McLaren M, Bancroft A, Ho M, Belch JJF. Dietary supplementation with omega 3 and omega 6 fatty acids reduces induced white blood cell aggregation in healthy volunteers. Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA). 1998;58:365-368. ! Calder PC. Omega‐3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology? British Journal of Clinical Pharmacology. 2013;75:645-662. ! Tilg H. Cruciferous vegetables: prototypic anti-inflammatory food components. Clinical Phytoscience. 2015;1:1-6. ! Kocabas H, Kocabas V, Buyukbas S, Salli A, Ugurlu H. Relationship of Cellular Oxidant and Antioxidant Status with Disease Activity in Patients with Rheumatoid Arthritis. Turkish Journal of Rheumatology. 2010;25:141-146. ! Al-Okbi SY. Nutraceuticals of anti-inflammatory activity as complementary therapy for rheumatoid arthritis. Toxicology and Industrial Health. 2014;30:738-749. ! Disease-modifying potential of Cinnamon extract in inflammation and arthritis. Australian Journal of Herbal Medicine. 2014;26:36. NUTRITION

• AMINO ACIDS • Definitions • Amino acids for cardiovascular health • Nitric oxide production WHAT IS AN AMINO ACID

!Organic compounds that contain an amine and carboxyl which are functional group, along with a side chain (R-group). !Building blocks of protein !Basis of all life, essential to all metabolic processes TITLE: FUNCTIONAL NITRIC OXIDE NUTRITION TO COMBAT CARDIOVASCULAR DISEASE

Purpose of review: To reveal the mechanisms of nitric oxide (NO) production in humans and how lifestyle, drug therapy, and hygienic practices can decrease NO production. Furthermore, to show how functional nitric oxide nutrition can overcome these limitations to restore endogenous NO production and combat cardiovascular disease.

Recent findings: Research over the past decade has revealed that inorganic nitrate and nitrite found naturally in green leafy vegetables and other vegetables such as beets can provide the human body with a source of bioactive nitric oxide. NO is one of the most important molecules produced within the cardiovascular system that maintains normal blood pressure and prevents inflammation, immune dysfunction, and oxidative stress, hallmarks of cardiovascular disease. This pathway is dependent upon the amount of inorganic nitrate and nitrite in the foods we eat, the presence of oral nitrate-reducing bacteria, and sufficient stomach acid production. The concept of food being medicine and medicine being food has lost its place in the practice and implementation of modern medicine over the past century. Certain dietary patterns and specific foods are known to confer very significant protective effects for many human diseases, including cardiovascular disease, the number one killer of men and women in the developed world. However, identification of single or multiple bioactive molecules that are responsible for these effects has escaped scientists and nutritionists for many years. This review will highlight the biochemical, physiological, and epidemiological basis for functional nitric oxide nutrition that can be safely and effectively utilized in patients.

Bryan NS. Functional Nitric Oxide Nutrition to Combat Cardiovascular Disease. Curr Atheroscler Rep. 2018;20(5):21. Published 2018 Mar 17. doi:10.1007/ s11883-018-0723-0 ARTICLE TITLE: DIETARY BRANCHED-CHAIN AMINO ACIDS REGULATE FOOD INTAKE PARTLY THROUGH INTESTINAL AND HYPOTHALAMIC AMINO ACID RECEPTORS IN PIGLETS. DATE & JOURNAL: J AGRIC FOOD CHEM. 2019 MAY 28

! Strategies to increase feed intake is of great importance for producing more meat in swine production. Intestinal and hypothalamic amino acid receptors are found largely participated in feed intake regulation. The purpose of the current research was to study the function of branched-chain amino acids (BCAAs) supplementation in the regulation of feed intake through sensors which can detect amino acids in piglets. Twenty-four piglets were assigned to four treatments and fed to one of the experimental diets for either short period (Expt. 1) or long period (Expt. 2): normal protein diet (NP, 20.04% CP), reduced-protein diet (RP, 17.05% CP), reduced-protein test diets supplemented with two doses of BCAAs (BCAA1, supplemented with 0.13% L-isoleucine, 0.09% L-leucine and 0.23% L-valine; BCAA2, supplemented with the 150% standardized ileal digestibility BCAAs requirement as recommended by the National Research Council (2012)). In Expt. 1, no differences were observed in feed intake among piglets fed with different diets (P > 0.05). In Expt. 2, when compared with the RP group, feed intake of piglets was significantly increased after sufficient BCAAs was supplemented in the BCAA1 group, which was associated with decreased cholecystokinin (CCK) secretion (P < 0.05), down-regulated expression of type 1 taste receptor 1/3 (T1R1/T1R3) in intestine, as well as increased expression of pro-opiomelanocortin (POMC) and activated general control nonderepressible 2 (GCN2) and eukaryotic initiation factor 2α (eIF2α) in the hypothalamus (P < 0.05). However, feed intake was decreased when the piglets were fed with BCAAs over supplemented diet for unknown reasons. In conclusion, our study confirmed that BCAAs deficit diet inhibited feed intake through two potential ways: regulating amino acid T1R1/T1R3 receptor in the intestine and/or activating GCN2/ eIF2α pathways in the hypothalamus. Curr Atheroscler Rep. 2018 Mar 17;20(5):21. doi: 10.1007/ s11883-018-0723-0.

FUNCTIONAL NITRIC OXIDE NUTRITION TO COMBAT CARDIOVASCULAR DISEASE

!Research over the past decade has revealed that inorganic nitrate and nitrite found naturally in green leafy vegetables and other vegetables such as beets can provide the human body with a source of bioactive nitric oxide. NO is one of the most important molecules produced within the cardiovascular system that maintains normal blood pressure and prevents inflammation, immune dysfunction, and oxidative stress, hallmarks of cardiovascular disease. This pathway is dependent upon the amount of inorganic nitrate and nitrite in the foods we eat, the presence of oral nitrate-reducing bacteria, and sufficient stomach acid production. The concept of food being medicine and medicine being food has lost its place in the practice and implementation of modern medicine over the past century. Certain dietary patterns and specific foods are known to confer very significant protective effects for many human diseases, including cardiovascular disease, the number one killer of men and women in the developed world. However, identification of single or multiple bioactive molecules that are responsible for these effects has escaped scientists and nutritionists for many years. This review will highlight the biochemical, physiological, and epidemiological basis for functional nitric oxide nutrition that can be safely and effectively utilized in patients. COMBINED SUPPLEMENTATION OF PRE-EXERCISE CARBOHYDRATE, ALANINE, AND PROLINE AND CONTINUOUS INTAKE OF GREEN TEA CATECHINS EFFECTIVELY BOOST ENDURANCE PREFORMANCE IN MICE

!Continuous intake of green tea catechins (GTC) increases fatty acid utilization as an energy source and improves endurance capacity. Conversely, the single pre- exercise intake of maltodextrin (MD) as a carbohydrate source and the gluconeogenic amino acids alanine (Ala) and proline (Pro) effectively maintain blood glucose levels and increase endurance performance. In this study, we investigated the synergistic combinational effect of these interventions on endurance performance in mice. Male BALB/c mice were fed a 0.5% GTC diet or Control diet for 8 weeks. Maximum running time was measured every 2 weeks. MD (2 g/kg body weight (B.W.)), MD (1 g/kg B.W.) + AlaPro (9:1, 1 g/kg B.W.), and vehicle were orally administrated 60 mins before measurements in each diet group. The GTC + MD + AlaPro group showed significantly higher endurance performance than the Control-Vehicle group at all measurements. Indirect calorimetry analysis during running exercise at 4 weeks in the Control and GTC groups supplemented with pre-exercise MD + AlaPro administration revealed significantly higher fat oxidation in the GTC groups compared to the Control group. The combined increase in fatty acid utilization through continuous GTC intake and pre-exercise MD + AlaPro carbohydrate energy supplementation synergistically improves endurance capacity.

Nutrients. 2018 Jul 19;10(7). pii: E925. doi: 10.3390/nu10070925. NITRIC OXIDE SYNTHASE INHIBITION AND OXIDATIVE STRESS IN CARDIOVASCULAR DISEASES: POSSIBLE THERAPEUTIC TARGETS?

Nitric oxide (NO) is synthetized enzymatically from l-arginine (l-Arg) by three NO synthase isoforms, iNOS, eNOS and nNOS. The synthesis of NO is selectively inhibited by guanidino-substituted analogs of l-Arg or methylarginines such as asymmetric dimethylarginine (ADMA), which results from protein degradation in cells. Many disease states, including cardiovascular diseases and diabetes, are associated with increased plasma levels of ADMA. The N-terminal catalytic domain of these NOS isoforms binds the heme prosthetic group as well as the redox cofactor, tetrahydrobiopterin (BH(4)) associated with a regulatory protein, calmodulin (CaM). The enzymatic activity of NOS depends on substrate and cofactor availability. The importance of BH(4) as a critical regulator of eNOS function suggests that BH(4) may be a rational therapeutic target in vascular disease states. BH(4) oxidation appears to be a major contributor to vascular dysfunction associated with hypertension, ischemia/reperfusion injury, diabetes and other cardiovascular diseases as it leads to the increased formation of oxygen-derived radicals due to NOS uncoupling rather than NO. Accordingly, abnormalities in vascular NO production and transport result in endothelial dysfunction leading to various cardiovascular disorders. However, some disorders including a wide range of functions in the neuronal, immune and cardiovascular system were associated with the over- production of NO. Inhibition of the enzyme should be a useful approach to treat these pathologies. Therefore, it appears that both a lack and excess of NO production in diseases can have various important pathological implications. In this context, NOS modulators (exogenous and endogenous) and their therapeutic effects are discussed.

Pharmacol Ther. 2013 Dec;140(3):239-57. doi: 10.1016/ j.pharmthera.2013.07.004. Epub 2013 Jul 13. HIGH ASYMMETRIC DIMETHYLARGININE, SYMMETRIC DIMETHYLARGININE AND L-ARGININE LEVELS IN MIGRAINE PATIENTS.

Experimental and clinical data strongly suggests that nitric oxide (NO) plays a pivotal role in migraine. This is also supported by studies of migraine induced by substances that release NO. NO is synthesized from L-arginine by endothelial NO synthase (NOS). Asymmetric dimethylarginine (ADMA) is the major endogenous competitive inhibitor of NOS. Symmetric dimethylarginine (SDMA) is an inactive stereoisomer of ADMA. It may reduce NO production by competing with arginine for cellular uptake. The aim of this study was to measure the levels of ADMA, SDMA and L-arginine in migraine patients during the interictal period. One hundred migraine patients and 100 healthy volunteers were recruited. The patients were in the interictal period and classified into two groups as having migraine with aura and migraine without aura. Their serum ADMA, SDMA and L-arginine levels were measured by high-performance liquid chromatography (HPLC) method. ADMA, SDMA and L-arginine levels were significantly higher in migraine patients compared to the control group. But there was no difference between the patients with and without aura. These results suggest that NOS inhibitors and L-arginine/NO pathway plays an important role in migraine pathophysiology.

Neurol Sci. 2017 Jul;38(7):1287-1291. doi: 10.1007/s10072-017-2970-1. Epub 2017 Apr 28.

BEFORE AFTER CURCUMIN, CURCUMINOIDS, & TURMERIC RESEARCH ARTICLE TITLE: CURCUMIN RELEASING EGGSHELL DERIVED CARBONATED APATITE NANOCARRIERS FOR COMBINED ANTI- CANCER, ANTI-INFLAMMATORY AND BONE REGENERATIVE THERAPY.

DATE & JOURNAL: J NANOSCI NANOTECHNOL. 2019 NOV

! Bone cancer or osteosarcoma is an aggressive cancer affecting the long bones and is treated by a combination of surgery and chemotherapy. Local drug delivery directly to the site of bone cancer and the use of plant-based drugs has been explored towards improving the efficacy and decreasing the toxicity of the anti-cancer drugs. Curcumin, derived from turmeric is highly effective against cancer cells and shows very low toxicity against normal cells. Bone repair is facilitated by use of bone substitutes such as bioceramics, amongst which the carbonated apatite (CA) nanocarriers closely mimic the natural bone mineral. In the current work, we have developed CA nanocarriers based local delivery of curcumin as an adjunct treatment for bone cancer. CA nanocarriers with 6 wt.% carbonate were prepared by wet chemical synthesis using synthetic derived (6SWCA) and eggshell derived (6EWCA) precursors along with hydroxyapatite (WHA) as a control. The X-ray diffraction (XRD) patterns showed the CAs to be phase pure with a mean crystallite size of 17 nm. The Fouriertransform infrared spectroscopy (FTIR) analysis of both CAs indicated the carbonate substitution as B-Type. The amount of carbonate substitution was observed to be around 6 wt.% using FTIR and CHNO elemental analyzer. The 6EWCA showed a greater loading (36%) and release (66%) of curcumin than 6SWCA and WHA nanocarriers. The bovine serum albumin (BSA) protein denaturation assay showed the curcumin loaded CAs to be highly anti-inflammatory while their anti- cancer activity was confirmed by the high cytotoxic activity against MG-63 human osteosarcoma cells. Conclusively, an eggshell derived apatite drug delivery system was found to be very suitable to cure osteosarcoma, prevent post-cancer inflammation and modulate bone repair and regeneration. ARTICLE TITLE: CURCUMIN: NEW INSIGHTS INTO AN ANCIENT INGREDIENT AGAINST CANCER.

DATE & JOURNAL: INT J MOL SCI. 2019 APR 12

! Cancer patients frequently use complementary medicine. Curcumin (CUR) and its derivates (from the extract of Curcuma longa L.) represent some of the most frequently used ones, having a long history in traditional Asian medicine. CUR was demonstrated, both in vitro and in vivo, to have significant anti- inflammatory effects, thus potentially counteracting cancer-promoting inflammation, which is a hallmark of cancer. CUR modulate a plethora of signaling pathways in cancer cells, comprising the NF-κB (nuclear factor k-light- chain-enhancer of activated B cells), the JAK/STAT (Janus-Kinase/Signal Transducers and Activators of Transcription), and the TGF-β (transforming growth factor-β) pathways. Furthermore, CUR confers properties of electron receptors, which destabilize radical oxygen species (ROS), explaining its antioxidant and anti-apopototic effects. Although CUR has a low bioavailability, its role in advanced cancer treatment and supportive care was addressed in numerous clinical trials. After promising results in phase I⁻II trials, multiple phase III trials in different indications are currently under way to test for direct anti-cancer effects. In addition, CUR exerts beneficial effects on cancer treatment-related neurotoxcity, cardiotoxicity, nephrotoxicity, hemato-toxicity, and others. More efficient galenic formulations are tested to optimze CUR's usability in cancer treatment. This review should provide a comprehensive overview of basic science, and pre-clinical and clinical data on CUR in the field of oncology. ARTICLE TITLE: THE IMPACT OF CURCUMIN AND ITS MODIFIED FORMULATIONS ON ALZHEIMER'S DISEASE.

DATE & JOURNAL: J CELL PHYSIOL. 2019 MAR 7

! Alzheimer's disease (AD) is a major health problem worldwide, with no effective treatment approach. Curcumin is the main ingredient of turmeric traditionally used in Asian medicine. Several experimental studies have indicated the protective effect of curcumin and its novel formulations in AD. Curcumin has antioxidant, anti-inflammatory and neurotrophic activities, proposing a strong potential to prevent neurodegenerative diseases. However, there are no sufficient clinical trials to confirm curcumin use in AD patients. Low bioavailability following oral administration of curcumin limits its usage in human. The present study was designed to gather the effects of curcumin and its modified formulations in human and experimental models of AD. ARTICLE TITLE: CURCUMA LONGA L. AMELIORATES ASTHMA CONTROL IN CHILDREN AND ADOLESCENTS: A RANDOMIZED, DOUBLE-BLIND, CONTROLLED TRIAL.

DATE & JOURNAL: J ETHNOPHARMACOL. 2019 APR 13

! ETHNOPHARMACOLOGICAL RELEVANCE: Roots of Curcuma longa L. are used as medicine for millennia. They possess several pharmacological properties, including anti-inflammatory action, and can be suitable for asthma treatment.

! AIM OF THE STUDY: We aimed to test the hypothesis that, in children and adolescents with persistent asthma, the administration of powdered roots of C. longa for 6 months, in addition to standard treatment, compared to placebo, will result in better disease control.

! PATIENTS AND METHODS: We conducted a randomized, double-blind, placebo-controlled, phase II clinical trial. Patients were randomly assigned to receive 30 mg/kg/day of C. longa for 6 months, or placebo. Data were collected prospectively. All patients were categorized for asthma severity and control according to GINA-2016 and underwent pulmonary function tests.

! RESULTS:Overall, both groups experienced amelioration of their frequency of symptoms and interference with normal activity, but no differences were found between the two treatment groups. However, patients receiving C. longa experienced less frequent nighttime awakenings, less frequent use of short-acting β-adrenergic agonists, and better disease control after 3 and 6 months.

! CONCLUSION: The powdered roots of C. longa led to less frequent nighttime awakenings, less frequent use of short- acting β-adrenergic agonists, and better disease control after 3 and 6 months, when compared to placebo. SYSTEMIC ADMINISTRATION OF CURCUMIN AFFECT ANXIETY- RELATED BEHAVIORS IN A RAT MODEL OF POST TRAUMATIC STRESS DISORDER VIA ACTIVATION OF SEROTONERGIC SYSTEMS

!Posttraumatic stress disorder (PTSD) is a trauma-induced psychiatric disease characterized by impaired hyperarousal, fear extermination, depression, anxiety, and amnesic symptoms that may include the release of monoamines in the dread circuit. Curcumin (CUR), a major diarylheptanoid and polyphenolic component of Curcuma longa, reportedly possesses several pharmacological features, including antidiabetic, antiatherosclerotic, anticancer, and neuropsychiatric actions. But the anxiolytic-like effects of CUR and its mechanism of action in PTSD are unclear. The current research measured some anxiety-related behavioral responses to examine the effects of CUR on symptoms of anxiety in rats after single prolonged stress (SPS) exposure by reversing the serotonin (5-HT) dysfunction. Rats received CUR (20, 50, or 100 mg/kg, i.p., once daily) for 14 days after SPS exposure. Administration of CUR significantly increased the number of central zone crossings in the open field test and reduced grooming behavior in the elevated plus maze (EPM) test and increased the number of open-arm visits on the EPM test. CUR administration significantly reduced freezing response to contextual fear conditioning. CUR recovered neurochemical abnormalities and SPS-induced decreased 5-HT tissue levels in the hippocampus, amygdala, and striatum. These results suggested that CUR has anxiolytic-like effects on biochemical and behavioral symptoms associated with anxiety. Thus, CUR may be a useful agent to alleviate or treat psychiatric disorders similar to those observed in patients with PTSD.

Evid Based Complement Alternat Med. 2018 Jun 19;2018:9041309. doi: 10.1155/2018/9041309. eCollection 2018. IS CURCUMIN A POSSIBILITY TO TREAT INFLAMMATORY BOWEL DISEASE?

!The inflammatory bowel diseases (IBDs) are mainly represented by Crohn's disease and Ulcerative colitis that are characterized by chronic and relapsing inflammatory processes of the gastrointestinal system. Curcuma longa L. is a plant with several medicinal properties, including anti-inflammatory effects, and curcumin is the most important compound derived from its rhizomes. As curcumin has remarkable anti-inflammatory actions, the aim of this work is to review the potential use of this compound in IBD patients. We consulted MEDLINE (PubMed/PMC), and the literature search was performed with the following combinations of terms "Inflammatory Bowel Diseases" and "Curcumin," "Crohn's Disease" and "Curcumin," "Ulcerative colitis" and "Curcumin." The inclusion criteria were articles that showed original studies with human models and the exclusion criteria were not full-text articles, articles not in English, poster presentations, letters, editorials, and articles not available. Curcumin interacts with receptors, growth and transcription factors, cytokines, enzymes, and genes leading to inhibitory effects on cyclooxygenase-1, tumor necrosis factor-α, interferon-γ, inducible nitric oxide synthase, transcriptional nuclear factor kappa B, and many other molecules associated with inflammatory processes. These molecules are critical factors in the positive regulation of inflammatory cytokines in inflammatory diseases, suggesting that curcumin may be considered as a new therapeutic agent for patients with IBD. Curcumin is a natural anti-inflammatory agent that represents an attractive, safe and inexpensive alternative for the treatment of IBD. Nevertheless, it is necessary to know the efficient and safe dose and consider its poor absorption.

J Med Food. 2018 Jun 29. doi: 10.1089/jmf.2017.0146 ANTI-INFLAMMATORY PROPERTIES OF CURCUMIN, A MAJOR CONSTITUENT OF CURCUMA LONGA: A REVIEW OF PRECLINICAL AND CLINICAL RESEARCH.

! Curcuma longa (turmeric) has a long history of use in Ayurvedic medicine as a treatment for inflammatory conditions. Turmeric constituents include the three curcuminoids: curcumin (diferuloylmethane; the primary constituent and the one responsible for its vibrant yellow color), demethoxycurcumin, and bisdemethoxycurcumin, as well as volatile oils (tumerone, atlantone, and zingiberone), sugars, proteins, and resins. While numerous pharmacological activities, including antioxidant and antimicrobial properties, have been attributed to curcumin, this article focuses on curcumin's anti-inflammatory properties and its use for inflammatory conditions. Curcumin's effect on cancer (from an anti-inflammatory perspective) will also be discussed; however, an exhaustive review of its many anticancer mechanisms is outside the scope of this article. Research has shown curcumin to be a highly pleiotropic molecule capable of interacting with numerous molecular targets involved in inflammation. Based on early cell culture and animal research, clinical trials indicate curcumin may have potential as a therapeutic agent in diseases such as inflammatory bowel disease, pancreatitis, arthritis, and chronic anterior uveitis, as well as certain types of cancer. Because of curcumin's rapid plasma clearance and conjugation, its therapeutic usefulness has been somewhat limited, leading researchers to investigate the benefits of complexing curcumin with other substances to increase systemic bioavailability. Numerous in-progress clinical trials should provide an even deeper understanding of the mechanisms and therapeutic potential of curcumin.

Altern Med Rev. 2009 Jun;14(2):141-53. RESEARCH ON PIPERINE (BLACK PEPPER) PIPERINE, AN ALKALOID OF BLACK PEPPER SEEDS CAN EFFECTIVELY INHIBIT THE ANTIVIRAL ENZYMES OF DENGUE AND EBOLA VIRUSES, AN IN SILICO MOLECULAR DOCKING STUDY Virusdisease . 2020 Sep

Abstract

Ebola and Dengue are the critical diseases caused by RNA viruses, especially in the tropical parts of the globe, including Asia and Africa, and no prominent therapeutic options are available so far. Here, an effort was made to evaluate the efficacy of black pepper (Piper nigrum L.) alkaloid Piperine as a potential drug through computational docking simulation. Eight structurally essential proteins of Dengue and Ebola virus were selected as in silico docking targets for Piperine. Absorption, Distribution, Metabolism, and Excretion profile showed that Piperine was safe and possessed significant drug-like properties. Molecular dynamic simulation and binding free energy calculation showed that Piperine could inhibit Methyltransferase (PDB id 1L9K) of Dengue and VP35 Interferon Inhibitory Domain (PDB id 3FKE) of Ebola virus in comparison with the commercial antiviral Ribavirin. Furthermore, statistical analysis based on multivariate and clustering approaches revealed that Piperine had more affinity towards viral proteins than that of Ribavirin.

Nag A, Chowdhury RR. Piperine, an alkaloid of black pepper seeds can effectively inhibit the antiviral enzymes of Dengue and Ebola viruses, an in silico molecular docking study. Virusdisease. 2020 Sep;31(3):308-315. doi: 10.1007/s13337-020-00619-6. Epub 2020 Aug 5. PMID: 32904842; PMCID: PMC7458978. ARTICLE TITLE: A SYSTEMATIC REVIEW ON BLACK PEPPER (PIPER NIGRUM L.): FROM FOLK USES TO PHARMACOLOGICAL APPLICATIONS.

DATE & JOURNAL: CRIT REV FOOD SCI NUTR. 2019 FEB 11

! Considered as the "King of spices", black pepper (Piper nigrum L.) is a widely used spice which adds flavor of its own to dishes, and also enhances the taste of other ingredients. Piper nigrum has also been extensively explored for its biological properties and its bioactive phyto-compounds. There is, however, no updated compilation of these available data to provide a complete profile of the medicinal aspects of P. nigrum. This study endeavors to systematically review scientific data on the traditional uses, phytochemical composition, and pharmacological properties of P. nigrum. Information was obtained using a combination of keywords via recognized electronic databases (e.g., Science Direct and Google Scholar). Google search was also used. Books and online materials were also considered, and the literature search was restricted to the English language. The country with the highest number of traditional reports of P. nigrum for both human and veterinary medicine was India, mostly for menstrual and ear-nose-throat disorders in human and gastrointestinal disorders in livestock. The seeds and fruits were mostly used, and the preferred mode of preparation was in powdered form, pills or tablets, and paste. Piper nigrum and its bioactive compounds were also found to possess important pharmacological properties. Antimicrobial activity was recorded against a wide range of pathogens via inhibition of biofilm, bacterial efflux pumps, bacterial swarming, and swimming motilities. Studies also reported its antioxidant effects against a series of reactive oxygen and nitrogen species including the scavenging of superoxide anion, hydrogen peroxide, nitric oxide, DPPH, ABTS, and reducing effect against ferric and molybdenum (VI). Improvement of antioxidant enzymes in vivo has also been reported. Piper nigrum also exhibited anticancer effect against a number of cell lines from breast, colon, cervical, and prostate through different mechanisms including cytotoxicity, apoptosis, autophagy, and interference with signaling pathways. Its antidiabetic property has also been confirmed in vivo as well as hypolipidemic activity as evidenced by decrease in the level of cholesterol, triglycerides, and low-density lipoprotein and increase in high-density lipoprotein. Piper nigrum also has anti-inflammatory, analgesic, anticonvulsant, and neuroprotective effects. The major bioactive compound identified in P. nigrum is piperine although other compounds are also present including piperic acid, piperlonguminine, pellitorine, piperolein B, piperamide, piperettine, and (-)-kusunokinin, which also showed biological potency. Most pharmacological studies were conducted in vitro (n = 60) while only 21 in vivo and 1 clinical trial were performed. Hence, more in vivo experiments using a pharmacokinetic and pharmacokinetic approach would be beneficial. As a conclusive remark, P. nigrum should not only be regarded as "King of spices" but can also be considered as part of the kingdom of medicinal agents, comprising a panoply of bioactive compounds with potential nutraceutical and pharmaceutical applications. BLACK PEPPER AND ITS PUNGENT PRINCIPLE-PIPERINE: A REVIEW OF DIVERSE PHYSIOLOGICAL EFFECTS.

! Black pepper (Piper nigrum) is one of the most widely used among spices. It is valued for its distinct biting quality attributed to the alkaloid, piperine. Black pepper is used not only in human dietaries but also for a variety of other purposes such as medicinal, as a preservative, and in perfumery. Many physiological effects of black pepper, its extracts, or its major active principle, piperine, have been reported in recent decades. Dietary piperine, by favorably stimulating the digestive enzymes of pancreas, enhances the digestive capacity and significantly reduces the gastrointestinal food transit time. Piperine has been demonstrated in in vitro studies to protect against oxidative damage by inhibiting or quenching free radicals and reactive oxygen species. Black pepper or piperine treatment has also been evidenced to lower lipid peroxidation in vivo and beneficially influence cellular thiol status, antioxidant molecules and antioxidant enzymes in a number of experimental situations of oxidative stress. The most far-reaching attribute of piperine has been its inhibitory influence on enzymatic drug biotransforming reactions in the liver. It strongly inhibits hepatic and intestinal aryl hydrocarbon hydroxylase and UDP-glucuronyl transferase. Piperine has been documented to enhance the bioavailability of a number of therapeutic drugs as well as phytochemicals by this very property. Piperine's bioavailability enhancing property is also partly attributed to increased absorption as a result of its effect on the ultrastructure of intestinal brush border. Although initially there were a few controversial reports regarding its safety as a food additive, such evidence has been questionable, and later studies have established the safety of black pepper or its active principle, piperine, in several animal studies. Piperine, while it is non-genotoxic, has in fact been found to possess anti-mutagenic and anti-tumor influences.

Crit Rev Food Sci Nutr. 2007;47(8):735-48. BIOLOGY-ORIENTED SYNTHESIS (BIOS) OF PIPERINE DERIVATIVES AND THEIR COMPARATIVE ANALGESIC AND ANTI-INFLAMMATORY ACTIVITIES.

!METHOD: Based on "biology-oriented synthesis approach", piperine alkaloid was isolated from Piper nigrum L. and some derivatives of piperine having azomethine, sulfamoyl, propanoyl, acetamoyl and heterocyclic oxadiazole were synthesized. The structures of synthetic derivatives were confirmed by using different spectroscopic techniques such as 1H-, 13C-NMR, EI-MS, and IR. Melting points were also determined for all compounds. Piperine and its all the synthetic derivatives were subjected to comparative in vivo evaluation of analgesic and antiinflammatory activities at the oral dose of 6 mg/ kg/day. Analgesic activity was evaluated by tail immersion, hot plate and acetic acid writhing methods. While, antiinflammatory activity was evaluated by carrageenan-induced paw inflammation. In silico studies of all synthetic compounds was also conducted on COX-2 and adenosine kinase enzymes.

!RESULTS: A number of derivatives showed enhanced antiinflammatory and analgesic activities as compared to piperine and standard drug diclofenac.

!CONCLUSION:The newly identified molecules may serve as lead for the future research in connection of potent and safer antiinflammatory and analgesic drug candidate.

Med Chem. 2018;14(3):269-280. doi: 10.2174/1573406413666170623083810. RESEARCH ON GINGER TITLE: GINGER EXTRACT ENHANCES ANTIOXIDANT ABILITY AND IMMUNITY OF LAYERS

! Abstract: This experiment was to investigate ginger extract on production performance, antioxidant ability and immunity of laying hens. A total of 600 Hy-Line brown laying hens aged at 25 wk old were randomly divided into 2 treatments, 4 replicates per treatment, 75 layers each replicate. The control group hens were fed a basal diet; the experimental group hens were fed basal diets with 0.1% ginger extract. The results were shown as follows: 1) ginger extract significantly enhanced laying rates (P < 0.05) and daily egg weight (P < 0.05), substantially reduced the ratio of feed to egg (P < 0.05) of the hens; 2) ginger extract did not change the activities of glutathione peroxidase (GSH-PX) and total antioxidant capacity (TAOC) but significantly improved plasma superoxide dismutase (SOD) activity (P < 0.05), reduced malondialdehyde (MDA) content (P < 0.05) of the birds; 3) ginger extract did not affect the contents of serum total protein (TP), albumin (ALB), globulin (GLB), but significantly increased lysozyme (LZM) activity (P < 0.05); 4) ginger extract also significantly reduced plasma prostaglandin E2 (PGE2) content (P < 0.05). This study shows that ginger extract not only can improve the birds' antioxidant capacity, enhance immune function, but also has a potential of reducing inflammatory response.

An S, Liu G, Guo X, An Y, Wang R. Ginger extract enhances antioxidant ability and immunity of layers. Anim Nutr. 2019;5(4):407-409. doi:10.1016/j.aninu.2019.05.003 PROTECTIVE AND THERAPEUTIC POTENTIAL OF GINGER (ZINGIBER OFFICINALE) EXTRACT AND [6]- GINGEROL IN CANCER: A COMPREHENSIVE REVIEW

Phytother Res . 2018 Oct.

Abstract

Natural dietary agents have attracted considerable attention due to their role in promoting health and reducing the risk of diseases including cancer. Ginger, one of the most ancient known spices, contains bioactive compounds with several health benefits. [6]-Gingerol constitutes the most pharmacologically active among such compounds. The aim of the present work was to review the literature pertaining to the use of ginger extract and [6]-gingerol against tumorigenic and oxidative and inflammatory processes associated with cancer, along with the underlying mechanisms of action involved in signaling pathways. This will shed some light on the protective or therapeutic role of ginger derivatives in oxidative and inflammatory regulations during metabolic disturbance and on the antiproliferative and anticancer properties. Data collected from experimental (in vitro or in vivo) and clinical studies discussed in this review indicate that ginger extract and [6]- gingerol exert their action through important mediators and pathways of cell signaling, including Bax/Bcl2, p38/MAPK, Nrf2, p65/NF-κB, TNF-α, ERK1/2, SAPK/JNK, ROS/NF-κB/COX-2, caspases-3, -9, and p53. This suggests that ginger derivatives, in the form of an extract or isolated compounds, exhibit relevant antiproliferative, antitumor, invasive, and anti-inflammatory activities.

de Lima RMT, Dos Reis AC, de Menezes APM, Santos JVO, Filho JWGO, Ferreira JRO, de Alencar MVOB, da Mata AMOF, Khan IN, Islam A, Uddin SJ, Ali ES, Islam MT, Tripathi S, Mishra SK, Mubarak MS, Melo-Cavalcante AAC. Protective and therapeutic potential of ginger (Zingiber officinale) extract and [6]-gingerol in cancer: A comprehensive review. Phytother Res. 2018 Oct;32(10):1885-1907. doi: 10.1002/ptr.6134. Epub 2018 Jul 16. PMID: 30009484. GINGER ( ZINGIBER OFFICINALE ROSCOE) IN THE PREVENTION OF AGEING AND DEGENERATIVE DISEASES: REVIEW OF CURRENT EVIDENCE

Evid Based Complement Alternat Med . 2019 Aug 20

Abstract

Currently, the age of the population is increasing as a result of increased life expectancy. Ageing is defined as the progressive loss of physiological integrity, which can be characterized by functional impairment and high vulnerability to various types of diseases, such as diabetes, hypertension, Alzheimer's disease (AD), Parkinson's disease (PD), and atherosclerosis. Numerous studies have reported that the presence of oxidative stress and inflammation contributes to the development of these diseases. In general, oxidative stress could induce proinflammatory cytokines and reduce cellular antioxidant capacity. Increased oxidative stress levels beyond the production of antioxidant agents cause oxidative damage to biological molecules, including DNA, protein, and carbohydrates, which affects normal cell signalling, cell growth, differentiation, and apoptosis and leads to disease pathogenesis. Since oxidative stress and inflammation contribute to these diseases, ginger (Zingiber officinale Roscoe) is one of the potential herbs that can be used to reduce the level of oxidative stress and inflammation. Ginger consists of two major active components, 6-gingerol and 6-shogaol, which are essential for preventing oxidative stress and inflammation. Thus, this paper will review the effects of ginger on ageing and degenerative diseases, including AD, PD, type 2 diabetes mellitus (DM), hypertension, and osteoarthritis.

Mohd Sahardi NFN, Makpol S. Ginger (Zingiber officinale Roscoe) in the Prevention of Ageing and Degenerative Diseases: Review of Current Evidence. Evid Based Complement Alternat Med. 2019 Aug 20;2019:5054395. doi: 10.1155/2019/5054395. PMID: 31531114; PMCID: PMC6721508. ARTICLE TITLE: CHEMOPREVENTIVE EFFICACY ZINGERONE (4-[4-HYDROXY-3- METHYLPHENYL] BUTAN-2-ONE) IN EXPERIMENTAL COLON CARCINOGENESIS IN WISTAR RATS.

DATE & JOURNAL: ENVIRON TOXICOL. 2019 MAY

! Colorectal cancer is one of the most common cancers worldwide. Development of naturally occurring inexpensive and safe alternatives can be effective in suppressing colon related proliferations. Zingerone (4-[4- hydroxy-3-methylphenyl] butan-2-one), a polyphenolic alkanone of ginger, has massive pharmacological properties and thus can be used as promising candidate against various ailments. In the current study, we aimed at demonstrating the protective effect of zingerone against experimental colon carcinogenesis and elucidating its possible mechanism by studying inflammatory and Nrf-2 signaling cascade. Four groups of animals (I-IV) were made with six animals each. Group I (control) was given normal saline orally. Group II was given 1,2-dimethylhydrazine (DMH) at the dose rate of 20 mg/kg body weight. Group III and IV were treated with DMH at the dose rate of 20 mg/kg body weight and also received oral treatment of zingerone at a dose rate of 50 and 100 mg/kg body weight, respectively, for first 5 weeks and animals were euthanized after 16 weeks. Our results reveal that DMH treated rats exhibited elevated ROS and MDA levels, increased activity of cytochrome P450 2E1 and serum marker enzyme carcinoembreyonic antigen (CEA), increased no of aberrant crypts of foci (ACF), and elevated expression of inflammatory and proliferative proteins. Nrf-2 was downregulated by DMH treatment. Treatment with zingerone to DMH treated rats, resulted in alterations in the activity of the cytochrome P450 2E1 and CEA. In addition, immunostaining of NF-kB-p65, COX-2, iNOS, and PCNA, Ki-67 was suppressed by zingerone. Furthermore, zingerone administration also attenuated the level of IL-6 and TNF-α and it also helps in preserving mucous layer. Thus, zingerone could be considered as a good chemopreventive agent in experimental model of colon carcinogenesis. Further studies are required to study other pathways involved in colon carcinogenesis and their modulation buy zingerone. BLACK GINGER EXTRACT INCREASES PHYSICAL FITNESS PERFORMANCE AND MUSCULAR ENDURANCE BY IMPROVING INFLAMMATION AND ENERGY METABOLISM.

! We previously reported that polymethoxyflavones (PMFs) in black ginger (Kaempferia parviflora) extract (KPE) increased energy production by activating AMP-activated protein kinase (AMPK) in C2C12 myoblasts. We herein evaluated the effects of KPE on physical fitness performance and muscular endurance in mice. Male mice were orally administered KPE for 4 weeks, and then forced swimming test, open-field test, inclined plane test, and wire hanging test were performed. KPE significantly increased the swimming time, motility after swimming, and grip strength. IL-6 and TNF-α mRNA expression levels were decreased in the soleus muscle, whereas peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and glycogen synthase mRNA expression levels, mitochondrial number, and glycogen content were increased. These results were in agreement with those obtained for KPE and PMFs in C2C12. Therefore, the activation of AMPK by PMFs may be one of the mechanisms by which KPE improves physical fitness performance and muscular endurance.

Heliyon. 2016 May 24;2(5):e00115. doi: 10.1016/j.heliyon.2016.e00115. eCollection 2016 May. ACUTE EFFECTS OF GINGER EXTRACT ON BIOCHEMICAL AND FUNCTIONAL SYMPTOMS OF DELAYED ONSET MUSCLE SORENESS.

! BACKGROUND: Inflammation and pain induced by delayed onset muscle soreness (DOMS) as a result of eccentric exercise (EE) or unaccustomed activity cause some difficulties in exercise for athletes. The purpose of this study was to survey the effect of ginger extract on biochemical and functional symptom of delayed onset muscle soreness.

! METHODS: In a quasi-experimental study, 36 healthy female subjects, who were recruited by intra dormitory calls, randomly divided into 3 groups, including: ginger intake 1 hour before exercise (GIBE), ginger intake immediately after exercise (GIAE) and placebo group (PL). Subjects consumed capsules contain 60 mg of ginger extract (equivalent of 2 g dried ginger powder) or placebo before and after exercise. The exercise protocol consisted of a 20 minute step test using a 46cm step at a rate of 15 steps per minute. The blood samples were taken before, 1, 24 and 48 hour after exercise to assay creatine kinase (CK) and interleukin-6 (IL-6). Muscle pain scores, isometric strength and circumference of thigh muscle, and hip range of motion were recorded at mentioned times. The analysis of variance (ANOVA) with repeated measure was used to determine the differences between groups.

! RESULTS: The results showed a significant reduction of pain in GIBE compared to GIAE after 24 and 48h of EE and GIAE compared to PL (p<0.05). IL-6 changed significantly in GIBE compared to PL (p<0.05) after 1, 24, and 48h after EE. The other factors didn't change meaningfully.

! CONCLUSION: The finding of this study suggests that 2 grams of ginger may have anti-inflammation and analgesic effect on DOMS

Med J Islam Repub Iran. 2015 Sep 12;29:261. eCollection 2015. THE EFFECTS OF PRE-EXERCISE GINGER SUPPLEMENTATION ON MUSCLE DAMAGE AND DELAYED ONSET MUSCLE SORENESS.

! Ginger possesses analgesic and pharmacological properties mimicking non-steroidal antiinflammatory drugs. We aimed to determine if ginger supplementation is efficacious for attenuating muscle damage and delayed onset muscle soreness (DOMS) following high-intensity resistance exercise. Following a 5-day supplementation period of placebo or 4 g ginger (randomized groups), 20 non-weight trained participants performed a high-intensity elbow flexor eccentric exercise protocol to induce muscle damage. Markers associated with muscle damage and DOMS were repeatedly measured before supplementation and for 4 days following the exercise protocol. Repeated measures analysis of variance revealed one repetition maximum lift decreased significantly 24 h post-exercise in both groups (p < 0.005), improved 48 h post-exercise only in the ginger group (p = 0.002), and improved at 72 (p = 0.021) and 96 h (p = 0.044) only in the placebo group. Blood creatine kinase significantly increased for both groups (p = 0.015) but continued to increase only in the ginger group 72 (p = 0.006) and 96 h (p = 0.027) post-exercise. Visual analog scale of pain was significantly elevated following eccentric exercise (p < 0.001) and was not influenced by ginger. In conclusion, 4 g of ginger supplementation may be used to accelerate recovery of muscle strength following intense exercise but does not influence indicators of muscle damage or DOMS.

Phytother Res. 2015 Jun;29(6):887-93. doi: 10.1002/ptr.5328. Epub 2015 Mar 18. SAFFRON, BROMELAIN, & EDTA RESEARCH BROMELAIN: A REVIEW ON ITS POTENTIAL AS A THERAPY FOR THE MANAGEMENT OF COVID-19

Niger J Physiol Sci . 2020 Jun 30

Abstract

Coronavirus Disease 2019 is a wide-spreading severe viral disease caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2) virus that needs to be urgently eradicated. SARS- COV-2 has infected millions of people worldwide and results in more than three hundred thousand deaths. Several repurposed drugs have failed to successfully eradicate the infection. Multiorgan failure caused by pronounced inflammation and systemic coagulation accounts for severe complications and death associated with diseases. Bromelain appears to be a potential candidate that may be used to inhibit or prevent the symptoms of the diseases. Its anti-inflammatory and anticoagulatory properties make it a potential agent that may slow the progression of the disease. In this review, we highlighted the beneficial effects of bromelain based on both experimental and clinical evidence that make bromelain a good candidate for the treatment of symptoms of CoVID-19 infection.

Owoyele BV, Bakare AO, Ologe MO. Bromelain: A Review on its Potential as a Therapy for the Management of Covid-19. Niger J Physiol Sci. 2020 Jun 30;35(1):10-19. PMID: 33084621. ARTICLE TITLE: BROMELAIN INHIBITS THE ABILITY OF COLORECTAL CANCER CELLS TO PROLIFERATE VIA ACTIVATION OF ROS PRODUCTION AND AUTOPHAGY.

DATE & JOURNAL: PLOS ONE. 2019 JAN 18

! Advanced colorectal cancer (CRC) survival rates are still low despite advances in cytotoxic and targeted therapies. The development of new effective or alternative therapies is therefore urgently needed. Bromelain, an extract of pineapple, was shown to have anticancer effects, but its mechanisms in CRC have not been fully explored. Therefore, the roles of bromelain in CRC progression were investigated using different CRC cell lines, a zebrafish model, and a xenograft mouse model. The anticancer mechanisms were explored by assessing the role of bromelain in inducing reactive oxygen species (ROS), superoxide, autophagosomes, and lysosomes. The role of bromelain in the induction of apoptosis was also assessed. It was found that bromelain inhibited CRC cell growth in cell lines and tumor growth in the zebrafish and xenograft mouse models. It also induced high levels of ROS and superoxide, plus autophagosome and lysosome formation. High levels of apoptosis were also induced, which were associated with elevated amounts of apoptotic proteins like apoptotic induction factor, Endo G, and caspases-3, -8, and -9 according to a qPCR analysis. In a Western blot analysis, increases in levels of ATG5/12, beclin, p62, and LC3 conversion rates were found after bromelain treatment. Levels of cleaved caspase-3, caspase-8, caspase-9, and poly(ADP ribose) polymerase (PARP)-1 increased after bromelain exposure. This study explored the role of bromelain in CRC while giving insights into its mechanisms of action. This compound can offer a cheap alternative to current therapies. NEPHROPROTECTIVE ROLE OF BROMELAIN AGAINST OXIDATIVE INJURY INDUCED BY ALUMINIUM IN RATS

Environ Toxicol Pharmacol . 2020 Nov

Abstract

The present study was designed to investigate the nephroprotective effect of bromelain against oxidative stress stimulated by aluminium chloride in rats. Rats were grouped as follows; group one was used as control while groups 2, 3 and 4 were treated orally with bromelain (250 mg/kg, daily), aluminium chloride (AlCl3; 34 mg/kg BW, every other day) and bromelain plus AlCl3 for 30 days, respectively. Administration of AlCl3 caused a significant reduction in rats' body and kidney weights, and increased Al accumulation in kidney tissue. Also, AlCl3 treatment elevated thiobarbituric acid reactive substances, hydrogen peroxide, kidney functions biomarkers levels and lactate dehydrogenase activity. While enzymatic (SOD, CAT, GPx, GR, GST) and non-enzymatic (GSH) antioxidants, protein content, and alkaline phosphatase activity were significantly decreased. In addition, significant alterations in lipid and protein profiles were detected. Furthermore, histopathological and immunohistochemical variations were seen in kidney sections supporting the obtained biochemical changes. Otherwise, rats supplemented with bromelain singly declined lipid peroxidation and improved most of the studied parameters. Moreover, rats pretreated with bromelain followed by AlCl3 intoxication showed significant alleviation in lipid peroxidation, antioxidant status and biochemical indices with respect to AlCl3 treated group. Conclusively, bromelain has beneficial protective effects and has the capability to counteract the toxic influence of AlCl3. So, bromelain might represent a novel approach in the therapy of metal toxicity because of its antioxidant and chelating properties.

El-Demerdash FM, Baghdadi HH, Ghanem NF, Mhanna ABA. Nephroprotective role of bromelain against oxidative injury induced by aluminium in rats. Environ Toxicol Pharmacol. 2020 Nov;80:103509. doi: 10.1016/j.etap.2020.103509. Epub 2020 Oct 1. PMID: 33010469. SAFFRON (ITS ACTIVE CONSTITUENT, CROCIN) SUPPLEMENTATION ATTENUATES LIPID PEROXIDATION AND PROTECTS AGAINST TISSUE INJURY.

! The aim of the current study was to investigate the outcomes in a rat model of an acute swimming exercise induced oxidative stress in brain, kidney, liver, skeletal and cardiac muscles using supplementation with crocin. Rats were divided into the eight groups; Normal Control (NC: Untreated and did not swim), Crocin Control (CC: Received crocin and did not swim), Exercise-1 (E-1: Untreated and swam), Exercise-24 (E-24: Untreated and swam), Exercise-48 (E-48: Untreated and swam), Exercise+Crocin-1 (EC-1: Received crocin and swam), Exercise+Crocin-24 (EC-24: Received crocin and swam), Exercise+Crocin-48 (EC-48: Received crocin and swam). The malondialdehyde (MDA) and xanthine oxidase (XO) enzymes levels increased after swimming in untreated and crocin treated groups, but there was a lower increase in crocin treated groups. The highest MDA levels in all tissues were observed in E-1 compared to all other groups. There were significant differences between control and exercise groups in MDA levels of tissues (p < 0.001). In contrast, there were significant differences between control and exercise groups in glutathione (GSH) levels of tissues.In addition, the crocin supplementation significantly increased GSH levels and decreased MDA and XO enzyme levels when compared to untreated exercise groups. Crocin can protect the tissues against exercise induced oxidative stress by enhancing antioxidant activity (Tab. 3, Fig. 1, Ref. 37).

Bratisl Lek Listy. 2016;117(7):381-7. PHARMACOKINETIC PROPERTIES OF SAFFRON AND ITS EurACTIVE J Drug Metab Pharmacokinet COMPONENTS . 2018 Aug

Abstract

Saffron as a medicinal plant has many therapeutic effects. Phytochemical studies have reported that saffron is composed of at least four active ingredients which include crocin, crocetin, picrocrocin and safranal. The carotenoids of saffron are sensitive to oxygen, light, heat and enzymatic oxidization. However, regulation of these factors is required for saffron quality. Some pharmacologic effects of saffron and its active compounds include cardioprotective, neuroprotective, memory enhancer, antidepressant and anxiolytic. Among more than 150 chemicals of saffron, the most biologically active components are two carotenoids including crocin and crocetin. Most of the pharmacokinetic studies are related to these compounds. The pharmacokinetic studies have shown that crocin is not available after oral administration in blood circulation. Crocin is converted to crocetin in intestine but after intravenous injection, the level of crocetin in plasma is low. Crocetin can distribute in different tissues because of weak interaction between crocetin and albumin. Also it can penetrate blood-brain barrier and reach CNS by passive transcellular diffusion; thus it can be effective in neurodegenerative disorders. The large portion of crocin is eliminated via feces.

Hosseini A, Razavi BM, Hosseinzadeh H. Pharmacokinetic Properties of Saffron and its Active Components. Eur J Drug Metab Pharmacokinet. 2018 Aug;43(4):383-390. doi: 10.1007/s13318-017-0449-3. PMID: 29134501. POTENTIAL ROLE OF BROMELAIN IN CLINICAL AND THERAPEUTIC APPLICATIONS.

! Pineapple has been used as part of traditional folk medicine since ancient times and it continues to be present in various herbal preparations. Bromelain is a complex mixture of protease extracted from the fruit or stem of the pineapple plant. Although the complete molecular mechanism of action of bromelain has not been completely identified, bromelain gained universal acceptability as a phytotherapeutic agent due to its history of safe use and lack of side effects. Bromelain is widely administered for its well-recognized properties, such as its anti-inflammatory, antithrombotic and fibrinolytic affects, anticancer activity and immunomodulatory effects, in addition to being a wound healing and circulatory improvement agent. The current review describes the promising clinical applications and therapeutic properties of bromelain.

Biomed Rep. 2016 Sep;5(3):283-288. Epub 2016 Jul 18. ANTICANCER PROPERTY OF BROMELAIN WITH THERAPEUTIC POTENTIAL IN MALIGNANT PERITONEAL MESOTHELIOMA

!Bromelain is a mixture of proteolytic enzymes that is capable of hydrolyzing glycosidic linkages in glycoprotein. Glycoprotein's are ubiquitously distributed throughout the body and serve a variety of physiologic functions. Faulty glycosylation of proteins may lead to cancer. Antitumor properties of bromelain have been demonstrated in both, in vitro and in vivo studies, along with scanty anecdotal human studies. Various mechanistic pathways have been proposed to explain the anticancer properties of bromelain. However, proteolysis by bromelain has been suggested as a main pathway by some researchers. MUC1 is a glycoprotein that provides tumor cells with invasive, metastatic, and chemo- resistant properties. To date, there is no study that examines the effect of bromelain on MUC1. However, the viability of MUC1 expressing pancreatic and breast cancer cells are adversely affected by bromelain. Further, the efficacy of cisplatin and 5-FU are enhanced by adjuvant treatment with bromelain, indicating that the barrier function of MUC1 may be affected. Other studies have also indicated that there is a greater accumulation of 5-FU in the cell compartment on treatment with 5-FU and bromelain. Malignant peritoneal mesothelioma (MPM) expresses MUC1 and initial studies have shown that the viability of MPM cells is adversely affected by exposure to bromelain. Further, bromelain in combination with either 5-FU or cisplatin, the efficacy of the chemotherapeutic drug is enhanced. Hence, current evidence indicates that bromelain may have the potential of being developed into an effective anticancer agent for MPM.

Biotechnol Prog. 2016 Jan-Feb;32(1):5-13. doi: 10.1002/btpr.2190. Epub 2015 Nov 17. REFERENCES

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NUTRITION

• Digestion Green Alkaline foods for fiber and digestion • Minerals and Collagen Protein • Colon Health TITLE: A RANDOMIZED CLINICAL TRIAL OF THE EFFECTS OF LEAFY GREEN VEGETABLES AND INORGANIC NITRATE ON BLOOD PRESSURE

Background: A diet rich in fruits and vegetables is associated with lowering of blood pressure (BP), but the nutrient(s) responsible for these effects remain unclear. Research suggests that inorganic nitrate present in leafy green vegetables is converted into NO in vivo to improve cardiovascular function.

Results: A total of 231 subjects (95%) completed the study. The insignificant change in ambulatory SBP (mean ± standard deviation) was -0.6 ± 6.2 mm Hg in the placebo group, -1.2 ± 6.8 mm Hg in the potassium nitrate group, and -0.5 ± 6.6 mm Hg in the leafy green vegetable group. There was no significant difference in change between the 3 groups.

Conclusions: A 5-wk dietary supplementation with leafy green vegetables or pills containing the same amount of inorganic nitrate does not decrease ambulatory SBP in subjects with elevated BP. This trial was registered at clinicaltrials.gov as NCT02916615.

Sundqvist ML, Larsen FJ, Carlström M, et al. A randomized clinical trial of the effects of leafy green vegetables and inorganic nitrate on blood pressure. Am J Clin Nutr. 2020;111(4):749-756. doi:10.1093/ajcn/nqaa024 TITLE: BIOACTIVITY EVALUATIONS OF LEAF EXTRACT FRACTIONS FROM YOUNG BARLEY GRASS AND CORRELATION WITH THEIR PHYTOCHEMICAL PROFILES

Abstract: Background: The pressed juice of Barley Grass (BG) has become very popular among people for various assumed benefits along with many testimonies of people who have been healed from various ailments such as anemia, cancer, GI problems by consuming BG. The aim of our research was to validate the claims of its medicinal values such as chemo- protective action, high anti-oxidants, RBC membrane stabilization activity, and toxicity level.

Conclusion: The study reveals the strong antioxidant and RBC membrane stabilization activity of BG. The Brine Shrimp Lethality Assay found extracts to be bioactive suggesting extracts as a promising candidate for plant-derived anti-tumor compounds. Further, studies are needed to validate the data on cancer cell lines.

Panthi M, Subba RK, Raut B, Khanal DP, Koirala N. Bioactivity evaluations of leaf extract fractions from young barley grass and correlation with their phytochemical profiles. BMC Complement Med Ther. 2020;20(1):64. Published 2020 Feb 28. doi:10.1186/s12906-020-2862-4 TITLE: EXTRACTION OF POLYSACCHARIDES FROM MACA: CHARACTERIZATION AND IMMUNOREGULATORY EFFECTS ON CD4 + T CELLS

Abstract -The immunomodulatory effects of maca polysaccharides (MCPs) on macrophages have been demonstrated in many studies. However, the effects of MCPs on CD4+ T cells have not been studied. Four water-soluble MCPs, labeled MCP1 (weight-average molecular weights [Mws] of 896.1 and 276.6 kDa), MCP2 (Mws of 337.8 and 219.0 kDa), MCP3 (Mws of 110.6, 58.1, and 38.9 kDa), and MCP4 (Mws of 15.7, 12.6, and 12.1 kDa), were obtained from maca by graded ethanol precipitation. The immunoregulatory effects of MCPs on CD4+ T cells were evaluated for the first time. The experimental results indicated that all MCPs had immunoregulatory effects on CD4+ T cells. However, the effects of MCP2 were stronger compared to the other three components, not only in promoting the proliferation of CD4+ T cells but also in terms of secretion of interferon-γ (IFN-γ). The molecular weight and monosaccharide compositions of MCPs were analyzed to explore the structure-activity relationship. The results suggested that the molecular weight and the galactosamine (GalN) of MCPs might be determining factors for its bioactivity. These findings suggest that the MCP2 isolated in our study have immune potentiation effects on CD4+ T cells.

Chang Y, Lu W, Chu Y, et al. Extraction of polysaccharides from maca: Characterization and immunoregulatory effects on CD4+ T cells. Int J Biol Macromol. 2020;154:477-485. doi:10.1016/j.ijbiomac.2020.03.098 TITLE: NOPAL (OPUNTIA SPP.) AND ITS EFFECTS ON METABOLIC SYNDROME: NEW INSIGHTS FOR THE USE OF A MILLENARY PLANT

Abstract- Background: Nopal (Opuntia spp.) is by excellence the most utilized cactus in human and animal nutrition. It is also a very noble plant; its main physicochemical, nutritional and nutraceutical characteristics allow the use of nopal in diverse food applications. Special focus has been given over the past decades in the use of Opuntia for the treatment of metabolic syndrome (MetS), which is predominantly related to Diabetes Mellitus. In this sense, the prevalence of MetS is increasing at a worldwide level. This in turn has led to a notorious demand for natural and nutraceutical food sources.

Conclusion: Nopal constitutes one of the most studied members of the Cactaceae family; its potential effects on human health have been described since ancient times, mostly through traditional medicine. The present work highlights the importance of this plant in the treatment of MetS related maladies and points out the importance of elucidating new compounds and their validation for the interactions of nutraceutical compounds which could be related to MetS.

Angulo-Bejarano PI, Gómez-García MDR, Valverde ME, Paredes-López O. Nopal (Opuntia spp.) and its Effects on Metabolic Syndrome: New Insights for the Use of a Millenary Plant. Curr Pharm Des. 2019;25(32):3457-3477. doi:10.2174/1381612825666191010171819 TITLE: ANTIOXIDANT, IMMUNOMODULATING, AND MICROBIAL-MODULATING ACTIVITIES OF THE SUSTAINABLE AND ECOFRIENDLY SPIRULINA

Abstract

The highly nutritional and ecofriendly Spirulina (Arthrospira platensis) has hypolipidemic, hypoglycemic, and antihypertensive properties. Spirulina contains functional compounds, such as phenolics, phycocyanins, and polysaccharides, with antioxidant, anti-inflammatory, and immunostimulating effects. Studies conducted on Spirulina suggest that it is safe in healthy subjects, but attitude to eating probably affects the acceptability of Spirulina containing foods. Although the antioxidant effect of Spirulina is confirmed by the intervention studies, the concerted modulation of antioxidant and inflammatory responses, suggested by in vitro and animal studies, requires more confirmation in humans. Spirulina supplements seem to affect more effectively the innate immunity, promoting the activity of natural killer cells. The effects on cytokines and on lymphocytes' proliferation depend on age, gender, and body weight differences. In this context, ageing and obesity are both associated with chronic low grade inflammation, immune impairment, and intestinal dysbiosis. Microbial-modulating activities have been reported in vitro, suggesting that the association of Spirulina and probiotics could represent a new strategy to improve the growth of beneficial intestinal microbiota. Although Spirulina might represent a functional food with potential beneficial effects on human health, the human interventions used only supplements. Therefore, the effect of food containing Spirulina should be evaluated in the future.

Finamore A, Palmery M, Bensehaila S, Peluso I. Antioxidant, Immunomodulating, and Microbial-Modulating Activities of the Sustainable and Ecofriendly Spirulina. Oxid Med Cell Longev. 2017;2017:3247528. doi:10.1155/2017/3247528 TITLE: FUNCTIONAL PROPERTIES OF SPINACH (SPINACIA OLERACEA L.) PHYTOCHEMICALS AND BIOACTIVES

Abstract Overwhelming evidence indicates that diets rich in fruits and vegetables are protective against common chronic diseases, such as cancer, obesity and cardiovascular disease. Leafy green vegetables, in particular, are recognized as having substantial health- promoting activities that are attributed to the functional properties of their nutrients and non- essential chemical compounds. Spinach (Spinacia oleracea L.) is widely regarded as a functional food due to its diverse nutritional composition, which includes vitamins and minerals, and to its phytochemicals and bioactives that promote health beyond basic nutrition. Spinach-derived phytochemicals and bioactives are able to (i) scavenge reactive oxygen species and prevent macromolecular oxidative damage, (ii) modulate expression and activity of genes involved in metabolism, proliferation, inflammation, and antioxidant defence, and (iii) curb food intake by inducing secretion of satiety hormones. These biological activities contribute to the anti-cancer, anti-obesity, hypoglycemic, and hypolipidemic properties of spinach. Despite these valuable attributes, spinach consumption remains low in comparison to other leafy green vegetables. This review examines the functional properties of spinach in cell culture, animals and humans with a focus on the molecular mechanisms by which spinach-derived non-essential phytochemicals and bioactives, such as glycolipids and thylakoids, impart their health benefits.

Roberts JL, Moreau R. Functional properties of spinach (Spinacia oleracea L.) phytochemicals and bioactives. Food Funct. 2016;7(8):3337-3353. doi:10.1039/c6fo00051g TITLE: TARGETING THE GUT MICROBIOTA BY DIETARY NUTRIENTS: A NEW AVENUE FOR HUMAN HEALTH

Abstract- The gut microbiota is a complex ecosystem consisted of trillions of microbes that have co-evolved with their host for hundreds of millions of years. During the last decade, a growing body of knowledge has suggested that there is a compelling set of connections among diet, gut microbiota and human health. Various physiological functions of the host, ranging from metabolic and immune regulation to nerve and endocrine development, are possibly mediated by the structural components of microbial cell or the products of microbial metabolism, which are greatly influenced by dietary macronutrients and micronutrients. Thus, governing the production and activity of these microbial-associated small molecules and metabolites through dietary intervention may provide promising strategies for the improvement of human health and disease. In this review article, we first provide an overview of current findings about the intimate interrelationships between diet and gut microbiota. We also introduce the physiological effects of some microbial-associated small molecules and metabolites on the host as well as the detailed signaling mechanisms.

Li D, Wang P, Wang P, Hu X, Chen F. Targeting the gut microbiota by dietary nutrients: A new avenue for human health. Crit Rev Food Sci Nutr. 2019;59(2):181- 195. doi:10.1080/10408398.2017.1363708 TITLE: THE FOOD-GUT HUMAN AXIS: THE EFFECTS OF DIET ON GUT MICROBIOTA AND METABOLOME

Abstract

Gut microbiota, the largest symbiont community hosted in human organism, is emerging as a pivotal player in the relationship between dietary habits and health. Oral and, especially, intestinal microbes metabolize dietary components, affecting human health by producing harmful or beneficial metabolites, which are involved in the incidence and progression of several intestinal related and non-related diseases. Habitual diet (Western, Agrarian and Mediterranean omnivore diets, vegetarian, vegan and gluten-free diets) drives the composition of the gut microbiota and metabolome. Within the dietary components, polymers (mainly fibers, proteins, fat and polyphenols) that are not hydrolyzed by human enzymes seem to be the main leads of the metabolic pathways of gut microbiota, which in turn directly influence the human metabolome. Specific relationships between diet and microbes, microbes and metabolites, microbes and immune functions and microbes and/or their metabolites and some human diseases are being established. Dietary treatments with fibers are the most effective to benefit the metabolome profile, by improving the synthesis of short chain fatty acids and decreasing the level of molecules, such as p-cresyl sulfate, indoxyl sulfate and trimethylamine N-oxide, involved in disease state. Based on the axis diet-microbiota-health, this review aims at describing the most recent knowledge oriented towards a profitable use of diet to provide benefits to human health, both directly and indirectly, through the activity of gut microbiota.

De Angelis M, Garruti G, Minervini F, Bonfrate L, Portincasa P, Gobbetti M. The Food-gut Human Axis: The Effects of Diet on Gut Microbiota and Metabolome. Curr Med Chem. 2019;26(19):3567-3583. doi:10.2174/0929867324666170428103848 TITLE: IMPACT OF A PROBIOTIC PRODUCT ON BOWEL HABITS AND MICROBIAL PROFILE IN PARTICIPANTS WITH FUNCTIONAL CONSTIPATION: A RANDOMIZED CONTROLLED TRIAL

Abstract - Objective: To investigate the clinical efficacy of a multi-strain probiotic product on bowel habits and microbial profile in participants with functional constipation.

Results: There were no significant between-group differences in the PAC-SYM score, despite significant within- group differences (P < 0.001) over the study period. The probiotic group showed a faster normalization of stool frequency and consistency, with most participants achieving a normalized profile after 1 week. Fecal samples of the probiotic group exhibited higher relative abundance of Ruminococcaceae (P = 0.0047), including the Ruminococcus genus, and lower relative abundance of Erysipelotrichaceae (P = 0.0172) at end-point compared with baseline. Placebo group samples showed similar abundance profiles over the study, with the exception of Clostridiaceae, which was lower at the study end-point (P = 0.0033). Among treated participants, all four probiotic strains were significantly more abundant after the intervention.

Conclusions: No significant differences were observed in symptomology, with both groups showing a more than 20% improvement. However, the probiotic helped modulate bowel function earlier than the placebo, with a corresponding shift to a more fibrolytic microbiota.

Martoni CJ, Evans M, Chow CT, Chan LS, Leyer G. Impact of a probiotic product on bowel habits and microbial profile in participants with functional constipation: A randomized controlled trial. J Dig Dis. 2019;20(9):435-446. doi:10.1111/1751-2980.12797 TITLE: THE CHEMICAL COMPOSITION AND NUTRITIONAL VALUE OF CHIA SEEDS-CURRENT STATE OF KNOWLEDGE

Abstract- Chia (Salvia hispanica) is an annual herbaceous plant, the seeds of which were consumed already thousands of years ago. Current research results indicate a high nutritive value for chia seeds and confirm their extensive health-promoting properties. Research indicates that components of chia seeds are ascribed a beneficial effect on the improvement of the blood lipid profile, through their hypotensive, hypoglycaemic, antimicrobial and immunostimulatory effects. This article provides a review of the most important information concerning the potential application of chia seeds in food production. The chemical composition of chia seeds is presented and the effect of their consumption on human health is discussed. Technological properties of chia seeds are shown and current legal regulations concerning their potential use in the food industry are presented.

Kulczyński B, Kobus-Cisowska J, Taczanowski M, Kmiecik D, Gramza-Michałowska A. The Chemical Composition and Nutritional Value of Chia Seeds-Current State of Knowledge. Nutrients. 2019;11(6):1242. Published 2019 May 31. doi:10.3390/nu11061242 TITLE: CHIA SEEDS (SALVIA HISPANICA): HEALTH PROMOTING PROPERTIES AND THERAPEUTIC APPLICATIONS – A REVIEW

Abstract Chia has been known for over 5,500 years. Chia seeds were one of the most important components of the diet of Mayas and Aztecs. The chemical composition and technological properties of chia give the plant a high nutritional potential. Chia is a good source of polyunsaturated fatty acids: omega-3 and omega-6, soluble dietary fiber. It also contains appreciable amount of proteins and phytochemicals. Nutritional value of chia is the reason why it is used in prophylaxis of several non-infectious diseases such as obesity, hypertension, cardiovascular diseases (CVDs), cancer and diabetes. Nutritional and therapeutic aspects of chia are currently being researched by many scientific centres. The aim of this article is to present the nutritional and therapeutic values of chia.

Marcinek K, Krejpcio Z. Chia seeds (Salvia hispanica): health promoting properties and therapeutic applications – a review. Rocz Panstw Zakl Hig. 2017;68(2):123- 129. TITLE: FLAXSEED BIOACTIVE COMPOUNDS AND COLORECTAL CANCER PREVENTION

Abstract

Purpose of review: Flaxseed and its bioactive components have been associated with a decreased risk of colorectal cancer incidence and progression. This review aims to summarize recent research regarding the role of flaxseed and each of its major dietary bioactive components in reducing colorectal cancer.

Recent findings: In both human and animal model experiments, flaxseed consumption had beneficial effects on colon physiology associated with reduction in colorectal cancer risk or occurrence. Considered separately, each of flaxseed's major bioactive components, including fiber, alpha-linolenic acid, lignans, and other phytochemicals, is also associated with decreased risk of colonic neoplasms and regulation of cell growth through several potential mechanisms. Collectively, experimental data suggests that consumption of flaxseed and/or its bioactive components may reduce colorectal cancer risk by a variety of mechanisms. Future studies should focus on the mechanisms by which whole flaxseed can prevent colorectal cancer..

DeLuca JAA, Garcia-Villatoro EL, Allred CD. Flaxseed Bioactive Compounds and Colorectal Cancer Prevention. Curr Oncol Rep. 2018;20(8):59. Published 2018 Jun 5. doi:10.1007/s11912-018-0704-z TITLE: CHIA SEEDS: AN ANCIENT GRAIN TRENDING IN MODERN HUMAN DIETS

Abstract

Currently, in order to ensure adequate intake of nutrients to complement the normal diet, the consumption of seeds such as Salvia hispanica L. (commonly known as chia seeds) is increasing. For this reason, investigations concerning the composition and potential health effects of chia seeds are being carried out. Moreover, the recent approval of chia seeds as a Novel Food by the European Parliament allows its consumption and incorporation in a wide range of foods; thus, they have become widely available. Concerning their nutritional aspects, chia seeds are an excellent source of fat (20% to 34%), particularly polyunsaturated fatty acids such as α-linolenic (60%) and linoleic (20%) acids. Moreover, high levels of protein (16% to 26%), mainly prolamins, and dietary fibre contents (23% to 41%) have been reported. Vitamins (mostly B complex) and minerals (calcium, phosphorus, and potassium, among others) have also been described in appreciable amounts. Additionally, due to the absence of gluten, these seeds are appropriate for coeliac patients. Regarding other bioactive compounds, chia seeds are also a source of antioxidants, such as chlorogenic and caffeic acids, quercetin and kaempferol. Due to their described composition, chia seeds have been related to different medicinal effects, particularly anti-inflammatory and antidiabetic activities and positive effects on cardiovascular disease and hypertension. The aim of this paper is to perform a systematic review of chia seeds to provide an update of the knowledge about their morphology, nutritional and chemical composition, possible human health benefits and role as a functional food.

Melo D , Machado TB , Oliveira MBPP . Chia seeds: an ancient grain trending in modern human diets. Food Funct. 2019;10(6):3068-3089. doi:10.1039/c9fo00239a TITLE: EFFECTS OF OAT BRAN ON NUTRIENT DIGESTIBILITY, INTESTINAL MICROBIOTA, AND INFLAMMATORY RESPONSES IN THE HINDGUT OF GROWING PIGS

Abstract- Oat bran has drawn great attention within human research for its potential role in improving gut health. However, research regarding the impact of oat bran on nutrient utilization and intestinal functions in pigs is limited. The purpose of this study was to investigate the effects of oat bran on nutrient digestibility, intestinal microbiota, and inflammatory responses in the hindgut of growing pigs. Twenty-six growing pigs were fed either a basal diet (CON) or a basal diet supplemented with 10% oat bran (OB) within a 28 day feeding trial. Results showed that digestibility of dietary gross energy, dry matter, organic matter, and crude protein were lower in the OB group compared to the CON group on day 14, but no differences were observed between the two groups on day 28. In the colon, the relative abundance of operational taxonomic units (OTUs) associated with Prevotella, Butyricicoccus, and Catenibacterium were higher, while those associated with Coprococcus and Desulfovibrio were lower in the OB group compared to the CON group. Oat bran decreased mRNA expression of caecal interleukin-8 (IL-8), as well as colonic IL-8, nuclear factor-κB (NF-κB), and tumor necrosis factor-α (TNF-α) of the pigs. In summary, oat bran treatment for 28 day did not affect dietary nutrient digestibility, but promoted the growth of cellulolytic bacteria and ameliorated inflammatory reactions in the hindgut of growing pigs.

He B, Bai Y, Jiang L, et al. Effects of Oat Bran on Nutrient Digestibility, Intestinal Microbiota, and Inflammatory Responses in the Hindgut of Growing Pigs. Int J Mol Sci. 2018;19(8):2407. Published 2018 Aug 15. doi:10.3390/ijms19082407 TITLE: OAT BRAN, BUT NOT ITS ISOLATED BIOACTIVE Β- GLUCANS OR POLYPHENOLS, HAVE A BIFIDOGENIC EFFECT IN AN IN VITRO FERMENTATION MODEL OF THE GUT MICROBIOTA

Abstract- Wholegrain oats are known to modulate the human gut microbiota and have prebiotic properties (increase the growth of some health-promoting bacterial genera within the colon). Research to date mainly attributes these effects to the fibre content; however, oat is also a rich dietary source of polyphenols, which may contribute to the positive modulation of gut microbiota. In vitro anaerobic batch-culture experiments were performed over 24 h to evaluate the impact of two different doses (1 and 3 % (w/v)) of oat bran, matched concentrations of β-glucan extract or polyphenol mix, on the human faecal microbiota composition using 16S RNA gene sequencing and SCFA analysis. Supplementation with oats increased the abundance of Proteobacteria (P <0·01) at 10 h, Bacteroidetes (P <0·05) at 24 h and concentrations of acetic and propionic acid increased at 10 and 24 h compared with the NC. Fermentation of the 1 % (w/v) oat bran resulted in significant increase in SCFA production at 24 h (86 (sd 27) v. 28 (sd 5) mm; P <0·05) and a bifidogenic effect, increasing the relative abundance of Bifidobacterium unassigned at 10 h and Bifidobacterium adolescentis (P <0·05) at 10 and 24 h compared with NC. Considering the β-glucan treatment induced an increase in the phylum Bacteroidetes at 24 h, it explains the Bacteriodetes effects of oats as a food matrix. The polyphenol mix induced an increase in Enterobacteriaceae family at 24 h. In conclusion, in this study, we found that oats increased bifidobacteria, acetic acid and propionic acid, and this is mediated by the synergy of all oat compounds within the complex food matrix, rather than its main bioactive β-glucan or polyphenols. Thus, oats as a whole food led to the greatest impact on the microbiota.

Kristek A, Wiese M, Heuer P, et al. Oat bran, but not its isolated bioactive β-glucans or polyphenols, have a bifidogenic effect in an in vitro fermentation model of the gut microbiota. Br J Nutr. 2019;121(5):549-559. doi:10.1017/S0007114518003501

ALKALINE GREENS TO DEAL WITH ACIDIFICATION

! Acid interferes with digestion food stagnates and rots lowering the pH of the body. ! A 16oz bottle of soda has a pH= 2. Very acidic. To bring the pH back up to our normal 7.3, we would have to dilute the soda with about 10 gallons of water. ! The blood must maintain a pH = 7.3-7.45. (Guyton) The body begins to sweep the extra acids into the tissues (muscles & joints). (lactic acid) ! Acidification will actually precipitate acids out of solution, in the form of crystals, salts, and stones (Kidney & Gall). SOURCES

1. http://greenopedia.com/alkaline-acid-food-chart/ MINERALS & COLLAGEN MINERALS !Functions of minerals:

!Structural: bones, teeth, ligaments

!Solutes and electrolytes in the blood

!Enzyme actions

!Nerve transmission !Muscle action BEST TYPE OF MINERAL SUPPLEMENTS

! CHELATED = a mineral is bound or stuck to certain carrier molecules or amino acid which result increased absorption ! Chelation can include minerals, vitamins, or enzymes. Minerals in food may be bound with organic molecules already in a chelated state. ! Albion Labs- TRAACS- The Real Amino Acid Chelate System

! Chelation Therapy = treatment for removing heavy metals from the blood. The toxic metals are bound to a therapeutic amino acid ligand called EDTA. ! CLICK HERE FOR VIDEO TITLE: SAFETY EVALUATION OF FERROUS BISGLYCINATE CHELATE

Abstract Ferrous bisglycinate chelate (Ferrochel) is a highly stable chelate that can be added to most foods. Data from human and animal studies indicate that the ferrous iron is readily bioavailable with fewer side-effects than the more commonly used iron salts. The acute oral LD50 for male and female Sprague-Dawley (S-D) rats is 2800 mg/kg body weight (560 mg/kg body weight iron [confdence limit (CL) 399-786] as the active ingredient). Male and female CD (Sprague Dawley-derived) rats were fed ferrous bisglycinate as a dietary admixture at doses of 0, 100, 250 and 500 mg/kg body weight/day. There were no biologically or statistically signifcant dose-related differences between the control and treated animals with respect to body weight gain, food consumption, food effciency, behavioural effects, clinical chemistries, haematology, absolute and relative organ weights, or gross and microscopic fndings. Hepatic non-heme iron concentrations were elevated, indicating that the ferrous iron had been absorbed. The no-observed-adverse-effect level (NOAEL) was 500 mg/kg body weight/ day, the highest dose tested.

Jeppsen RB, Borzelleca JF. Safety evaluation of ferrous bisglycinate chelate. Food Chem Toxicol. 1999 Jul;37(7):723-31. doi: 10.1016/s0278-6915(99)00052-6. PMID: 10496373. TITLE: EFFECTIVENESS OF TREATMENT OF IRON-DEFICIENCY ANEMIA IN INFANTS AND YOUNG CHILDREN WITH FERROUS BIS-GLYCINATE CHELATE

Abstract Forty infants, 6 to 36 mo old, with iron-defciency anemia (hemoglobin < 11 g/dL) were matched and assigned to two groups. One group received FeS0(4) and the other received ferrous bis-glycinate chelate at a dose of 5 mg of Fe daily per kilogram of body weight for 28 d. Both groups had signifcant hemoglobin increases (P < 0.001), but only the group treated with ferrous bis-glycinate chelate had signifcant increases (P < 0.005) in plasma ferritin. Apparent iron bioavailabilities were calculated at 26.7% for FeS0(4) and 90.9% for ferrous bis-glycinate chelate. Regression analysis indicated that absorption of both sources of iron were similarly regulated by the body according to changes in hemoglobin. We concluded that ferrous bis-glycinate chelate is the iron of choice for the treatment of infants with iron-defciency anemia because of its high bioavailability and good regulation.

Pineda O, Ashmead HD. Effectiveness of treatment of iron-deficiency anemia in infants and young children with ferrous bis-glycinate chelate. Nutrition. 2001 May;17(5):381-4. doi: 10.1016/ s0899-9007(01)00519-6. PMID: 11377130. TITLE: RELATIVE EFFECTIVENESS OF IRON BIS-GLYCINATE CHELATE (FERROCHEL) AND FERROUS SULFATE IN THE CONTROL OF IRON DEFICIENCY IN PREGNANT WOMEN

Abstract The relative effectiveness of daily supplementation of iron defciency during pregnancy using 15 mg/day of iron from iron-bis-glycinate chelate (71 pregnant women), or 40 mg iron from ferrous sulfate (74 pregnant women) was evaluated by measuring hemoglobin, transferrin saturation and serum ferritin, at the beginning of the study (< 20 weeks of pregnancy) and at 20-30 weeks and 30-40 weeks thereafter. Ingestion for 13 weeks or more was considered adequate. Seventy three percent of the Ferrochel consuming group and 35% of the ferrous sulfate consuming group were considered to have taken the treatment adequately. The decrease in levels of all the measured parameters was signifcantly less pronounced in the group that consumed Ferrochel in spite of the lower treatment dose. Iron depletion was found in 30.8% of the women treated with Ferrochel and in 54.5% of the women than consumed ferrous sulfate. Of the factors responsible for non compliance taste was reported in 29.8% of the ferrous sulfate consumers and none in the groups that consumed Ferrochel. It is concluded that daily supplementation with Ferrochel was signifcantly more effective, in spite of the lower dose, than supplementation with ferrous sulfate.

Szarfarc SC, de Cassana LM, Fujimori E, Guerra-Shinohara EM, de Oliveira IM. Relative effectiveness of iron bis-glycinate chelate (Ferrochel) and ferrous sulfate in the control of iron deficiency in pregnant women. Arch Latinoam Nutr. 2001 Mar;51(1 Suppl 1):42-7. PMID: 11688081. TITLE: EFFECTS OF MAGNESIUM CITRATE, MAGNESIUM OXIDE AND MAGNESIUM SULFATE SUPPLEMENTATION ON ARTERIAL STIFFNESS IN HEALTHY OVERWEIGHT INDIVIDUALS: A STUDY PROTOCOL FOR A RANDOMIZED CONTROLLED TRIAL

Abstract

Background: Arterial stiffness is closely related to the process of atherosclerosis, an independent cardiovascular risk factor, and predictive of future cardiovascular events and mortality. Recently, we showed that magnesium citrate supplementation results in a clinically relevant improvement of arterial stiffness. It remained unclear whether the observed effect was due to magnesium or citrate, and whether other magnesium compounds may have similar effects. Therefore, we aim to study the long-term effects of magnesium citrate, magnesium oxide and magnesium sulfate on arterial stiffness. In addition, we aim to investigate possible underlying mechanisms, including changes in blood pressure and changes in gut microbiota diversity.

Discussion: The present study is expected to provide evidence for the effects of different available magnesium formulations (organic and inorganic) on well-established cardiovascular risk markers, including arterial stiffness and blood pressure, as well as on the human gut microbiota. As such, the study may contribute to the primary prevention of cardiovascular disease in slightly obese, but otherwise healthy, individuals.

Schutten JC, Joris PJ, Mensink RP, et al. Effects of magnesium citrate, magnesium oxide and magnesium sulfate supplementation on arterial stiffness in healthy overweight individuals: a study protocol for a randomized controlled trial. Trials. 2019;20(1):295. Published 2019 May 28. doi:10.1186/ s13063-019-3414-4

COLLAGEN PROTEIN

! Largest Protein in our body. 65% of our total protein. ! Collagen Protein make up heart, lungs, blood vessels, discs, muscle, bone, internal organs. ! Ptosis = loss of collagen, droopy organs and skin. Caused by hormonal changes, drugs alcohol ,processed foods, white sugar, hydrogenated oils, fluoridated water, dehydration, stress, and trauma. COLLAGEN TYPES

▪ Several different types of protein have been identified, but most of the collagen in the body is type I, II, or III. ▪ Type I- The most common and is distributed in the bones, teeth, ligaments, and tendons. It is also present in skin and is responsible for the skins elasticity and strength. (Wrinkles & aged appearance.) ▪ Source: Bovine- Organic Grass Fed ▪ Type II- Cartilage ▪ Source: Chicken or Hooves of GMO Fed Cows ▪ Type III- Most prevalent in skin, blood vessels, and internal organs. ▪ Source: Caged GMO Fed Chicken Feet

León-López, Arely et al. “Hydrolyzed Collagen-Sources and Applications.” Molecules (Basel, Switzerland) vol. 24,22 4031. 7 Nov. 2019, doi:10.3390/molecules24224031 WHY HYDROLYZED COLLAGEN TYPE 1 ?

!The body can’t absorb collagen in whole form. !This protein must be broken down during the digestive process before it can be absorbed. !To increase bioavailability we use Hydrolyzed collagen ! Collagens long amino acid chain is broken down into peptides (about 2-3 amino acids together) ! = Much easier absorption process for the GI tract, capsules are better than powder no clumping.

León-López, Arely et al. “Hydrolyzed Collagen-Sources and Applications.” Molecules (Basel, Switzerland) vol. 24,22 4031. 7 Nov. 2019, doi:10.3390/molecules24224031 PROCESS OF ENZYMATIC HYDROLYSIS

Definition: Catalytic decomposition of a chemical compound by reaction with water.

In supplements it is used for the breakdown of proteins into amino acids by the addition of the enzyme protease. HYDROLYZED COLLAGEN TYPE 1

! Results ! Lean Muscle, muscle tone, skin tone, joint rebuilding, stronger arteries, increased energy, and organ rebuilding. ! Long Term Improvements in: ! Osteoporosis, high blood pressure, arthritis, weak bladder, obesity, chronic fatigue, and autoimmune diseases.

SEQUENTIAL EXTRACTION OF GEL FORMING PROTEINS, COLLAGEN AND COLLAGEN HYDROLYSATE FROM GUTTED SILVER CARP (HYPOPHTHALMICHTHYS MOLTRIX) A BIOREFINERY APPROACH

! Collagen and collagen hydrolysate (CH) was recovered from the bone and skin containing sediment residue emerging during pH-shift-based protein isolation from silver carp. Hydrolysis resulted in higher yield (15.1-15.4%) compared to collagen isolation by acid or pepsin (3.1-5.9%) (p<0.05). Isolated collagens were characterized as type I and maintained their triple-helical structure, confirmed by SDS-PAGE and FTIR. Pepsin-hydrolysis and sequential hydrolysis by pepsin and trypsin hydrolyzed all heavy molecular weight chains of collagen but sequential hydrolysis yielded higher degree of hydrolysis. When CH was added to a silver carp protein isolate prior to gelation, the gel behavior was dependent on molecular weight of the added CH. More hydrolyzed collagen emerging from sequential hydrolysis improved water holding capacity of the gel while reducing its breaking force. Thus, residue from pH-shift processing of fish can be used for isolation of high quality collagen/CH and provides a promising basis for a multiple-product fish biorefinery.

Food Chem. 2018 Mar 1;242:568-578. doi: 10.1016/ j.foodchem.2017.09.045. Epub 2017 Sep 11. DAILY ORAL CONSUMPTION OF HYDROLYZED TYPE 1 COLLAGEN IS CHONDROPROTECTIVE AND ANTI- INFLAMMATORY IN MURINE POST TRAUMATIC OSTEOARTHRITIS.

Osteoarthritis (OA) is a degenerative joint disease for which there are no disease modifying therapies. Thus, strategies that offer chondroprotective or regenerative capability represent a critical unmet need. Recently, oral consumption of a hydrolyzed type 1 collagen(hCol1) preparation has been reported to reduce pain in human OA and support a positive influence on chondrocyte function. To evaluate the tissue and cellular basis for these effects, we examined the impact of orally administered hCol1 in a model of posttraumatic OA (PTOA). In addition to standard chow, male C57BL/6J mice were provided a daily oral dietary supplement of hCol1 and a meniscal-ligamentous injury was induced on the right knee. At various time points post-injury, hydroxyproline (hProline) assays were performed on blood samples to confirm hCol1 delivery, and joints were harvested for tissue and molecular analyses were performed, including histomorphometry, OARSI and synovial scoring, immunohistochemistry and mRNA expression studies. Confirming ingestion of the supplements, serum hProline levels were elevated in experimental mice administered hCol1. In the hCol1 supplemented mice, chondroprotective effects were observed in injured knee joints, with dose-dependent increases in cartilage area, chondrocyte number and proteoglycan matrix at 3 and 12 weeks post-injury. Preservation of cartilage and increased chondrocyte numbers correlated with reductions in MMP13 protein levels and apoptosis, respectively. Supplemented mice also displayed reduced synovial hyperplasia that paralleled a reduction in Tnf mRNA, suggesting an anti-inflammatoryeffect. These findings establish that in the context of murine knee PTOA, daily oral consumption of hCol1 is chondroprotective, anti-apoptotic in articular chondrocytes, and anti-inflammatory. While the underlying mechanism driving these effects is yet to be determined, these findings provide the first tissue and cellular level information explaining the already published evidence of symptom relief supported by hCol1 in human knee OA. These results suggest that oral consumption of hCol1 is disease modifying in the context of PTOA.

PLoS One. 2017 Apr 6;12(4):e0174705. doi: 10.1371/journal.pone.0174705. eCollection 2017. COMING SOON!

Type One Collagen Face Cream ARTICLE TITLE: TOPICAL SKIN THERAPIES IN SUBJECTS UNDERGOING FULL FACIAL REJUVENATION.

DATE & JOURNAL: J COSMET DERMATOL. 2019 APR 29.

!BACKGROUND: Cosmeceutical therapies including face washes, moisturizers, chemical peels and antioxidant formulations are intended to improve the esthetic appearance of skin. The use of these products as adjuncts to full facial rejuvenation with hyaluronic acid filler and abobotulinumtoxinA may improve cosmetic and socio-esthetic outcomes.

!OBJECTIVE: To characterize the effect of skin care products in subjects undergoing full facial rejuvenation with abobotulinumtoxinA and hyaluronic acid in improving facial skin appearance, patient satisfaction, and projected first impressions.

!METHODS: Twenty subjects were recruited and divided into two treatment groups. Subjects in Group A followed a standard skin care regimen, whereas subjects in Group B received a more robust skin care regimen including chemical peels and antioxidant formulations. All subjects underwent facial rejuvenation treatments with hyaluronic acid at Visit 2 and with abobotulinumtoxinA at Visit 7. Patient esthetic improvement, satisfaction, self-esteem, and first impression were evaluated via the Fitzpatrick Wrinkle Assessment Scale, Global Aesthetic Improvement Scale, Skin Quality Assessment, Heatherton & Polivy State Self-Esteem Scale, Subject Satisfaction Scale, and the First Impressions Questionnaire.

!RESULTS: Both treatment groups experienced significant improvements in the Skin Quality Assessment, Fitzpatrick Wrinkle Assessment Scale, Heatherton and Polivy State Self-Esteem Scale, and First Impressions Questionnaire.

!CONCLUSION: The cosmeceutical therapies used in this study in combination with abobotulinumtoxinA and hyaluronic acid filler improved subjects' skin quality, self-esteem, and projected first impressions. Larger studies are needed to determine the most efficacious combination of topical skin therapies with facial rejuvenation therapy. ARTICLE TITLE: HYALURONIC ACID-CROSS-LINKED FILLER STIMULATES COLLAGEN TYPE 1 AND ELASTIC FIBER SYNTHESIS IN SKIN THROUGH THE TGF-Β/SMAD SIGNALING PATHWAY IN A NUDE MOUSE MODEL.

DATE & JOURNAL: J PLAST RECONSTR AESTHET SURG. 2019 APR 11

! Compared to pure hyaluronic acid filler, cross-linked hyaluronic acid (HAc) exhibits superior biocompatibility and longevity as a dermal filler. We previously developed composite HAc- hydroxyapatite (HAp) fillers. Herein, we systematically compared the protein-level increase and gene expression between HAc-micro-HAp and HAc-nano-HAp in mice and determined the mechanisms underlying the biological responses to HAc and HAp. Five-week-old female BALB/c-nude mice were classified into five groups: normal skin, Radiesse, Restylane, HAc-nano-HAp, and HAc-micro-HAp. Fillers (200 µl) were injected to evenly fill the back of mice. Skin biopsies were performed to investigate collagen and elastic fiber synthesis after filler injections. Western blot analysis, real-time polymerase chain reaction analysis, and immunohistochemistry were performed to investigate protein and gene expression changes. Organ (liver, lung, spleen, and kidney) toxicity of HAc-nano-HAp was determined by hematoxylin and eosin staining after 12 weeks. Protein and gene expression analyses indicated that, compared with pure fillers, HAc-nano-HAp and HAc-micro-HAp hydrogels preferentially promoted collagen and elastic fiber formation through the TGF-β pathway. The composite fillers also exhibited no evidence of organ toxicity. HAc-HAp filler might play an important role in collagen and elastic fiber regeneration. HAc filler stimulates collagen type 1 and elastic fiber synthesis through the TGF-β/Smad pathway. The role of HAc-HAp composite fillers in photoaging in animal models and their effects on skin, including elasticity and tensile strength, should be investigated. ARTICLE TITLE: HYALURONIC ACID, A PROMISING SKIN REJUVENATING BIOMEDICINE: A REVIEW OF RECENT UPDATES AND PRE-CLINICAL AND CLINICAL INVESTIGATIONS ON COSMETIC AND NUTRICOSMETIC EFFECTS.

DATE & JOURNAL: INT J BIOL MACROMOL. 2018 DEC

! Hyaluronic acid (HA) plays multifaceted role in regulating the various biological processes such as skin repairmen, diagnosis of cancer, wound healing, tissue regeneration, anti-inflammatory, and immunomodulation. Owing to its remarkable biomedical and tissue regeneration potential, HA has been numerously employed as one of the imperative components of the cosmetic and nutricosmetic products. The present review aims to summarize and critically appraise recent developments and clinical investigations on cosmetic and nutricosmetic efficacy of HA for skin rejuvenation. A thorough analysis of the literature revealed that HA based formulations (i.e., gels, creams, intra-dermal filler injections, dermal fillers, facial fillers, autologous fat gels, lotion, serum, and implants, etc.) exhibit remarkable anti-wrinkle, anti-nasolabial fold, anti-aging, space-filling, and face rejuvenating properties. This has been achieved via soft tissue augmentation, improved skin hydration, collagen and elastin stimulation, and face volume restoration. HA, alone or in combination with lidocaine and other co-agents, showed promising efficacy in skin tightness and elasticity, face rejuvenation, improving aesthetic scores, reducing the wrinkle scars, longevity, and tear trough rejuvenation. Our critical analysis evidenced that application/administration of HA exhibits outstanding nutricosmetic efficacy and thus is warranted to be used as a prime component of cosmetic products. COLON HEALTH.

This Photo by Unknown Author is licensed under CC BY-SA We kill our friendly bacteria from an acidic diet. COLON Acidification of the CLEANSING: body decreases WHY THE enzyme production. Mucoid plaque from NEED rotting food in the intestinal lining halts peristalsis. TRANSIT TIME= 3 MEALS ONLY

! Transit time: We’re only supposed to store three meals before a meal comes out(Jensen), but most Americans store nine, twelve, or even more. ! This increased transit time is irritating to the intestinal lining. We absorb less and less nutrients and we lose more and more water and minerals. COLON CLEANSING PROTOCOL IN CHILDREN: RESEARCH CONDITIONS VS. CLINICAL PRACTICE

!BACKGROUND AND STUDY AIMS: Colon preparation rates are the limiting factor for a successful diagnostic colonoscopy in children. Different colon cleansing protocols have been published for use in children. Unfortunately, the applicability of those published research protocols has not been formally evaluated in routine clinical practice. We investigated the success rate of our previously published colon cleansing protocol as utilized in our clinical practice.

!RESULTS:The success rate of the colon preparation in our clinical practice was similar to the results observed under our research protocol (75 % vs. 73.6 %). Moreover, the total number of stools, stool consistency, and the intubation rate of the terminal ileum were also similar. We concluded, that in our experience, the colon cleansing protocol used under research conditions was effective and appropriate for use in routine clinical practice.

!CONCLUSION:We recommend testing each new protocol under the routine conditions of clinical practice to confirm its applicability for general practitioners.

Endosc Int Open. 2018 Apr;6(4):E410-E413. doi: 10.1055/s-0043-121985. Epub 2018 Mar 29. THE COLON REVISITED OR THE KEY TO WELLNESS, HEALTH AND DISEASE.

The hypothesis being advanced in this paper is that there is a new medical paradigm emerging from the biomedical research carried out in this century, mainly due to the explosion of the so called "omics" and associated techniques. The main idea is that there is a common pathway from wellbeing and health to chronic disease ("chronopathy") and even to death, which comprises following steps: 1) unhealthy diet, sedentary life style and permanent exposition to xenobiotics and all kinds of noxious stimuli;→2) intestinal dysbiosis;→3) alteration of the intestinal mucus layer (especially that of the colon);→4) disruption of the endothelial tight junctions;→5) metabolic endotoxemia+bacterial translocation;→6) inflammation;→7) exacerbation of the enteric nervous system (ENS) and consequent maladaptation and malfunctioning of the colon;→8) epigenetic manifestations;→9) "chronopathy" and premature death. Therefore, in order to maintain a good health or to improve or even reverse chronic diseases in a person, the main outcome to look for is a homeostatic balance of the intestinal microbiota (eubiosis), most of which is located in the colon. Lynn Margulis was one of the main scientists to highlight the importance of the role played by bacteria not only in the origin of all biological species now present on earth, but also on their role in global homeostasis. Bacteria do not rely on other living beings for their existence, while the latter depend completely on the former. Humans are no exemption, and new evidence emerges each day about the pivotal role of intestinal microbiota in human health, disease and, in general, in its wellbeing. The following facts about intestinal microbiota are nowadays generally accepted: there are about 10 times more bacteria in the gut than human cells in every human being; the microbioma is about 100150 times bigger that the human genome, and there is a clear link between intestinal microbiota and many of the most common chronic diseases, from obesity and diabetes to depression and Parkinson disease and different kinds of cancer. The main implication of this theory is that we should become a sort of microbiota farmers, that is, we ought to be more conscious of our intestinal microbiota, take care of it and monitor it permanently. Thus, as part of our good life habits (healthy eating, physical exercise), we should probably undergo periodic seasons of fasting and colon cleansing, as it was common in older times.

Med Hypotheses. 2017 Oct;108:133143. doi: 10.1016/j.mehy.2017.07.032. Epub 2017 Jul 29. DIVERTICULITIS:Curr Probl Surg . 2020 Oct AN UPDATE FROM THE AGE OLD PARADIGM

Abstract:LINK: HTTPS://PUBMED.NCBI.NLM.NIH.GOV/33077029/ For a disease process that affects so many, we continue to struggle to define optimal care for patients with diverticular disease. Part of this stems from the fact that diverticular disease requires different treatment strategies across the natural history- acute, chronic and recurrent.

To understand where we are currently, it is worth understanding how treatment of diverticular disease has evolved. Diverticular disease was rarely described in the literature prior to the 1900’s. In the late 1960’s and early 1970’s, Painter and Burkitt popularized the theory that diverticulosis is a disease of Western civilization based on the observation that diverticulosis was rare in rural Africa but common in economically developed countries. Previous surgical guidelines focused on early operative intervention to avoid potential complicated episodes of recurrent complicated diverticulitis (e.g., with free perforation) that might necessitate emergent surgery and stoma formation. More recent data has challenged prior concerns about decreasing effectiveness of medical management with repeat episodes and the notion that the natural history of diverticulitis is progressive. It has also permitted more accurate grading of the severity of disease and permitted less invasive management options to attempt conversion of urgent operations into the elective setting, or even avoid an operation altogether. The role of diet in preventing diverticular disease has long been debated. A high fiber diet appears to decrease the likelihood of symptomatic diverticulitis. The myth of avoid eating nuts, corn, popcorn, and seeds to prevent episodes of diverticulitis has been debunked with modern data. Overall, the recommendations for “diverticulitis diets” mirror those made for overall healthy lifestyle – high fiber, with a focus on whole grains, fruits and vegetables.

Diverticulosis is one of the most common incidental findings on colonoscopy and the eighth most common outpatient diagnosis in the United States. Over 50% of people over the age of 60 and over 60% of people over age 80 have colonic diverticula. Of those with diverticulosis, the lifetime risk of developing diverticulitis is estimated at 10–25%, although more recent studies estimate a 5% rate of progression to diverticulitis. Diverticulitis accounts for an estimated 371,000 emergency department visits and 200,000 inpatient admissions per year with annual cost of 2.1–2.6 billion dollars per year in the United States. The estimated total medical expenditure (inpatient and outpatient) for diverticulosis and diverticulitis in 2015 was over 5.4 billion dollars. The incidence of diverticulitis is increasing. Hawkins AT, Wise PE, Chan T, Lee JT, Glyn T, Wood V, Eglinton T, Frizelle F, Khan A, Hall J, Ilyas MIM, Michailidou M, Nfonsam VN, Cowan ML, Williams J, Steele SR, Alavi K, Ellis CT, Collins D, Winter DC, Zaghiyan K, Gallo G, Carvello M, Spinelli A, Lightner AL. Diverticulitis: An Update From the Age Old Paradigm. Curr Probl Surg. 2020 Oct;57(10):100862. doi: 10.1016/j.cpsurg.2020.100862. Epub 2020 Jul 18. PMID: 33077029; PMCID: PMC7575828. CONTINUED: DIVERTICULITIS: AN UPDATE FROM THE AGE OLD PARADIGM Abstract Continued:

Besides increasing age, other risk factors for diverticular disease include use of NSAIDS, aspirin, steroids, opioids, smoking and sedentary lifestyle. Diverticula most commonly occur along the mesenteric side of the antimesenteric taeniae resulting in parallel rows. These spots are thought to be relatively weak as this is the location where vasa recta penetrate the muscle to supply the mucosa. The exact mechanism that leads to diverticulitis from diverticulosis is not definitively known.

The most common presenting complaint is of left lower quadrant abdominal pain with symptoms of systemic unwellness including fever and malaise, however the presentation may vary widely. The gold standard cross-sectional imaging is multi- detector CT. It is minimally invasive and has sensitivity between 98% and specificity up to 99% for diagnosing acute diverticulitis. Uncomplicated acute diverticulitis may be safely managed as an out-patient in carefully selected patients. Hospitalization is usually necessary for patients with immunosuppression, intolerance to oral intake, signs of severe sepsis, lack of social support and increased comorbidities. The role of antibiotics has been questioned in a number of randomized controlled trials and it is likely that we will see more patients with uncomplicated disease treated with observation in the future. Acute diverticulitis can be further sub classified into complicated and uncomplicated presentations. Uncomplicated diverticulitis is characterized by inflammation limited to colonic wall and surrounding tissue. The management of uncomplicated diverticulitis is changing. Use of antibiotics has been questioned as it appears that antibiotic use can be avoided in select groups of patients. Surgical intervention appears to improve patient’s quality of life. The decision to proceed with surgery is recommended in an individualized manner.

Complicated diverticulitis is defined as diverticulitis associated with localized or generalized perforation, localized or distant abscess, fistula, stricture or obstruction. Abscesses can be treated with percutaneous drainage if the abscess is large enough. The optimal long-term strategy for patients who undergo successful non-operative management of their diverticular abscess remains controversial. There are clearly patients who would do well with an elective colectomy and a subset who could avoid an operation all together however, the challenge is appropriate risk-stratification and patient selection. Management of patients with perforation depends greatly on the presence of feculent or purulent peritonitis, the extent of contamination and hemodynamic status and associated comorbidities. Fistulas and strictures are almost always treated with segmental colectomy.

View Article via Link to Continue: Link: https://pubmed.ncbi.nlm.nih.gov/33077029/

Hawkins AT, Wise PE, Chan T, Lee JT, Glyn T, Wood V, Eglinton T, Frizelle F, Khan A, Hall J, Ilyas MIM, Michailidou M, Nfonsam VN, Cowan ML, Williams J, Steele SR, Alavi K, Ellis CT, Collins D, Winter DC, Zaghiyan K, Gallo G, Carvello M, Spinelli A, Lightner AL. Diverticulitis: An Update From the Age Old Paradigm. Curr Probl Surg. 2020 Oct;57(10):100862. doi: 10.1016/j.cpsurg.2020.100862. Epub 2020 Jul 18. PMID: 33077029; PMCID: PMC7575828. LOW COMPLEXITY MICROBIOTA IN THE DUODENUM OF CHILDREN WITH NEWLY DIAGNOSED ULCERATIVE COLITIS.

BACKGROUND: Inflammatory bowel disease (IBD) is characterized by gut dysbiosis. To date, the large bowel microbiota has been in focus. However, the microbiota of the small intestine may also be of importance, as the small bowel is a site for the induction and control of mucosal immune responses, which can be modulated by constituents of the local microbiota. METHODS: Duodenal fluids were collected during diagnostic workup of treatment naïve children who were suspected of having IBD. The duodenal fluids were analyzed by pyrosequencing (average of 32,000 reads/sample, read length of 500 nucleotides). After diagnosis, the duodenal microbiota of subjects with ulcerative colitis (N = 8) or Crohn's disease (N = 5), and nonIBD controls (N = 8) were compared. RESULTS: Pyrosequencing revealed that the duodenal microbiota of children with ulcerative colitis contained fewer Operational Taxonomic Units (OTUs) per individual than the duodenal microbiota of the controls (P = 0.005). This reduction in richness of the duodenal microbiota was seen for three major phyla: Firmicutes, Actinobacteria, and Bacteroidetes. Several bacterial genera were detected less frequently in the children with ulcerative colitis than in the nonIBD controls, including Collinsella (P = 0.001), Lactobacillus (P = 0.007), and Bacillus (P = 0.007), as well as a nonidentified member of the order Sphingobacteriales (P = 0.007). CONCLUSIONS: In this pilot study, we show that the duodenal microbiota of children with ulcerative colitis exhibits reduced overall richness, despite the fact that the inflammation is primarily localized to the colon. These results should be corroborated in a larger study.

PLoS One. 2017 Oct 19;12(10):e0186178. doi: 10.1371/journal.pone.0186178. eCollection 2017. NUTRITION

WATER pH, Ionization, Molecular size Filtration and nutritional benefits Lab Testing of bottled waters for pH & safety MOLECULAR HYDROGEN

!The chemical formula H2 –composed of two bonded hydrogen atoms and is the smallest molecule in existence. !The size enables molecular hydrogen to be dispersed readily in the body and cross through the blood/brain barrier. MOLECULAR HYDROGEN BENEFITS

!Reducing inflammation

!pain relief

!pain in joints

!Decelerating the aging process !Decreasing muscle fatigue WATER & CONSTIPATION

!Up to one half of all Americans have it. !Drinking Chlorinated water = Constipation ! Chlorine compounds in tap water kill the helpful good gut bacteria, leading to overgrowth of harmful bacteria, yeasts, or even parasites.

1. Igram C, Igram C, Igram C. How To Eat Right And Live Longer. Buffalo Grove, IL: Knowledge House Publishers; 2005. h.molecularhydrogenfoundation.org/studies/ IS IONIZED WATER THE SAME AS MOLECULAR HYDROGEN WATER?

!Yes! - The ionizer machine uses your water from the tap to be hydrogen- rich alkaline water using a system of filtration and ionization. !Example- ACE-13 & UCE-11 have a revolutionary Extreme Molecular hydrogen boost technology that maximizes the hydrogen and antioxidant output.

HOW MUCH WATER SHOULD WE DRINK?-HALF YOUR BODY WEIGHT IN OZ. PER DAY (MINIMUM!)

Hydration usually takes about 8 weeks to achieve if drinking the proper amount. WHAT TO LOOK FOR IN WATER SYSTEMS

!Filtration (Carbon Ceramic Fiber Filter) !Being able to control the pH/acid/alkalinity !Number of plates in the machine (9-13 preferred) !Less molecules per cluster !Self Cleaning !No adding of minerals !Lifetime Warranty ALKALINE H2 HYBRID Above counter with SUPERCHARGED Xtreme

• First ever alkaline hydrogen hybrid water ionizer

• Supercharged Xtreme Molecular Hydrogen Boost • New Twin Cell Technology • Touchscreen • TM Ceramic & Carbon Block filtration EDGE 9000 With Molecular Hydrogen Boost

• Auto fill Quantity Selector

• 3 Alkaline Levels and 3 Acidic Levels – Plus Turbo Modes • Outstanding Electrolysis • Smartphone Touch Technology • TM Ceramic & Carbon Block filtration • Benefits of Acidic Water: ACIDIC • Natural astringent & skin WATER cleanser • Helps clear up bacteria that SKIN & HAIR causes acne • Soothes the itch & sting of ARE insect bites, eczema & BETWEEN 4.5 psoriasis • Removes tooth plaque TO 5.5 PH • Improves plant growth NUTRITION

IMMUNE SYSTEM RESEARCH Resent studies from the NIH/PubMed

Corona Virus Literature TITLE: SELENIUM AND AUTOIMMUNE DISEASES: A REVIEW ARTICLE Abstract

Background: Selenium is an essential trace element with fundamental effects on human biology. Trace elements deficiency is not an uncommon finding in autoimmune diseases. This deficiency may be a consequence of autoimmune diseases or may contribute to their etiology. With regard to evidence showing the association between selenium deficiency and generation of reactive oxygen species and subsequent inflammation, reviewing the role of selenium in collagen vascular diseases could help researchers to devise strategies for managing these diseases.

Objective: The present study aimed to evaluate the role of selenium and autoimmune rheumatic diseases.

Study eligibility criteria: All the studies on the use of selenium without any limitations in terms of the preparation method, administration route, or formulation process were included in the study. The exclusion criteria were: 1) Articles published in languages other than English, 2) Administration of chemical and hormonal drugs rather than selenium, 3) Investigation of the effects of selenium on the autoimmune problems in animal models, and 4) Insufficiency of the presented data or poor description of the applied methods. Furthermore, review articles, meta-analyses, expert opinions, editorial letters, case reports, consensus statements, and qualitative studies were excluded from the study. Sahebari M, Rezaieyazdi Z, Khodashahi M. Selenium and Autoimmune Diseases: A Review Article. Curr Rheumatol Rev. 2019;15(2):123-134. doi:10.2174/1573397114666181016112342 TITLE: SELENOMETHIONINE RELIEVES INFLAMMATION IN THE CHICKEN TRACHEA CAUSED BY LPS THOUGH INHIBITING THE NF-ΚB PATHWAY

Abstract

Selenomethionine is able to relieve the effect of inflammation in various tissues and organs. However, there are few studies about the influences of organic selenium resisting inflammation induced by LPS in chicken trachea. Therefore, the purpose of this experiment is to explore the organic selenium (selenomethionine) can raise immune function and relieve the LPS- induced inflammation of chicken trachea via inhibiting the NF-κB pathway. To investigate the mechanism of organic selenium on chicken trachea, the supplement of selenomethionine and/or LPS-induced chicken models were established. One hundred 46-week-old isa chickens were randomly divided into four groups (n = 25). The four groups were the control group, the selenomethionine group (Se group), the LPS-induced group (LPS group), and the Se and LPS interaction group (Se + LPS group). Then, the expressions of inflammatory factors (including induced nitric oxide synthase (iNOS), nuclear factor-kappa B(NF-κB), tumor necrosis factor (TNF-α), cyclooxygenase-2 (COX-2), and prostaglandin E (PTGEs) synthase), inflammation-related cytokines (including interleukin (IL-2, IL-6, IL-8, IL-17) and immunoglobulin (IgA, IgM, IgY)), the marker of immune function (avian β-defensins (AvBD6, AvBD7)), heat shock proteins (including HSP60, HSP90), and selenoproteins (including Selo, Sels, Selm, Selh, Selu, Seli, SPS2, GPx1, GPx2, Dio1, Sepx1, Sep15, Sepp1, Txnrd1) were detected in our experiment. The above genes were significantly changed in different groups (p < 0.05). We can conclude that organic selenium can increase the function of immunity and the expression of selenoproteins, and mitigate the inflammation induced by LPS via suppression of the NF-κB pathway.

Shi X, Wang W, Zheng S, Zhang Q, Xu S. Selenomethionine relieves inflammation in the chicken trachea caused by LPS though inhibiting the NF-κB pathway. Biol Trace Elem Res. 2020;194(2):525-535. doi:10.1007/s12011-019-01789-1 TITLE: SELENOMETHIONINE SUPPLEMENTATION REDUCES LESION BURDEN, IMPROVES VESSEL FUNCTION AND MODULATES THE INFLAMMATORY RESPONSE WITHIN THE SETTING OF ATHEROSCLEROSIS

Abstract

Atherosclerosis is a chronic inflammatory disease of the vasculature characterised by the infiltration of activated neutrophils and macrophages at sites of damage within the vessel wall, which contributes to lesion formation and plaque progression. Selenomethionine (SeMet) is an organic form of selenium (Se), an essential trace element that functions in the regulation of the immune response by both bolstering the endogenous thioredoxin and glutathione antioxidant defence systems and by directly scavenging damaging oxidant species. This study evaluated the effect of dietary SeMet supplementation within a high fat diet fed apolipoprotein E deficient (ApoE-/-) mouse model of atherosclerosis. Dietary supplementation with SeMet (2 mg/kg) increased the tissue concentration of Se, and the expression and activity of glutathione peroxidase, compared to non-supplemented controls. Supplementation with SeMet significantly reduced atherosclerotic plaque formation in mouse aortae, resulted in a more stable lesion phenotype and improved vessel function. Concurrent with these results, SeMet supplementation decreased lesion accumulation of M1 inflammatory type macrophages, and decreased the extent of extracellular trap release from phorbol myristate acetate (PMA)-stimulated mouse bone marrow-derived cells. Importantly, these latter results were replicated within ex-vivo experiments on cultured neutrophils isolated from acute coronary syndrome patients, indicating the ability of SeMet to alter the acute inflammatory response within a clinically-relevant setting. Together, these data highlight the potential beneficial effect of SeMet supplementation as a therapeutic strategy for atherosclerosis.

Zhang Y, Cartland SP, Henriquez R, et al. Selenomethionine supplementation reduces lesion burden, improves vessel function and modulates the inflammatory response within the setting of atherosclerosis. Redox Biol. 2020;29:101409. doi:10.1016/j.redox.2019.101409 TITLE: DOES LARCH ARABINOGALACTAN ENHANCE IMMUNE FUNCTION? A REVIEW OF MECHANISTIC AND CLINICAL TRIALS

Abstract

The common cold is a viral infection with important economic burdens in Western countries. The research and development of nutritional solutions to reduce the incidence and severity of colds today is a major focus of interest, and larch arabinogalactan seems to be a promising supportive agent. Arabinogalactan has been consumed by humans for thousands of years and is found in a variety of common vegetables as well as in medicinal herbs. The major commercial sources of this long, densely branched, high-molecular-weight polysaccharide are North American larch trees. The aim of this article is to review the immunomodulatory effects of larch arabinogalactan derived from Larix laricina and Larix occidentalis (North American Larix species) and more specifically its role in the resistance to common cold infections. In cell and animal models, larch arabinogalactan is capable of enhancing natural killer cells and macrophages as well as the secretion of pro-inflammatory cytokines. In humans a clinical study demonstrated that larch arabinogalactan increased the body's potential to defend against common cold infection. Larch arabinogalactan decreased the incidence of cold episodes by 23 %. Improvements of serum antigen-specific IgG and IgE response to Streptococcus pneumoniae and tetanus vaccination suggesting a B cell dependent mechanism have been reported in vaccination studies with larch arabinogalactan, while the absence of response following influenza vaccination suggests the involvement of a T cell dependent mechanism. These observations suggest a role for larch arabinogalactan in the improvement of cold infections, although the mode of action remains to be further explored. Different hypotheses can be envisaged as larch arabinogalactan can possibly act indirectly through microbiota-dependent mechanisms and/or have a direct effect on the immune system via the gut-associated lymphoid tissue (GALT).

Dion C, Chappuis E, Ripoll C. Does larch arabinogalactan enhance immune function? A review of mechanistic and clinical trials. Nutr Metab (Lond). 2016;13:28. Published 2016 Apr 12. doi:10.1186/s12986-016-0086-x TITLE: BIOACTIVITY AND POTENTIAL HEALTH BENEFITS OF LICORICE Abstract

Licorice is an herbal plant named for its unique sweet flavor. It is widely used in the food and tobacco industries as a sweetener. Licorice is also used in traditional Chinese medicine (TCM) and complementary medicine. Because the use of licorice has long been a part of TCM, the details of its therapeutic applications have been thoroughly established. In modern science, licorice is of interest because of its broad range of applications. Extracts of and compounds isolated from licorice have been well studied and biologically characterized. In this review, we discuss the nutraceutical and functional activities of licorice as well as those of the extracts of and the isolated compounds from licorice, including agents with anti-inflammatory activity, cell-protective abilities, and chemopreventive effects. The side effects of licorice are also enumerated. A comparison of the activities of licorice described by modern science and TCM is also presented, revealing the correspondence of certain characteristics.

Kao TC, Wu CH, Yen GC. Bioactivity and potential health benefits of licorice. J Agric Food Chem. 2014;62(3):542-553. doi:10.1021/jf404939f TITLE: PREVENTION AND TREATMENT OF INFLUENZA, INFLUENZA-LIKE ILLNESS, AND COMMON COLD BY HERBAL, COMPLEMENTARY, AND NATURAL THERAPIES

Abstract

In recent years viral respiratory tract infections, especially influenza viruses, have had a major impact on communities worldwide as a result of unavailability of effective treatment or vaccine. The frequent alterations in the antigenic structures of respiratory viruses, particularly for RNA viruses, pose difficulties in production of effective vaccines. The unavailability of optimal medication and shortage of effective vaccines suggests the requirement for alternative natural therapies. Several herbal remedies were used for prevention and treatment viral respiratory illnesses. Among those that were found effective included maoto, licorice roots, antiwei, North American ginseng, berries, Echinacea, plants extracted carnosic acid, pomegranate, guava tea, and Bai Shao. There is scientific evidence regarding the effectiveness of several complementary therapies for colds. Oral zinc may reduce the length and severity of a cold. Taking vitamin C supplements on a regular basis only slightly reduces the length and severity of colds. Probiotics were found better than placebo in reducing the number episodes of acute upper respiratory tract infections, the rate of episodes of acute upper respiratory tract infection and reducing antibiotic use. Alkaline diets or drinks might have antiviral properties as in vitro studies demonstrated inactivation effect of alkaline medium on respiratory virus. Earthing might have a natural anti-inflammatory effect for human body. It is now accepted that an overwhelming inflammatory response is the cause of human deaths from avian H5N1 influenza infection. Earthing accelerates immune response following vaccination, as demonstrated by increases of gamma globulin concentration. No in vivo or clinical studies were found that investigate the role of alkalization or earthing on respiratory viral infections. Thus, future studies are recommended to reveal any potential curative effects.

Mousa HA. Prevention and Treatment of Influenza, Influenza-Like Illness, and Common Cold by Herbal, Complementary, and Natural Therapies. J Evid Based Complementary Altern Med. 2017;22(1):166-174. doi:10.1177/2156587216641831 TITLE: ASTRAGALUS MEMBRANACEUS NANOPARTICLES MARKEDLY IMPROVE IMMUNE AND ANTI-OXIDATIVE RESPONSES; AND PROTECTION AGAINST AEROMONAS VERONII IN NILE TILAPIA OREOCHROMIS NILOTICUS

Abstract

The effects of dietary administration of Astragalus membranaceus nanoparticles (ANP) on immune and anti- oxidative responses, growth performance and disease resistance of Oreochromis niloticus were evaluated in the present study. Fish were divided into three groups and received the ANP at rates of 0 (control), 1, and 2%/kg diet for four weeks. After the four-week feeding trial, three fish from each replicate were sampled for immune and anti-oxidative responses evaluation, ten fish from each group were challenged with A. veronii, and nine fish from each group were subjected to cold and hypoxia challenges. It was obvious from the results that ANP significantly enhanced lysozyme activity and nitrous oxide (NO) activities, as well as improved superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities. Also, aspartate aminotransferase, alanine transaminase, glucose, and cortisol measurements showed significantly lower levels in incorporated groups compared to the control. Growth performance; and amylase and lipase digestive enzymes activities also showed markedly improved results. Expression of heat shock protein 70 (HSP70) and interleukin 1, beta (IL-1β) genes were significantly upregulated throughout the entire experimental period. When challenged with A. veronii, the mortality of treated groups was significantly (P < 0.05) lower than the control. Current results proofs that dietary ANP had a synergistic effect on immune and anti-oxidative responses, growth performance and disease resistance of Oreochromis niloticus.

Elabd H, Wang HP, Shaheen A, Matter A. Astragalus membranaceus nanoparticles markedly improve immune and anti-oxidative responses; and protection against Aeromonas veronii in Nile tilapia Oreochromis niloticus. Fish Shellfish Immunol. 2020;97:248-256. doi:10.1016/j.fsi.2019.12.025 TITLE: ASTRAGALUS POLYSACCHARIDES ENHANCE THE IMMUNE RESPONSE TO AVIAN INFECTIOUS BRONCHITIS VIRUS VACCINATION IN CHICKENS

Abstract

Astragalus polysaccharides (APS) are biological macromolecules extracted from Astragalus species that have strong immunoregulatory properties. In this study, APS were employed as an adjuvant for an avian infectious bronchitis virus (IBV) vaccine, and its effects on the cellular immune and humoral immune responses to vaccination in chicken were investigated. One hundred and fifty chicken were randomly divided into five groups (n = 30, each group). The chickens in all groups, except for the unvaccinated control group, were vaccinated with an IBV DNA vaccine. Three of the four vaccinated groups were administered different doses of APS (APSL, 10 mg/kg; APSM, 50 mg/kg; and APSH, 100 mg/kg) after the first vaccination, and the remaining vaccinated group served as a control, without any additional treatment. At 14, 28, and 42 days after the first vaccination, serum anti- IBV antibody titers; peripheral lymphocyte proliferation; and the mRNA expression of IL-1β, IL-2, IL-8, and TNF-α in the spleen were assessed by enzyme-linked immunosorbent assay (ELISA), the cell counting kit-8 (CCK-8), and real time quantitative RT-PCR (qRT-PCR), respectively. At most time points, the titer of IBV-specific antibodies, lymphocyte proliferation, and IL-1β, IL-2, IL-8, and TNF-α mRNA expression levels were higher in three APS groups than in the vaccine control group, and these increases were dose-dependent. These data suggest that APS could be used as an adjuvant for IBV vaccination to provide better protection against IBV infection.

Zhang P, Wang J, Wang W, et al. Astragalus polysaccharides enhance the immune response to avian infectious bronchitis virus vaccination in chickens. Microb Pathog. 2017;111:81-85. doi:10.1016/j.micpath.2017.08.023 TITLE : [ANTI-VIRUS RESEARCH OF TRITERPENOIDS IN LICORICE]

Abstract

Licorice is a leguminous plant of glycyrrhiza. It is a traditional Chinese herbal medicine. Triterpenoid is one of the mainly active components of licorice. In recent years, the broad-spectrum antiviral activity of many triterpenoids in licorice was confirmed, and these findings have become a hot spot of antiviral immunity. The triterpenoids of licorice has the potential to become a novel broad-spectrum antiviral medicine and will be widely used in the clinical treatment. This review provided a summary of the recent anti-virus research progress on several triterpenoids in licorice, such as glycyrrhizic acid, glycyrrhizin, glycyrrhetinic acid and its derivatives. The antiviral roles of triterpenoids in licorice against herpes virus, HIV, hepatitis virus, SARS coronavirus and influenza virus were briefly summarized.

Source: Bing Du Xue Bao. 2013 Nov;29(6):673-9. TITLE :EFFECT OF MUSHROOM AGARICUS BLAZEI ON IMMUNE RESPONSE AND DEVELOPMENT OF EXPERIMENTAL CEREBRAL MALARIA

Background: Cerebral malaria (CM) is debilitating and sometimes fatal. Disease severity has been associated with poor treatment access, therapeutic complexity and drug resistance and, thus, alternative therapies are increasingly necessary. In this study, the effect of the administration of Agaricus blazei, a mushroom of Brazilian origin in a model of CM caused by Plasmodium berghei, strain ANKA, was investigated in mice.

Results: Mice treated with A. blazei aqueous extract or fraction C, that shows antioxidant activity, displayed lower parasitaemia, increased survival, reduced weight loss and protection against the development of CM. The administration of A. blazei resulted in reduced levels of TNF, IL-1β and IL-6 production when compared to untreated P. berghei-infected mice. Agaricus blazei (aqueous extract or fraction C) treated infected mice displayed reduction of brain lesions. Although chloroquine treatment reduced parasitaemia, there was increased production of proinflammatory cytokines and damage in the CNS not observed with A. blazei treatment. Moreover, the in vitro pretreatment of infected erythrocytes followed by in vivo infection resulted in lower parasitaemia, increased survival, and little evidence of clinical signs of disease.

Conclusions: This study strongly suggests that the administration of A. blazei (aqueous extract or fraction C) was effective in improving the consequences of CM in mice and may provide novel therapeutic strategies.

Val, C.H., Brant, F., Miranda, A.S. et al. Effect of mushroom Agaricus blazei on immune response and development of experimental cerebral malaria. Malar J 14, 311 (2015). https://doi.org/10.1186/s12936-015-0832-y TITLE :LOW-MOLECULAR-WEIGHT POLYSACCHARIDES FROM AGARICUS BLAZEI MURRILL MODULATE THE TH1 RESPONSE IN CANCER IMMUNITY

Abstract

To assess the effect of low-molecular-weight polysaccharides from Agaricus blazei Murrill (ABP-AW1) as an immunoadjuvant therapy for type 1 T-helper (Th1) responses in tumorigenesis, C57BL/6 mice were inoculated subcutaneously with ovalbumin (E.G7-OVA). After 3, 10 and 17 days, the mice were immunized with PBS, OVA alone, or OVA and ABP-AW1, at low (50 µg), intermediate (100 µg) or high (200 µg) doses. Tumor growth was examined and compared among the groups, as were the following parameters: Splenocyte viability/ proliferation, peripheral blood CD4+/CD8+ T cell ratio, serum OVA-specific IgG1 and IgG2b, secretion of interleukin (IL)-2 and interferon (IFN)-γ, and IFN-γ production on a single cell level from cultured splenocytes. Tumor growth in mice treated with OVA and ABP-AW1 (100 or 200 µg) was significantly slower, compared with in the other groups at the same time-points. OVA with 100 or 200 µg ABP-AW1 was associated with a higher number of total splenocytes, a higher ratio of peripheral blood CD4+/CD8+ T-lymphocytes, higher serum levels of OVA-specific Th1-type antibody IgG2b and greater secretion of the Th1 cytokines IL-1 and IFN-γ from splenocytes. ABP-AW1 is a promising immunoadjuvant therapy candidate, due to its ability to boost the Th1 immune response when co-administered with a cancer vaccine intended to inhibit cancer progression.

Jiang L, Yu Z, Lin Y, et al. Low-molecular-weight polysaccharides from Agaricus blazei Murrill modulate the Th1 response in cancer immunity. Oncol Lett. 2018;15(3):3429-3436. doi:10.3892/ol.2018.7794 TITLE :ANTITUMOR ACTIVITY OF ORALLY ADMINISTERED MAITAKE Α-GLUCAN BY STIMULATING ANTITUMOR IMMUNE RESPONSE IN MURINE TUMOR

Abstract

Maitake α-glucan, YM-2A, isolated from Grifola frondosa, has been characterized as a highly α-1,6-branched α-1,4 glucan. YM-2A has been shown to possess an anti-virus effect in mice; however, it does not directly inhibit growth of the virus in vitro, indicating that the anti-virus effect of YM-2A might be associated with modulation of the host immune system. In this study, we found that oral administration of YM-2A could inhibit tumor growth and improve survival rate in two distinct mouse models of colon-26 carcinoma and B16 melanoma. Orally administered YM-2A enhanced antitumor immune response by increasing INF-γ-expressing CD4+ and CD8+ cells in the spleen and INF-γ-expressing CD8+ cells in tumor-draining lymph nodes. In vitro study showed that YM-2A directly activated splenic CD11b+ myeloid cells, peritoneal macrophages and bone marrow-derived dendritic cells, but did not affect splenic CD11b- lymphocytes or colon-26 tumor cells. YM-2A is more slowly digested by pancreatic α-amylase than are amylopectin and rabbit liver glycogen, and orally administered YM-2A enhanced the expression of MHC class II and CD86 on dendritic cells and the expression of MHC class II on macrophages in Peyer's patches. Furthermore, in vitro stimulation of YM-2A increased the expression of pro-inflammatory cytokines in Peyer's patch CD11c+ cells. These results suggest that orally administered YM-2A can activate dendritic cells and macrophages in Peyer's patches, inducing systemic antitumor T-cell response. Thus, YM-2A might be a candidate for an oral therapeutic agent in cancer immunotherapy.

Masuda Y, Nakayama Y, Tanaka A, Naito K, Konishi M. Antitumor activity of orally administered maitake α-glucan by stimulating antitumor immune response in murine tumor. PLoS One. 2017;12(3):e0173621. Published 2017 Mar 9. doi:10.1371/ journal.pone.0173621 TITLE :ANTIGENOTOXIC AND ANTIOXIDANT POTENTIAL OF MEDICINAL MUSHROOMS (IMMUNE ASSIST) AGAINST DNA DAMAGE INDUCED BY FREE RADICALS- AN IN VITRO STUDY

Abstract

Immune Assist (IA) is produced from extract of six species of medical mushrooms: Agaricus blazei - Cordyceps sinensis - Grifola frondosa - Ganoderma lucidum - Coriolus versicolor - Lentinula edodes. The genoprotective potential of IA was evaluated for the first time. Significant antigenotoxic effects were detected in human peripheral blood cells against H2O2 induced DNA damage, in the pretreatment and in the posttreatment. The most efficient concentration of IA in pretreatment was 500 µg/mL, while in posttreatment it was the concentration of 250 µg/mL. Kinetics of attenuation of H2O2 induced DNA damage in posttreatment with the optimal concentration of IA showed significant decrease in the number of damaged cells at all time periods (15-60 min), reaching the greatest reduction after 15 and 45 min. Remarkable ·OH scavenging properties and moderate reducing power, together with the modest DPPH scavenging activity, could be responsible for the great attenuation of DNA damage after 15 min of exposure to IA, while reduction of DNA damage after 45 min could be the result in additional stimulation of the cell's repair machinery. Our results suggest that IA displayed antigenotoxic and antioxidant properties. A broader investigation of its profile in biological systems is needed.

Živković L, Bajić V, Bruić M, et al. Antigenotoxic and antioxidant potential of medicinal mushrooms (Immune Assist) against DNA damage induced by free radicals-an in vitro study. Mutat Res. 2019;845:403078. doi:10.1016/j.mrgentox.2019.06.008 TITLE :IMPACT OF INGESTION OF RICE BRAN AND SHITAKE MUSHROOM EXTRACT ON LYMPHOCYTE FUNCTION AND CYTOKINE PRODUCTION IN HEALTHY RATS

Abstract

This article provides a controlled evaluation of the ability of dietary supplementation with a commercially available rice bran extract modified with shitake mushroom extract (MGN-3) to support the immune function by assessing the ability of immunocytes to proliferate and produce cytokines in response to a mitogenic challenge. Twenty-four male Lewis rats were fed a control diet (Maypo sweetened oatmeal) or Maypo containing the recommended daily dose of MGN-3 for 2 weeks. This treatment modestly enhanced mitogen enhanced proliferation of splenocytes and interferon-gamma (IFN-g) production, and significantly increased proliferation of splenocytes to the superantigen toxic shock syndrome toxin-1 (TSST-1) as well as natural killer (NK) cell activity and production of interleukin-2 (IL-2) by stimulated lymphocytes. These data support the contention that ingestion of MGN-3 can support immune cell function. These data add to a growing body of data showing that ingestion of MGN-3 improves the ability of immune cells to proliferate the lyse tumor cells, suggesting that it may have utility as a dietary aid to support the immune system.

Giese S, Sabell GR, Coussons-Read M. Impact of ingestion of rice bran and shitake mushroom extract on lymphocyte function and cytokine production in healthy rats. J Diet Suppl. 2008;5(1):47-61. doi:10.1080/19390210802329196 TITLE :THE EFFECT OF OLIVE LEAF EXTRACT ON UPPER RESPIRATORY ILLNESS IN HIGH SCHOOL ATHLETES: A RANDOMIZED CONTROL TRIAL

Abstract

Upper respiratory illness (URI) has a major impact on both training and competition in an athletic setting. High school athletes are a sub-category who have reported higher illness rates than professional and sub-elite high school athletes of the same sport. Olive leaf extract (OLE) is an over- the-counter supplement that contains polyphenols, notably oleuropein and hydroxytyrosol, that have antiviral, antibacterial, anti-inflammatory and antioxidant properties that may reduce URI rates. Thirty-two high school students who play sport for the elite team at their school were recruited to a randomised controlled trial and allocated to a daily placebo or OLE (extent equivalent to 20 g of olive leaf, containing 100 mg oleuropein) supplementation for nine weeks during their competitive season. Twice weekly measures of wellbeing, training load and respiratory illness (sporting upper respiratory illness (SUPPRESS) questionnaire) were recorded at trainings, meetings or games. There was no significant difference in illness incidence (odds ratio (OR): 1.02 (95% confidence interval (CI) 0.21⁻4.44)), but there was a significant 28% reduction in sick days (OR: 0.72 (95% CI 0.56⁻0.93) p-value = 0.02) when supplemented with OLE. The dietary intakes of the athletes were sub-optimal with regard to immune support. OLE supplementation over a season did not significantly reduce URI incidence, but did decrease duration in high school athletes, potentially aiding return to play.

Somerville V, Moore R, Braakhuis A. The Effect of Olive Leaf Extract on Upper Respiratory Illness in High School Athletes: A Randomised Control Trial. Nutrients. 2019;11(2):358. Published 2019 Feb 9. doi:10.3390/nu11020358 TITLE :OLIVE LEAF EXTRACTS ACT AS MODULATORS OF THE HUMAN IMMUNE RESPONSE

Abstract

Background: Olive tree leaves have been used in the Mediterranean area as traditional medicine in virtue of their healthy effects. Olive leaf extracts (OLEs) contain higher amounts of polyphenols than those detected in the extra virgin olive oil and fruit. Several lines of evidence support the cardioprotective, anti-oxidant and anti-inflammatory activities exerted by OLEs.

Results: Both extracts, but especially extract A, increased absolute numbers of CD8+ and natural killer (NK) cells. In addition, an increased production of interferon (IFN)-γ by both extracts as an expression of T helper (h)1 activation was observed. Finally, both extracts enhanced NO release.

Conclusion: OLEs, and mostly extract A, are able to in vitro modify healthy human immune response by increasing IFN- γ production which seems to be associated to the higher absolute numbers of CD8+ and NK cells and this may suggest a reinforcement of the anti-tumor activity. Furthermore, increased levels of NO may indicate the potential cardioprotective effects exerted by OLEs in virtue of their vasodilation dependent activity. Finally, OLEs are able to maintain the equilibrium between T regulatory cells and Th17 cells as evidenced by unmodified levels of interleukin (IL)- IL-10 and IL-17, respectively. In the light of these results, OLEs are potential therapeutic compounds for the treatment of chronic inflammatory disease, also preventing cardiovascular event outcome.

Magrone T, Spagnoletta A, Salvatore R, et al. Olive Leaf Extracts Act as Modulators of the Human Immune Response. Endocr Metab Immune Disord Drug Targets. 2018;18(1):85-93. doi:10.2174/1871530317666171116110537 TITLE :MULTIPLE MODULATORY ACTIVITIES OF ANDROGRAPHIS PANICULATA ON IMMUNE RESPONSES AND XENOGRAFT GROWTH IN ESOPHAGEAL CANCER PRECLINICAL MODELS

Abstract

Background: Esophageal cancer (EC) is a malignant gastrointestinal cancer with high morbidity worldwide and is the fourth leading cause of cancer-related deaths in China. Even though surgery and/or chemotherapy/chemoradiation might achieve good therapeutic response, recurrence rate is high due to cancer metastasis. Hence, the use of alternative adjuvant treatments, such as herbal medicines, for metastatic EC remains a great desire of the patients. Our previous studies have demonstrated the anti- metastatic efficacy of hot water extract of Andrographis paniculata (APW) in human esophageal cancer cells and tumor-bearing nude mice.

Conclusion: APW was shown to possess anti-tumor, anti-metastatic and immunomodulatory activities in esophageal cancer cell-based and animal models, including immunocompromised mice model and clinically relevant PDX model. Our findings illustrated the potential multi-targeted efficacies of APW in esophageal cancer management.

Yue GG, Li L, Lee JK, et al. Multiple modulatory activities of Andrographis paniculata on immune responses and xenograft growth in esophageal cancer preclinical models. Phytomedicine. 2019;60:152886. doi:10.1016/j.phymed.2019.152886 TITLE: CRITICAL CARE MANAGEMENT OF ADULTS WITH COMMUNITY-ACQUIRED SEVERE RESPIRATORY VIRAL INFECTION

Abstract

With the expanding use of molecular assays, viral pathogens are increasingly recognized among critically ill adult patients with community-acquired severe respiratory illness; studies have detected respiratory viral infections (RVIs) in 17-53% of such patients. In addition, novel pathogens including zoonotic coronaviruses like the agents causing Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and the 2019 novel coronavirus (2019 nCoV) are still being identified. Patients with severe RVIs requiring ICU care present typically with hypoxemic respiratory failure. Oseltamivir is the most widely used neuraminidase inhibitor for treatment of influenza; data suggest that early use is associated with reduced mortality in critically ill patients with influenza. At present, there are no antiviral therapies of proven efficacy for other severe RVIs. Several adjunctive pharmacologic interventions have been studied for their immunomodulatory effects, including macrolides, corticosteroids, cyclooxygenase-2 inhibitors, sirolimus, statins, anti-influenza immune plasma, and vitamin C, but none is recommended at present in severe RVIs. Evidence-based supportive care is the mainstay for management of severe respiratory viral infection. Non-invasive ventilation in patients with severe RVI causing acute hypoxemic respiratory failure and pneumonia is associated with a high likelihood of transition to invasive ventilation. Limited existing knowledge highlights the need for data regarding supportive care and adjunctive pharmacologic therapy that is specific for critically ill patients with severe RVI. There is a need for more pragmatic and efficient designs to test different therapeutics both individually and in combination.

Arabi YM, Fowler R, Hayden FG. Critical care management of adults with community-acquired severe respiratory viral infection. Intensive Care Med. 2020;46(2):315-328. doi:10.1007/s00134-020-05943-5 TITLE: PLATELET-TO-LYMPHOCYTE RATIO IS ASSOCIATED WITH PROGNOSIS IN PATIENTS WITH CORONAVIRUS DISEASE-19

Abstract

Since December 2019, novel coronavirus infected pneumonia emerged in Wuhan city and rapidly spread throughout China. In severe novel coronavirus pneumonia cases, the number of platelets, their dynamic changes during the treatment, platelet-to-lymphocyte ratio (PLR) were a concern. We sought to describe the platelet feature of these cases. Single-center case series of the 30 hospitalized patients with confirmed coronavirus disease (COVID)-19 in Huizhou municipal central hospital from January 2020 to February 2020 were retrospectively analyzed. Demographic, clinical, blood routine results, other laboratory results, and treatment data were collected and analyzed. Outcomes of severe patients and nonsevere patients were compared. Univariate analysis showed that: age, platelet peaks, and PLR at peak platelet were the influencing factors in severe patients, multivariate analysis showed that the PLR value at peak platelet during treatment was an independent influencing factor in severe patients. The average hospitalization day of patients with platelet peaks during treatment was longer than those without platelet peaks (P < .05). The average age of patients with platelet peaks during treatment was older than those without platelet peaks (P < .05). The patients with significantly elevated platelets during treatment had longer average hospitalization days. And the higher PLR of patients during treatment had longer average hospitalization days. Single-center case series of the 30 hospitalized patients with confirmed COVID-19 in Huizhou Municipal Central Hospital, presumed that the number of platelets and their dynamic changes during the treatment may have a suggestion on the severity and prognosis of the disease. The patient with markedly elevated platelets and longer average hospitalization days may be related to the cytokine storm. The PLR of patients means the degree of cytokine storm, which might provide a new indicator in the monitoring in patients with COVID-19.

Qu R, Ling Y, Zhang YH, et al. Platelet-to-lymphocyte ratio is associated with prognosis in patients with coronavirus disease-19 [published online ahead of print, 2020 Mar 17]. J Med Virol. 2020;10.1002/jmv.25767. doi:10.1002/jmv.25767 TITLE: GUIDE TO THE FORENSIC PATHOLOGY PRACTICE ON DEATH CASES RELATED TO CORONA VIRUS DISEASE 2019 （COVID-19）

Abstract

Autopsy is of great significance to the elucidation of the pathological changes, pathogeneses and causes of death of corona virus disease 2019 （COVID-19） and can provide theoretical basis for more scientific and accurate prevention and control of the outbreak. Based on related laws and regulations, such as the Law of the People's Republic of China on Prevention and Control of Infectious Diseases, the clinical manifestations and epidemiological characteristics of COVID-19, and the related guidelines on the prevention and control of the outbreak, combined with the practical work of forensic pathology examination, the Guide to the Forensic Pathology Practice on Death Cases Related to Corona Virus Disease 2019 （COVID-19） （Trial Draft） has been developed. This guide includes information on the background investigation of the cases, autopsy room requirements, personal prevention and protections, external examinations, autopsy, auxiliary examinations, and so on. This guide can be used as a reference by forensic and pathological examination institutions, as well as examination staff.

Mao DM, Zhou N, Zheng D, et al. Guide to the Forensic Pathology Practice on Death Cases Related to Corona Virus Disease 2019 （COVID-19） （Trial Draft. Fa Yi Xue Za Zhi. 2020;36(1):6-5. doi:10.12116/j.issn.1004-5619.2020.01.003 TITLE: REVIEW AND PROSPECT OF PATHOLOGICAL FEATURES OF CORONA VIRUS DISEASE

Abstract

Since 2003, coronavirus has caused multiple major public health events that resulted in global epidemics, such as severe acute respiratory syndrome （SARS）, Middle East respiratory syndrome （MERS） and corona virus disease 2019 （COVID-19）. Especially since COVID-19 outbroke in Wuhan, Hubei, in December 2019, coronavirus has had a significant impact on people's health and lives. But so far, the pathological diagnosis of COVID-19 has been relatively deficient： it is still confined to the pathological findings of punctured organs, and the majority of medical workers have poor awareness of its pathological characteristics. The COVID-19, as same as SARS and MERS, is caused by coronaviruses and can cause viral pneumonia. They have certain similarities. This article comprehensively reviews the pathological features observed in the autopsies of the aforementioned three diseases, in order to provide reference to the analysis of pathological changes of COVID-19.

Wang HJ, Du SH, Yue X, Chen CX. Review and Prospect of Pathological Features of Corona Virus Disease. Fa Yi Xue Za Zhi. 2020;36(1):16-20. doi:10.12116/ j.issn.1004-5619.2020.01.004 TITLE: THE EFFECT OF ASCORBIC ACID ON INFECTION CHICK-EMBRYO CILIATED TRACHEAL ORGAN CULTURES BY CORONAVIRUS

Abstract Chick embryo tracheal organ cultures showed increased resistance to infection by a coronavirus after exposure to ascorbate, while chick respiratory epithelium and allantois-on-shell preparations showed no increase in resistance to infection by an influenza virus or a paramyxovirus.

Atherton JG, Kratzing CC, Fisher A. The effect of ascorbic acid on infection chick- embryo ciliated tracheal organ cultures by coronavirus. Arch Virol. 1978;56(3):195- 199. doi:10.1007/BF01317848 TITLE: VITAMIN C AND SARS CORONAVIRUS

Sir,

Recently, a new coronavirus was identified as the cause of the severe acute respiratory syndrome (SARS).1 In the absence of a specific treatment for SARS, the possibility that vitamin C may show non- specific effects on severe viral respiratory tract infections should be considered. There are numerous reports indicating that vitamin C may affect the immune system,2,3 for example the function of phagocytes, transformation of T lymphocytes and production of interferon. In particular, vitamin C increased the resistance of chick embryo tracheal organ cultures to infection caused by an avian coronavirus.4 Studies in animals found that vitamin C modifies susceptibility to various bacterial and viral infections,3 for example protecting broiler chicks against an avian coronavirus.5 Placebo-controlled trials have shown quite consistently that the duration and severity of common cold episodes are reduced in the vitamin C groups,3 indicating that viral respiratory infections in humans are affected by vitamin C levels. There is also evidence indicating that vitamin C may affect pneumonia.3 In particular, three controlled trials with human subjects reported a significantly lower incidence of pneumonia in vitamin C- supplemented groups,6 suggesting that vitamin C may affect susceptibility to lower respiratory tract infections under certain conditions. The possibility that vitamin C affects severe viral respiratory tract infections would seem to warrant further study, especially in light of the recent SARS epidemic.

Hemilä H. Vitamin C and SARS coronavirus. J Antimicrob Chemother. 2003;52(6):1049-1050. doi:10.1093/jac/dkh002 TITLE: IMMUNE-ENHANCING ROLE OF VITAMIN C AND ZINC AND EFFECT ON CLINICAL CONDITIONS

Abstract

Vitamin C concentrations in the plasma and leukocytes rapidly decline during infections and stress. Supplementation of vitamin C was found to improve components of the human immune system such as antimicrobial and natural killer cell activities, lymphocyte proliferation, chemotaxis, and delayed-type hypersensitivity. Vitamin C contributes to maintaining the redox integrity of cells and thereby protects them against reactive oxygen species generated during the respiratory burst and in the inflammatory response. Likewise, zinc undernutrition or deficiency was shown to impair cellular mediators of innate immunity such as phagocytosis, natural killer cell activity, and the generation of oxidative burst. Therefore, both nutrients play important roles in immune function and the modulation of host resistance to infectious agents, reducing the risk, severity, and duration of infectious diseases. This is of special importance in populations in which insufficient intake of these nutrients is prevalent. In the developing world, this is the case in low- and middle-income countries, but also in subpopulations in industrialized countries, e.g. in the elderly. A large number of randomized controlled intervention trials with intakes of up to 1 g of vitamin C and up to 30 mg of zinc are available. These trials document that adequate intakes of vitamin C and zinc ameliorate symptoms and shorten the duration of respiratory tract infections including the common cold. Furthermore, vitamin C and zinc reduce the incidence and improve the outcome of pneumonia, malaria, and diarrhea infections, especially in children in developing countries.

Wintergerst ES, Maggini S, Hornig DH. Immune-enhancing role of vitamin C and zinc and effect on clinical conditions. Ann Nutr Metab. 2006;50(2):85-94. doi:10.1159/000090495 TITLE: VITAMIN C AND IMMUNE FUNCTION

Abstract

Vitamin C is an essential micronutrient for humans, with pleiotropic functions related to its ability to donate electrons. It is a potent antioxidant and a cofactor for a family of biosynthetic and gene regulatory enzymes. Vitamin C contributes to immune defense by supporting various cellular functions of both the innate and adaptive immune system. Vitamin C supports epithelial barrier function against pathogens and promotes the oxidant scavenging activity of the skin, thereby potentially protecting against environmental oxidative stress. Vitamin C accumulates in phagocytic cells, such as neutrophils, and can enhance chemotaxis, phagocytosis, generation of reactive oxygen species, and ultimately microbial killing. It is also needed for apoptosis and clearance of the spent neutrophils from sites of infection by macrophages, thereby decreasing necrosis/NETosis and potential tissue damage. The role of vitamin C in lymphocytes is less clear, but it has been shown to enhance differentiation and proliferation of B- and T-cells, likely due to its gene regulating effects. Vitamin C deficiency results in impaired immunity and higher susceptibility to infections. In turn, infections significantly impact on vitamin C levels due to enhanced inflammation and metabolic requirements. Furthermore, supplementation with vitamin C appears to be able to both prevent and treat respiratory and systemic infections. Prophylactic prevention of infection requires dietary vitamin C intakes that provide at least adequate, if not saturating plasma levels (i.e., 100-200 mg/day), which optimize cell and tissue levels. In contrast, treatment of established infections requires significantly higher (gram) doses of the vitamin to compensate for the increased inflammatory response and metabolic demand.

Carr AC, Maggini S. Vitamin C and Immune Function. Nutrients. 2017;9(11):1211. Published 2017 Nov 3. doi:10.3390/nu9111211 TITLE: ZINC AND IMMUNITY: AN ESSENTIAL INTERRELATION Abstract The significance of the essential trace element zinc for immune function has been known for several decades. Zinc deficiency affects immune cells, resulting in altered host defense, increased risk of inflammation, and even death. The micronutrient zinc is important for maintenance and development of immune cells of both the innate and adaptive immune system. A disrupted zinc homeostasis affects these cells, leading to impaired formation, activation, and maturation of lymphocytes, disturbed intercellular communication via cytokines, and weakened innate host defense via phagocytosis and oxidative burst. This review outlines the connection between zinc and immunity by giving a survey on the major roles of zinc in immune cell function, and their potential consequences in vivo.

Maares M, Haase H. Zinc and immunity: An essential interrelation. Arch Biochem Biophys. 2016;611:58-65. doi:10.1016/j.abb.2016.03.022 TITLE: ZINC AS A GATEKEEPER OF IMMUNE FUNCTION

Abstract

After the discovery of zinc deficiency in the 1960s, it soon became clear that zinc is essential for the function of the immune system. Zinc ions are involved in regulating intracellular signaling pathways in innate and adaptive immune cells. Zinc homeostasis is largely controlled via the expression and action of zinc "importers" (ZIP 1-14), zinc "exporters" (ZnT 1-10), and zinc-binding proteins. Anti- inflammatory and anti-oxidant properties of zinc have long been documented, however, underlying mechanisms are still not entirely clear. Here, we report molecular mechanisms underlying the development of a pro-inflammatory phenotype during zinc deficiency. Furthermore, we describe links between altered zinc homeostasis and disease development. Consequently, the benefits of zinc supplementation for a malfunctioning immune system become clear. This article will focus on underlying mechanisms responsible for the regulation of cellular signaling by alterations in zinc homeostasis. Effects of fast zinc flux, intermediate "zinc waves", and late homeostatic zinc signals will be discriminated. Description of zinc homeostasis-related effects on the activation of key signaling molecules, as well as on epigenetic modifications, are included to emphasize the role of zinc as a gatekeeper of immune function.

Wessels I, Maywald M, Rink L. Zinc as a Gatekeeper of Immune Function. Nutrients. 2017;9(12):1286. Published 2017 Nov 25. doi:10.3390/nu9121286 TITLE: FUTURE PERSPECTIVES IN ADDRESSING THE GLOBAL ISSUE OF VITAMIN D DEFICIENCY

Abstract

Vitamin D is a fundamentally critical nutrient that the human body requires to function properly. It plays an important role in musculoskeletal health due to its involvement in the regulation of calcium and phosphorus. Having a low level of vitamin D in the body may be detrimental for a wide range of health outcomes, including risk of osteoporotic and stress fractures, risk of CVD and some cancers, and lowering of the capability of the immune system. Vitamin D is an unusual nutrient; it is not a vitamin, in the true sense of the word but a pro-hormone. The main source of vitamin D is UV exposure, not dietary intake. Interestingly, there are two forms of vitamin D, vitamin D2 and vitamin D3, both of which are metabolised into 25-hydroxyvitamin D (25(OH)D) in the liver, the biomarker of vitamin D status. Vitamin D deficiency is a global public health problem, especially amongst older people and ethnic minority groups. The newest publication from the UK Government's Public Health England Department recommends that vitamin D intake should be 10 µg daily and this recommendation compares well (albeit lower) with other guidelines such as the Institute of Medicine recommendation of 15 µg for those aged 1-70 years and 20 µg for those 70 years or over. Few countries, however, have a specific vitamin D policy to prevent deficiency in populations. Finland leads the way, demonstrating impressive results in reducing population-level vitamin D deficiency through mandatory food fortification programmes. Collaboration between academia, government and industry, including countries from varying latitudes, is essential to identify long-term solutions to the global issue of vitamin D deficiency. This paper provides a narrative review of the evidence related to the role of vitamin D deficiency in health outcomes, outlines controversies regarding setting levels of adequacy, identifies the prevalence of vitamin D deficiency across the globe, and identifies population-level strategies adopted by countries to prevent vitamin D deficiency.

Mendes MM, Charlton K, Thakur S, Ribeiro H, Lanham-New SA. Future perspectives in addressing the global issue of vitamin D deficiency. Proc Nutr Soc. 2020;79(2):246-251. doi:10.1017/S0029665119001538 PUTATIVE ROLES OF VITAMIN D IN MODULATING IMMUNE RESPONSE AND IMMUNOPATHOLOGY ASSOCIATED WITH COVID-19

Virus Res . 2021 Jan 15

Abstract

The first incidence of COVID-19 was reported in the Wuhan city of Hubei province in China in late December 2019. Because of failure in timely closing of borders of the affected region, COVID-19 spread across like a wildfire through air travel initiating a pandemic. It is a serious lower respiratory track viral infection caused by highly contagious, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Coronavirus including COVID-19 causing SARS-CoV-2 causes zoonotic diseases and thought to be originated from bats. Since its first incidence, the virus has spread all across the world, causing serious human casualties, economic losses, and disrupting global supply chains. As with SARS-CoV, COVID-19 causing SARS-CoV-2 follows a similar path of airborne infection, but is less lethal and more infectious than SARS and MERS. This review focusses on the pathogenesis of SARS-CoV-2, especially on the dysfunctional immune responses following a cytokine storm in severely affected persons. The mode of entry of SARS-CoV-2 is via the angiotensin converting enzyme 2 (ACE-2) receptors present on the epithelial lining of lungs, gastrointestinal tract, and mucus membranes. Older persons with weaker immune system and associated co-morbidities are more vulnerable to have dysfunctional immune responses, as most of them concomitantly have severe hypovitaminosis D. Consequently, causing severe damage to key organs of the body including lungs and the cardiovascular system. Since, vast majority of persons enters to the intensive care units and died, had severe vitamin D deficiency, thus, this area must be investigated seriously. In addition, this article assesses the role of vitamin D in reducing the risk of COVID-19. Vitamin D is a key regulator of the renin-angiotensin system that is exploited by SARS-CoV-2 for entry into the host cells. Further, vitamin D modulates multiple mechanisms of the immune system to contain the virus that includes dampening the entry and replication of SARS-CoV-2, reduces concentration of pro-inflammatory cytokines and increases levels of anti-inflammatory cytokines, enhances the production of natural antimicrobial peptide and activates defensive cells such as macrophages that could destroy SARS-CoV-2. Thus, this article provides the urgency of needed evidences through large population based randomized controlled trials and ecological studies to evaluate the potential role of vitamin D in COVID-19.

Kumar R, Rathi H, Haq A, Wimalawansa SJ, Sharma A. Putative roles of vitamin D in modulating immune response and immunopathology associated with COVID-19. Virus Res. 2021 Jan 15;292:198235. doi: 10.1016/j.virusres.2020.198235. Epub 2020 Nov 21. PMID: 33232783; PMCID: PMC7680047. THREE NOVEL PREVENTION, DIAGNOSTIC, AND TREATMENT OPTIONS FOR COVID-19 URGENTLY NECESSITATING CONTROLLED RANDOMIZED TRIALS

Med Hypotheses . 2020 Oct

Abstract

Purpose: Asymptomatic or minimally symptomatic infection with COVID-19 can result in silent transmission to large numbers of individuals, resulting in expansion of the pandemic with a global increase in morbidity and mortality. New ways of screening the general population for COVID-19 are urgently needed along with novel effective prevention and treatment strategies.

Hypothesis: A hypothetical three-part prevention, diagnostic, and treatment approach based on an up-to-date scientific literature review for COVID-19 is proposed. Regarding diagnosis, a validated screening questionnaire and digital app for COVID-19 could help identify individuals who are at risk of transmitting the disease, as well as those at highest risk for poor clinical outcomes. Global implementation and online tracking of vital signs and scored questionnaires that are statistically validated would help health authorities properly allocate essential health care resources to test and isolate those at highest risk for transmission and poor outcomes. Second, regarding prevention, no validated protocols except for physical distancing, hand washing, and isolation exist, and recently ivermectin has been published to have anti-viral properties against COVID-19. A randomized trial of ivermectin, and/or nutraceuticals that have been published to support immune function including glutathione, vitamin C, zinc, and immunomodulatory supplements (3,6 Beta glucan) could be beneficial in preventing transmission or lessening symptomatology but requires statistical validation. Third, concerning treatment, COVID-19 induced inflammation and "cytokine storm syndrome" with hemophagocytic lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS) have resulted in extreme morbidity and mortality in those with certain comorbidities, secondary to "acute respiratory distress syndrome" (ARDS) and multiorgan dysfunction with disseminated intravascular coagulation (DIC).Deficiency in red blood cell, serum and alveolar glutathione has been published in the medical literature for ARDS, as well as viral and bacterial pneumonias, resulting from increased levels of free radical/oxidative stress. A randomized controlled trial of blocking NF-κB and cytokine formation using glutathione precursors (N-acetyl-cysteine [NAC] and alpha lipoic acid) and PO/IV glutathione with associated anti-viral effects should be performed, along with an evaluation of Nrf2 activators (curcumin, sulforaphane glucosinolate) which have been scientifically proven to lower inflammation. Since high mortality rates from sepsis induced DIC due to COVID-19 infection has also been associated with thrombotic events and elevated levels of D-dimer, randomized controlled trials of using anticoagulant therapy with heparin is urgently required. This is especially important in patients on ventilators who have met certain sepsis induced coagulopathy (SIC) criteria. The use of acetazolamide with or without sildenafil also needs to be explored with or without heparin, since increased oxygen delivery to vital organs through prevention of thrombosis/pulmonary emboli along with carbonic anhydrase inhibition may help increase oxygenation and prevent adverse clinical outcomes.

Conclusion and implications: A three-part prevention, diagnostic, and treatment plan is proposed for addressing the severe complications of COVID-19. Digital monitoring of symptoms to clinically diagnose early exposure and response to treatment; prevention with ivermectin as well as nutritional therapies that support a healthy immune response; treatment with anti-inflammatory therapies that block NF-κB and activate Nrf2 pathways, as well as novel therapies that address COVID-19 pneumonia and ARDS with DIC including anticoagulation and/or novel respiratory therapies with or without acetazolamide and sildenafil. These three broad-based interventions urgently need to be subjected to randomized, controlled trials.

Horowitz RI, Freeman PR. Three novel prevention, diagnostic, and treatment options for COVID-19 urgently necessitating controlled randomized trials. Med Hypotheses. 2020 Oct;143:109851. doi: 10.1016/j.mehy.2020.109851. Epub 2020 May 22. PMID: 32534175; PMCID: PMC7242962. RETEST POSITIVE FOR SARS-COV-2 RNA OF "RECOVERED" PATIENTS WITH COVID-19: PERSISTENCE, SAMPLING ISSUES, OR RE-INFECTION?

J Med Virol . 2020 Nov.

Abstract

"Retest Positive" for severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) from "recovered" coronavirus disease-19 (COVID-19) has been reported and raised several important questions for this novel coronavirus and COVID-19 disease. In this commentary, we discussed several questions: (a) Can SARS-CoV-2 re-infect the individuals who recovered from COVID-19? This question is also associated with other questions: whether or not SARS-CoV-2 infection induces protective reaction or neutralized antibody? Will SARS-CoV-2 vaccines work? (b) Why could some recovered patients with COVID-19 be re-tested positive for SARS-CoV-2 RNA? (c) Are some recovered pwith atients COVID-19 with re-testing positive for SARS-CoV-2 RNA infectious? and (d) How should the COVID-19 patients with retest positive for SARS-CoV-2 be managed?

Kang H, Wang Y, Tong Z, Liu X. Retest positive for SARS-CoV-2 RNA of "recovered" patients with COVID-19: Persistence, sampling issues, or re-infection? J Med Virol. 2020 Nov;92(11):2263-2265. doi: 10.1002/jmv.26114. Epub 2020 Jun 9. PMID: 32492212; PMCID: PMC7300489. A NEW POSITIVE SARS-COV-2 TEST MONTHS AFTER SEVERE COVID-19 ILLNESS: REINFECTION OR INTERMITTENT VIRAL SHEDDING?

BMJ Case Rep . 2021 Feb 4.

Abstract

We present a case of a patient who had a history of severe coronavirus disease (COVID-19) 4 months prior to this current presentation and, after a long asymptomatic period, subsequently tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by a RNA PCR assay, after several interval negative SARS-CoV-2 RNA tests. We present this potential case of SARS- CoV-2 reinfection in order to incite discussion around differentiating persistent infection with intermittent viral shedding and reinfection, as well as to discuss evolving knowledge and approaches to the clinical management, follow-up molecular testing and treatment of COVID-19 reinfection.

Tuan J, Spichler-Moffarah A, Ogbuagu O. A new positive SARS-CoV-2 test months after severe COVID-19 illness: reinfection or intermittent viral shedding? BMJ Case Rep. 2021 Feb 4;14(2):e240531. doi: 10.1136/bcr-2020-240531. PMID: 33542020; PMCID: PMC8098910. CYTOKINE STORM INDUCED BY SARS-COV-2 INFECTION: THE SPECTRUM OF ITS NEUROLOGICAL MANIFESTATIONS

Cytokine . 2021 Feb

Abstract

The new coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can trigger a hyperinflammatory state characterized by elevated cytokine levels known as hypercytokinemia or cytokine storm, observed most often in severe patients. Though COVID-19 is known to be a primarily respiratory disease, neurological complications affecting both the central and peripheral nervous systems have also been reported. This review discusses potential routes of SARS-CoV-2 neuroinvasion and pathogenesis, summarizes reported neurological sequelae of COVID-19, and examines how aberrant cytokine levels may precipitate these complications. Clarification of the pathogenic mechanisms of SARS-CoV-2 is needed to encourage prompt diagnosis and optimized care. In particular, identifying the presence of cytokine storm in patients with neurological COVID-19 manifestations will facilitate avenues for treatment. Future investigations into aberrant cytokine levels in COVID-19 patients with neurological symptoms as well as the efficacy of cytokine storm-targeting treatments will be critical in elucidating the pathogenic mechanisms and effective treatments of COVID-19.

Thepmankorn P, Bach J, Lasfar A, Zhao X, Souayah S, Chong ZZ, Souayah N. Cytokine storm induced by SARS-CoV-2 infection: The spectrum of its neurological manifestations. Cytokine. 2021 Feb;138:155404. doi: 10.1016/j.cyto.2020.155404. Epub 2020 Dec 11. PMID: 33360025; PMCID: PMC7832981. A NETWORK-BASED ANALYSIS REVEALS THE MECHANISM UNDERLYING VITAMIN D IN SUPPRESSING CYTOKINE STORM AND VIRUS IN SARS-COV-2 INFECTION

Front Immunol . 2020 Dec 9

Abstract

Background: SARS-CoV-2 causes ongoing pandemic coronavirus disease of 2019 (COVID-19), infects the cells of the lower respiratory tract that leads to a cytokine storm in a significant number of patients resulting in severe pneumonia, shortness of breathing, respiratory and organ failure. Extensive studies suggested the role of Vitamin D in suppressing cytokine storm in COVID-19 and reducing viral infection; however, the precise molecular mechanism is not clearly known. In this work, bioinformatics and systems biology approaches were used to understand SARS-CoV-2 induced cytokine pathways and the potential mechanism of Vitamin D in suppressing cytokine storm and enhancing antiviral response.

Results: This study used transcriptome data and identified 108 differentially expressed host genes (DEHGs) in SARS-CoV-2 infected normal human bronchial epithelial (NHBE) cells compared to control. Then, the DEHGs was integrated with the human protein-protein interaction data to generate a SARS-CoV-2 induced host gene regulatory network (SiHgrn). Analysis of SiHgrn identified a sub- network "Cluster 1" with the highest MCODE score, 31 up-regulated genes, and predominantly associated immune and inflammatory response. Interestingly, the iRegulone tool identified that "Cluster 1" is under the regulation of transcription factors STAT1, STAT2, STAT3, POU2F2, and NFkB1, collectively referred to as "host response signature network". Functional enrichment analysis with NDEx revealed that the "host response signature network" is predominantly associated with critical pathways, including "cytokines and inflammatory response", "non-genomic action of Vitamin D", "the human immune response to tuberculosis", and "lung fibrosis". Finally, in-depth analysis and literature mining revealed that Vitamin D binds with its receptor and could work through two different pathways: (i) it inhibits the expression of pro-inflammatory cytokines through blocking the TNF induced NFkB1 signaling pathway; and (ii) it initiates the expression of interferon-stimulating genes (ISGs) for antiviral defense program through activating the IFN-α induced Jak-STAT signaling pathway.

Conclusion: This comprehensive study identified the pathways associated with cytokine storm in SARS-CoV-2 infection. The proposed underlying mechanism of Vitamin D could be promising in suppressing the cytokine storm and inducing a robust antiviral response in severe COVID-19 patients. The finding in this study urgently needs further experimental validations for the suitability of Vitamin D in combination with IFN-α to control severe COVID-19.

Ahmed F. A Network-Based Analysis Reveals the Mechanism Underlying Vitamin D in Suppressing Cytokine Storm and Virus in SARS-CoV-2 Infection. Front Immunol. 2020 Dec 9;11:590459. doi: 10.3389/fimmu.2020.590459. PMID: 33362771; PMCID: PMC7756074. DECODING THE SILENT WALK OF COVID-19: HALTING ITS SPREAD USING OLD BULLETS

Biomed Pharmacother . 2021 Jan

Abstract

Severe acute respiratory syndrome (SARS) develops within 3-14 days when CoV2 invades epithelial, myeloid cells in the nasopharynx and pneumocytes in the respiratory tract through angiotensin converting enzyme (ACE2). Infection swiftly disseminates to gastrointestinal, cardiovascular, renal organs as well as immune system to deregulate their normal functioning through unique and distinct mechanisms. The health system and economy has been intensely thwarted by the rapid spread and exorbitant mortality caused by COVID-19 disease across the globe. The acute progression of the disease and high infection rate pose an enormous challenge for its therapeutic management and critical care. The viral structure, genome and proteome have been deciphered which yielded cues for targeting already available therapeutic entities. More than 200 compounds have been screened and till date approximately 69 therapeutic agents are undergoing clinical trials across the world. Among these, remedesivir (RMD), chloroquine (CQ), hydroxychloroquine (HCQ), noscapine (NOS) and heparin have demonstrated fairly promising results in preclinical and clinical studies. Recently, RMD has been approved by USFDA for the management of COVID 19. However, intense research is going on to screen and ace the 'magic bullets' for the management of SARS-CoV2 infection worldwide. The current review illustrates the plausible therapeutic targets in SARS-CoV2 important for inhibition of virus cycle. In addition, the role of RMD, CQ, HCQ, NOS and heparin in combating infection has been addressed. The importance of vitamin C and D supplements as adjunct therapies in the prevention of SARS-CoV2 virus infection have also been summarized.

Kumar M, Madan J, Sodhi RK, Singh SB, Katyal A. Decoding the silent walk of COVID-19: Halting its spread using old bullets. Biomed Pharmacother. 2021 Jan;133:110891. doi: 10.1016/j.biopha.2020.110891. Epub 2020 Oct 19. PMID: 33227700; PMCID: PMC7572089.

NUTRITION

EVIDENCE BASED DIET RELATED RESEARCH Intermittent Fasting Ketogenic Diet Plant Based Nutrition NUTRITION DISCLAIMER-

Just Remember, Nutrition Is One Of The Hardest Topics To Cover As Guidelines Are Always Changing & Diets Are Open To Different Interpretation. Intermittent Fasting

Complete Involves alternating fasting days (no energy-containing foods or Alternate beverages consumed) with eating days (food and beverages Day Fasting consumed ad libitum) Time No eating anything but water after dinner. No snacking in the Restricted evening. Eating can be resumed the following day any time Feeding before noon. Eating is permitted until after dinner. Religious Variety of fasting regimens undertaken for religious or spiritual Fasting purposes, ie. Yom Kippur (Judaism) 25.5hr fast - no food or water. Ramadan A fast from sunrise to sunset during the holy month of Ramada; Fasting the most common dietary practice is to consume one large meal after sunset and one lighter meal before dawn. Thus, the feast and fast periods of Ramadan are approximately 12 hours in length Other Members of the Church of Jesus Christ of Latter-Day Saints Religious routinely abstain from food and drink for extended periods of Fasts time. Some Seventh-day Adventists consume their last of two https://academic.oup.com/nutritionreviews/article/73/10/661/1849182daily meals in the afternoon, resulting in an extended nighttime fasting interval that may be biologically important TITLE: EFFECTS OF INTERMITTENT FASTING ON BODY COMPOSITION AND CLINICAL HEALTH MARKERS IN HUMANS

Intermittent fasting is a broad term that encompasses a variety of programs that manipulate the timing of eating occasions by utilizing short-term fasts in order to improve body composition and overall health. This review examines studies conducted on intermittent fasting programs to determine if they are effective at improving body composition and clinical health markers associated with disease. Intermittent fasting protocols can be grouped into alternate-day fasting, whole-day fasting, and time- restricted feeding. Alternate-day fasting trials of 3 to 12 weeks in duration appear to be effective at reducing body weight (≈3%-7%), body fat (≈3-5.5 kg), total cholesterol (≈10%-21%), and triglycerides (≈14%-42%) in normal-weight, overweight, and obese humans. Whole-day fasting trials lasting 12 to 24 weeks also reduce body weight (≈3%-9%) and body fat, and favorably improve blood lipids (≈5%-20% reduction in total cholesterol and ≈17%-50% reduction in triglycerides). Research on time-restricted feeding is limited, and clear conclusions cannot be made at present. Future studies should examine long-term effects of intermittent fasting and the potential synergistic effects of combining intermittent fasting with exercise.

Tinsley GM, La Bounty PM. Effects of intermittent fasting on body composition and clinical health markers in humans. Nutr Rev. 2015;73(10):661-674. doi:10.1093/nutrit/nuv041 TITLE: METABOLIC EFFECTS OF INTERMITTENT FASTING

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved health outcomes. A MEDLINE search was performed using PubMed and the terms "intermittent fasting," "fasting," "time-restricted feeding," and "food timing." Modified fasting regimens appear to promote weight loss and may improve metabolic health. Several lines of evidence also support the hypothesis that eating patterns that reduce or eliminate nighttime eating and prolong nightly fasting intervals may result in sustained improvements in human health. Intermittent fasting regimens are hypothesized to influence metabolic regulation via effects on (a) circadian biology, (b) the gut microbiome, and (c) modifiable lifestyle behaviors, such as sleep. If proven to be efficacious, these eating regimens offer promising nonpharmacological approaches to improving health at the population level, with multiple public health benefits.

Patterson RE, Sears DD. Metabolic Effects of Intermittent Fasting. Annu Rev Nutr. 2017;37:371-393. doi:10.1146/ annurev-nutr-071816-064634 TITLE: IMPACT OF INTERMITTENT FASTING ON THE LIPID PROFILE: ASSESSMENT ASSOCIATED WITH DIET AND WEIGHT LOSS

Intermittent fasting, whose proposed benefits include the improvement of lipid profile and the body weight loss, has gained considerable scientific and popular repercussion. This review aimed to consolidate studies that analyzed the lipid profile in humans before and after intermittent fasting period through a detailed review; and to propose the physiological mechanism, considering the diet and the body weight loss. Normocaloric and hypocaloric intermittent fasting may be a dietary method to aid in the improvement of the lipid profile in healthy, obese and dyslipidemic men and women by reducing total cholesterol, LDL, triglycerides and increasing HDL levels. However, the majority of studies that analyze the intermittent fasting impacts on the lipid profile and body weight loss are observational based on Ramadan fasting, which lacks large sample and detailed information about diet. Randomized clinical trials with a larger sample size are needed to evaluate the IF effects mainly in patients with dyslipidemia.

Santos HO, Macedo RCO. Impact of intermittent fasting on the lipid profile: Assessment associated with diet and weight loss. Clin Nutr ESPEN. 2018;24:14-21. doi:10.1016/j.clnesp.2018.01.002 TITLE: FASTING FOR WEIGHT LOSS: AN EFFECTIVE STRATEGY OR LATEST DIETING TREND?

With the increasing obesity epidemic comes the search for effective dietary approaches for calorie restriction and weight loss. Here I examine whether fasting is the latest 'fad diet' as portrayed in popular media and discuss whether it is a safe and effective approach or whether it is an idiosyncratic diet trend that promotes short-term weight loss, with no concern for long-term weight maintenance. Fasting has long been used under historical and experimental conditions and has recently been popularised by 'intermittent fasting' or 'modified fasting' regimes, in which a very low-calorie allowance is allowed, on alternate days (ADF) or 2 days a week (5:2 diet), where 'normal' eating is resumed on non-diet days. It is a simple concept, which makes it easy to follow with no difficult calorie counting every other day. This approach does seem to promote weight loss, but is linked to hunger, which can be a limiting factor for maintaining food restriction. The potential health benefits of fasting can be related to both the acute food restriction and chronic influence of weight loss; the long- term effect of chronic food restriction in humans is not yet clear, but may be a potentially interesting future dietary strategy for longevity, particularly given the overweight epidemic. One approach does not fit all in the quest to achieve body weight control, but this could be a dietary strategy for consideration. With the obesity epidemic comes the search for dietary strategies to (i) prevent weight gain, (ii) promote weight loss and (iii) prevent weight regain. With over half of the population of the United Kingdom and other developed countries being collectively overweight or obese, there is considerable pressure to achieve these goals, from both a public health and a clinical perspective. Certainly not one dietary approach will solve these complex problems. Although there is some long-term success with gastric surgical options for morbid obesity, there is still a requirement for dietary approaches for weight management for the overweight and obese population, particularly as invasive interventions carry post-operative risk of death due to complications. Effective dietary interventions are required that promote long-term adherence and sustained beneficial effects on metabolic and disease markers. In general, such interventions need to be palatable and satiating, meet minimal nutritional requirements, promote loss of fat and preserve lean body mass, ensure long-term safety, be simple to administer and monitor and have widespread public health utility. Intermittent fasting or alternate day fasting may be an option for achieving weight loss and maintenance.

Johnstone A. Fasting for weight loss: an effective strategy or latest dieting trend?. Int J Obes (Lond). 2015;39(5):727-733. doi:10.1038/ijo.2014.214 KETOGENIC DIET

!A diet moderate in proteins (lean meats, fish) and high fats, low in carbohydrates. i.e. healthy fats avocado, nuts, and olive oil. !In absence of circulating blood sugar from food, we start breaking down stored fat into ketone bodies to generate energy. !Difficult to sustain over a long period of time. TITLE: HISTORY OF THE KETOGENIC DIET

Abstract

Fasting and other dietary regimens have been used to treat epilepsy since at least 500 BC. To mimic the metabolism of fasting, the ketogenic diet (KD) was introduced by modern physicians as a treatment for epilepsy in the 1920s. For two decades this therapy was widely used, but with the modern era of antiepileptic drug treatment its use declined dramatically. By the end of the twentieth century this therapy was available in only a small number of children's hospitals. Over the past 15 years, there has been an explosion in the use, and scientific interest in the KD. This review traces the history of one of the most effective treatments for childhood epilepsy.

Wheless JW. History of the ketogenic diet. Epilepsia. 2008;49 Suppl 8:3-5. doi:10.1111/j.1528-1167.2008.01821.x TITLE: INFLUENCE OF THE MEDITERRANEAN AND KETOGENIC DIETS ON COGNITIVE STATUS AND DECLINE: A NARRATIVE REVIEW

Abstract

Alzheimer's disease (AD) is the most common form of senile dementia, accounting for up to 70% of dementia cases. AD is a slowly progressive disease, which causes global mental deterioration by affecting various cognitive areas. A growing body of evidence has demonstrated that lifestyle habits and nutritional patterns could delay the natural course of the neurodegeneration process. There is no single dietary pattern unequivocally proven to prevent AD. Nevertheless, epidemiological data suggest that by adopting several dietary habits, especially if accompanied with a healthy lifestyle, the negative consequences of AD could potentially be delayed. Alongside with others, two specific eating patterns have been well investigated concerning their potential beneficial effect on cognitive status: the Mediterranean diet (MedDi) and the Ketogenic Diet (KD). Despite the different underlying mechanisms, both of them have demonstrated a fairly profitable role in reducing or delaying cognitive impairment. The aim of the present narrative review is to overview the existing research on the efficacy of MedDi and KD against AD-related cognitive decline, focusing on the proposed protective mechanisms of action. Although the current knowledge on this complex topic does not allow us, at this point, to make exhaustive conclusions, this information could be of help in order to better characterize the possible role of MedDi and KD as nonpharmacological therapies in the treatment of AD and, more generically, of neurodegenerative disorders.

Vinciguerra F, Graziano M, Hagnäs M, Frittitta L, Tumminia A. Influence of the Mediterranean and Ketogenic Diets on Cognitive Status and Decline: A Narrative Review. Nutrients. 2020;12(4):1019. Published 2020 Apr 8. doi:10.3390/nu12041019 TITLE: THE KETOGENIC DIET AND SPORT: A POSSIBLE MARRIAGE?

Abstract

The ketogenic diet (KD) is used widely as a weight loss strategy and, more rarely, as therapy for some diseases. In many sports, weight control is often necessary (boxing, weightlifting, wrestling, etc.), but the KD usually is not considered. Our hypothesis is that KD might be used to achieve fat loss without affecting strength/power performance negatively.

Paoli A, Bianco A, Grimaldi KA. The Ketogenic Diet and Sport: A Possible Marriage?. Exerc Sport Sci Rev. 2015;43(3):153-162. doi:10.1249/JES.0000000000000050 TITLE: KETOGENIC DIET IN ALZHEIMER'S DISEASE

Abstract

At present, the prevalence of Alzheimer's disease, a devastating neurodegenerative disorder, is increasing. Although the mechanism of the underlying pathology is not fully uncovered, in the last years, there has been significant progress in its understanding. This includes: Progressive deposition of amyloid β-peptides in amyloid plaques and hyperphosphorylated tau protein in intracellular as neurofibrillary tangles; neuronal loss; and impaired glucose metabolism. Due to a lack of effective prevention and treatment strategy, emerging evidence suggests that dietary and metabolic interventions could potentially target these issues. The ketogenic diet is a very high-fat, low-carbohydrate diet, which has a fasting-like effect bringing the body into a state of ketosis. The presence of ketone bodies has a neuroprotective impact on aging brain cells. Moreover, their production may enhance mitochondrial function, reduce the expression of inflammatory and apoptotic mediators. Thus, it has gained interest as a potential therapy for neurodegenerative disorders like Alzheimer's disease. This review aims to examine the role of the ketogenic diet in Alzheimer's disease progression and to outline specific aspects of the nutritional profile providing a rationale for the implementation of dietary interventions as a therapeutic strategy for Alzheimer's disease.

Rusek M, Pluta R, Ułamek-Kozioł M, Czuczwar SJ. Ketogenic Diet in Alzheimer's Disease. Int J Mol Sci. 2019;20(16):3892. Published 2019 Aug 9. doi:10.3390/ijms20163892 TITLE: KETOGENIC DIET AS A METABOLIC THERAPY FOR MOOD DISORDERS: EVIDENCE AND DEVELOPMENTS

Abstract

Despite significant advances in pharmacological and non-pharmacological treatments, mood disorders remain a significant source of mental capital loss, with high rates of treatment resistance, requiring a coordinated effort in investigation and development of efficient, tolerable and accessible novel interventions. Ketogenic diet (KD) is a low-carb diet that substantially changes the energetic matrix of the body including the brain. It has been established as an effective anticonvulsant treatment, and more recently, the role of KD for mental disorders has been explored. Ketogenic diet has profound effects in multiple targets implicated in the pathophysiology of mood disorders, including but not limited to, glutamate/GABA transmission, monoamine levels, mitochondrial function and biogenesis, neurotrophism, oxidative stress, insulin dysfunction and inflammation. Preclinical studies, case reports and case series have demonstrated antidepressant and mood stabilizing effects of KD, however, to date, no clinical trials for depression or bipolar disorder have been conducted. Because of its potential pleiotropic benefits, KD should be considered as a promising intervention in research in mood disorder therapeutics, especially in treatment resistant presentations.

Brietzke E, Mansur RB, Subramaniapillai M, et al. Ketogenic diet as a metabolic therapy for mood disorders: Evidence and developments. Neurosci Biobehav Rev. 2018;94:11-16. doi:10.1016/j.neubiorev.2018.07.020 PLANT BASED DIET

!Focuses on vegetables, fruits, grains (especially whole grains), beans and peas, lentils, nuts, and seeds (rather than on meat, poultry, fish, eggs, and dairy foods). It is not necessarily meatless or vegan. (Plant based burgers.)

!Min. 70% of every plate ate is plant based. TITLE: A PLANT-BASED DIET, ATHEROGENESIS, AND CORONARY ARTERY DISEASE PREVENTION

Abstract

A plant-based diet is increasingly becoming recognized as a healthier alternative to a diet laden with meat. Atherosclerosis associated with high dietary intake of meat, fat, and carbohydrates remains the leading cause of mortality in the US. This condition results from progressive damage to the endothelial cells lining the vascular system, including the heart, leading to endothelial dysfunction. In addition to genetic factors associated with endothelial dysfunction, many dietary and other lifestyle factors, such as tobacco use, high meat and fat intake, and oxidative stress, are implicated in atherogenesis. Polyphenols derived from dietary plant intake have protective effects on vascular endothelial cells, possibly as antioxidants that prevent the oxidation of low-density lipoprotein. Recently, metabolites of L-carnitine, such as trimethylamine-N-oxide, that result from ingestion of red meat have been identified as a potential predictive marker of coronary artery disease (CAD). Metabolism of L- carnitine by the intestinal microbiome is associated with atherosclerosis in omnivores but not in vegetarians, supporting CAD benefits of a plant-based diet. Trimethylamine-N-oxide may cause atherosclerosis via macrophage activation. We suggest that a shift toward a plant-based diet may confer protective effects against atherosclerotic CAD by increasing endothelial protective factors in the circulation while reducing factors that are injurious to endothelial cells. The relative ratio of protective factors to injurious endothelial exposure may be a novel approach to assessing an objective dietary benefit from a plant-based diet. This review provides a mechanistic perspective of the evidence for protection by a plant-based diet against atherosclerotic CAD.

Tuso P, Stoll SR, Li WW. A plant-based diet, atherogenesis, and coronary artery disease prevention. Perm J. 2015;19(1):62-67. doi:10.7812/TPP/14-036 TITLE: PLANT-BASED DIETS: CONSIDERATIONS FOR ENVIRONMENTAL IMPACT, PROTEIN QUALITY, AND EXERCISE PERFORMANCE Abstract

Plant-based diets provide well-established physical and environmental health benefits. These benefits stem in part from the degree of restriction of animal-derived foods. Historically, meat and other animal-derived proteins have been viewed as an integral component of athletes' diets, leading some to question the adequacy of vegetarian or vegan diets for supporting athletic performance. The purpose of this review is to examine the impact of plant-based diets on human physical health, environmental sustainability, and exercise performance capacity. Based on currently available literature, it is unlikely that plant-based diets provide advantages, but do not suffer from disadvantages, compared to omnivorous diets for strength, anaerobic, or aerobic exercise performance. However, plant- based diets typically reduce the risk of developing numerous chronic diseases over the lifespan and require fewer natural resources for production compared to meat-containing diets. As such, plant-based diets appear to be viable options for adequately supporting athletic performance while concurrently contributing to overall physical and environmental health. Given the sparse literature comparing omnivore, vegetarian, and vegan athletes, particularly at the elite level, further research is warranted to ascertain differences that might appear at the highest levels of training and athletic performance.

Lynch H, Johnston C, Wharton C. Plant-Based Diets: Considerations for Environmental Impact, Protein Quality, and Exercise Performance. Nutrients. 2018;10(12):1841. Published 2018 Dec 1. doi:10.3390/nu10121841 TITLE: CARDIO-METABOLIC BENEFITS OF PLANT-BASED DIETS

Abstract

Cardio-metabolic disease, namely ischemic heart disease, stroke, obesity, and type 2 diabetes, represent substantial health and economic burdens. Almost one half of cardio-metabolic deaths in the U.S. might be prevented through proper nutrition. Plant-based (vegetarian and vegan) diets are an effective strategy for improving nutrient intake. At the same time, they are associated with decreased all-cause mortality and decreased risk of obesity, type 2 diabetes, and coronary heart disease. Evidence suggests that plant-based diets may reduce the risk of coronary heart disease events by an estimated 40% and the risk of cerebral vascular disease events by 29%. These diets also reduce the risk of developing metabolic syndrome and type 2 diabetes by about one half. Properly planned vegetarian diets are healthful, effective for weight and glycemic control, and provide metabolic and cardiovascular benefits, including reversing atherosclerosis and decreasing blood lipids and blood pressure. The use of plant-based diets as a means of prevention and treatment of cardio-metabolic disease should be promoted through dietary guidelines and recommendations.

Kahleova H, Levin S, Barnard N. Cardio-Metabolic Benefits of Plant-Based Diets. Nutrients. 2017;9(8):848. Published 2017 Aug 9. doi:10.3390/nu9080848 TITLE: ASSOCIATION BETWEEN RED MEAT CONSUMPTION AND COLON CANCER: A SYSTEMATIC REVIEW OF EXPERIMENTAL RESULTS

Abstract A role for red and processed meat in the development of colorectal cancer has been proposed based largely on evidence from observational studies in humans, especially in those populations consuming a westernized diet. Determination of causation specifically by red or processed meat is contingent upon identification of plausible mechanisms that lead to colorectal cancer. We conducted a systematic review of the available evidence to determine the availability of plausible mechanistic data linking red and processed meat consumption to colorectal cancer risk. Forty studies using animal models or cell cultures met specified inclusion criteria, most of which were designed to examine the role of heme iron or heterocyclic amines in relation to colon carcinogenesis. Most studies used levels of meat or meat components well in excess of those found in human diets. Although many of the experiments used semi-purified diets designed to mimic the nutrient loads in current westernized diets, most did not include potential biologically active protective compounds present in whole foods. Because of these limitations in the existing literature, there is currently insufficient evidence to confirm a mechanistic link between the intake of red meat as part of a healthy dietary pattern and colorectal cancer risk. Impact statement Current recommendations to reduce colon cancer include the reduction or elimination of red or processed meats. These recommendations are based on data from epidemiological studies conducted among cultures where meat consumption is elevated and consumption of fruits, vegetables, and whole grains are reduced. This review evaluated experimental data exploring the putative mechanisms whereby red or processed meats may contribute to colon cancer. Most studies used levels of meat or meat-derived compounds that were in excess of those in human diets, even in cultures where meat intake is elevated. Experiments where protective dietary compounds were used to mitigate the extreme levels of meat and meat-derived compounds showed protection against colon cancer, with some essentially negating the impact of meat in the diet. It is essential that better-designed studies be conducted that use relevant concentrations of meat or meat-derived compounds in complex diets representative of the foods consumed by humans.

Turner ND, Lloyd SK. Association between red meat consumption and colon cancer: A systematic review of experimental results. Exp Biol Med (Maywood). 2017;242(8):813-839. doi:10.1177/1535370217693117 TITLE: RED AND PROCESSED MEATS AND HEALTH RISKS: HOW STRONG IS THE EVIDENCE?

Abstract

Prevailing dietary guidelines have widely recommended diets relatively low in red and processed meats and high in minimally processed plant foods for the prevention of chronic diseases. However, an ad hoc research group called the Nutritional Recommendations (NutriRECS) consortium recently issued "new dietary guidelines" encouraging individuals to continue their current meat consumption habits due to "low certainty" of the evidence, difficulty of altering meat eaters' habits and preferences, and the lack of need to consider environmental impacts of red meat consumption. These recommendations are not justified, in large part because of the flawed methodologies used to review and grade nutritional evidence. The evidence evaluation was largely based on the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria, which are primarily designed to grade the strength of evidence for clinical interventions especially pharmacotherapy. However, the infeasibility for conducting large, long-term randomized clinical trials on most dietary, lifestyle, and environmental exposures makes the criteria inappropriate in these areas. A separate research group proposed a modified and validated system for rating the meta-evidence on nutritional studies (NutriGRADE) to address several limitations of the GRADE criteria. Applying NutriGRADE, the evidence on the positive association between red and processed meats and type 2 diabetes was rated to be of "high quality," while the evidence on the association between red and processed meats and mortality was rated to be of "moderate quality." Another important limitation is that inadequate attention was paid to what might be replacing red meat, be it plant-based proteins, refined carbohydrates, or other foods. In summary, the red/processed meat recommendations by NutriRECS suffer from important methodological limitations and involve misinterpretations of nutritional evidence. To improve human and planetary health, dietary guidelines should continue to emphasize dietary patterns low in red and processed meats and high in minimally processed plant foods such as fruits and vegetables, whole grains, nuts, and legumes.

Qian F, Riddle MC, Wylie-Rosett J, Hu FB. Red and Processed Meats and Health Risks: How Strong Is the Evidence?. Diabetes Care. 2020;43(2):265-271. doi:10.2337/dci19-0063 Chiropractic Adjustive Technique

I. ADVANCED CHIROPRACTIC ADJUSTIVE TECHNIQUE I. Overview of Clinical Posture Neurology II. POSTURE ANALYSIS / EVALUATION OF A TO P AND LATERAL POSTURES I. Functional Movement Techniques using kinesio-tape for posture correction. II. POSTURE CORRECTION/ INSTRUMENT PROPRIOCEPTIVE POSTURE BALANCING III. POSTURE & SYSTEMIC HEALTH- A REVIEW OF THE MEDICAL LITERATURE IV. FORWARD HEAD POSTURE RESEARCH IN CHILDREN V. A CURRENT REVIEW OF NEUROLOGY LITERATURE INCLUDING: POSTURE, PROPRIOCEPTION & POSTURE, AND CONDITIONS COMMONLY TREATED BY CHIROPRACTIC METHODS. VI. INTRODUCTION TO DIVERSIFIED MYOFACIAL RELEASE PROCEDURES VII. INSTRUMENT ASSISTED MUSCLE BALANCING VIII. FIBROTIC ADHESIONS, MYOSPASMS AND PIRIFORMIS WORK WITH INSTRUMENT’S IN COMPETITIVE ATHLETES Cerebellum & Posture

• The cerebellum increased in size in the course of vertebrate evolution. The large size in the human brain coincides with the need for synergy of muscles, especially for the maintenance of the erect posture. - The Human Nervous System: An Anatomical viewpoint. Murray Barr and John Kieman

• The cerebellum is responsible for the regulation and control of muscular tone, the coordination of movement, and the control of posture and gait. - Principles of Neurology. Raymond Adams, Maurice Victor, Allan Roper, McGraw-Hill 1997

• The cerebellar input originates in proprioceptors and exterocepetors and is conveyed by massive afferent channels like the spinocerebellar, cuneocerebellar and vestibulocerebellar tracts. This input provides raw data about the condition and interrelationships of parts of the skeletomuscular system and of the body as a whole. PHYSIOLOGICAL EFFECTS OF TAPING ON THE HUMAN BODY

! Purpose of Taping:

1. Pain Mitigation

2. Decompression

3. Neurosensory Input ! Two effects of taping:

1. Tape mechanically decompresses the skin and underlying tissues

2. Stimulates sensory nerves in the skin. TAPING ! As tape lifts it alters the afferent signals going from the taped area to the brain.

! This changes the brain’s response to the incoming information, altering the efferent signals returning to the taped area.

! Tape alters proprioception, muscle contraction, range of motion. TAPING CAUTIONS & CONTRAINDICATIONS

• Cautions: • Sensitive Skin & Skin allergies • Infants, elderly, and over a pregnancy • Don’t crank tape. Doesn’t work longer than 5 minutes. • DON’T RIP OFF • Contraindications • Open wounds, skin infection, cancer, deep vein thrombosis, kidney disease, and congestive heart failure, systemic edema. TAPE CARE

• Patient’s skin must be clean and dry.

• Use rubbing alcohol mixed with 80% water.

• If hair is impeding adherence of tape application, hair should

be shaved or trimmed by patient only.

• Round all edges of tape. This will help it not peel. Rub tap to

activate adhesive

• Tape can last up to 5 days (NO LONGER) and is water resistant.

• If tape gets wet, DO NOT use hair dryers. Pat dry with a towel.

• To take off DO NOT rip off. Gently take off in hot shower or with baby oil or lathery soap. POSTURE TAPING METHOD

• Make sure to put the patient in the opposite/neutral postural pattern and then tape!

• Posture taping requires 1-3 pieces of tape.

• 2 Stabilizing Pieces - These are ran along the length of the area being taped.

• Applied with NO stretch, apply with anchors on both top and bottom

• 1 Decompression Piece( Mostly used if patient is having pain) - Applied perpendicular (90°) to the stabilization strip

• No anchors tear in middle of tape

• Applied with 0-50% of stretch in the middle and are applied over area of greatest pain

• Make sure all tape endings are on skin NOT tape. FUNCTIONAL MOVEMENT TAPING RESEARCH EFFECTS OF KINESIO TAPING AND EXERCISE ON FORWARD HEAD POSTURE.

BACKGROUND: Little is known about the effects of Kinesio taping and therapeutic exercise on correcting forward head posture.

OBJECTIVE:To compare Kinesio taping versus therapeutic exercise for forward head posture on static posture, dynamic mobility and functional outcomes.

METHODS:Siixty subjects (31 women, 29 men) with forward head postures participated in this study. They were randomly assigned to either one of the three groups: (1) exercise group (n = 20), (2) taping group (n = 20), and (3) control groups (n = 20). The horizontal forward displacement (HFD) between ear lobe and acromion process, upper cervical and lower cervical angle (UCA, LCA), active range of motion (AROM) of cervical spine, and neck disability index (NDI) were measured before and after a 5-week intervention, and a 2-week follow-up. Data were analyzed by means of a mixed design repeated-measures ANOVA.

RESULTS: Both taping and exercise groups showed significant improvements in HFD compared with the control group at post-treatment and follow-up. Compared with the control group, the exercise group exhibited significant improvements in the LCA and the side bending AROM at post-treatment. CONCLUSIONS: Both Kinesio taping and therapeutic exercise improve forward head posture after intervention and a 2-week follow-up. The effectiveness of therapeutic exercise is better than taping.

J Back Musculoskelet Rehabil. 2017;30(4):725-733. doi: 10.3233/BMR-150346. ECCENTRIC EXERCISE, KINESIOLOGY TAPE, AND BALANCE IN HEALTHY MEN

OBJECTIVE: To investigate the influence of KT at KT of influence investigate the OBJECTIVE:To Participants performed INTERVENTION(S): the ability The to MEASURE(S): OUTCOME MAIN ina resulted exercise Eccentric RESULTS: KT joint, knee the Applied to CONCLUSIONS: the knee joint on balance ability on joint men inhealthy knee the exercise. eccentric after joint knee the at KT balancewithandwithout test on 2 separate days. maintainbalance was assessed a during usingacomputerized single-legged-stance test balance-stabilitywas test system. The test performed30 of minutes andafter before downhillatreadmill. walking on balance ability,of whichwas deterioration analyses Further KT. of use by the attenuated effectiveness the that depended KT of revealed participant's balance the status,with on effect being preventive withpoorer inparticipants presenting greater baselinebalance ability. deterioration exercise-related the counteracted balancewas tape ability of no when observed Participantsused. balancewithbelow-average ability presenting KT. from benefit more received impairment exercise-related Bypreventing of balancehelpto ability, might KT injuries. sport-associated riskknee of the reduce ! ! ! ! !

J Athl Train. 2017 Jul;52(7):636-642. doi: 10.4085/1062-6050-52.3.11. Epub 2017 Apr 18. CERVICOTHORACIC FMT POSTURAL CONTROL TAPING

! Forward head posture, slumped and rounded shoulders, and/or unleveling of the shoulders. ! 1. Position patient in the opposite (neutral), but NOT exaggerated, of their unwanted posture. ! 2. Simply position the patient where you want them and apply the tape. TAPING CODES

Typical allowance for each code is $60.00 to $80.00

29200 Thorax 29520 Hip 29240 Shoulder 29530 Knee 29260 Elbow/wrist 29540 Ankle/ Foot 29280 Hand/ finger 29550 Toes POSTURE BALANCING

Patient standing in front of a mirror with eyes closed. 1) Head in extension then flexion, then back to where they think its center. Hold for 5 seconds. 1. Head/ Neck Lateral Translation or Deviation Main listing usually has symptoms associated with this listing. 2. Head Tilt Right/Left (most common listing you will see) 3. Head Rotation: Right/left (may have symptoms) 4. High Shoulder right/left ( lowest of priority list 1) Lateral Hip Translation

(The deviation is toward the high hip side. Pants pocket may appear higher)

2) Forward Hip Rotation (Pocket is rotating forward)

3) Lateral Posture A) Forward Head Posture of the shoulders

and body

B) Rounded forward shoulders

C)Dowager hump- T1/ T2 area

D) Hyperlordosis Posture Correction

1. Mirror image setup, (opposite posture that the patient presented.)

2. Super stress posture into the opposite pattern (stress posture into passive range of motion.)

3. Stimulate areas of large proprioceptive beds with a high speed, low force instrument or hand.(Lower forces are preferred.) Ex.) In the upper torso regions, stimulate lightly on skin, anywhere in upper cervical area. Ex.) For lower torso regions, stimulate iliac crest or SI Joints Posture Correction

4. Stimulate other proprioceptive areas to reinforce cerebellar learning. Ex) Shoulder paraspinals, rhomboids, achillies tendon. 5. Adjust posture in standing position if possible or lying down or sitting. 6. Deviations/Translations Cervical/Lumbar Lying down with posture blocks (preferred set up). 7. Always balance posture last. MIRROR IMAGING

Is when you put the patient into the opposite postural pattern, than what the patient originally presented to you with when they came in. This process is called Mirror Imaging. It is also the set up for your posture correction.

Before Right head tilt

Before Right high Shoulder Place patient in the opposite postural pattern they presented with.

Right shoulder down Tilt head to the left After postural balancing.

After Shoulders level After Head Level MYOFASCIAL RELEASE - DONE BY HAND ONLY

• A manual therapy that focuses on pain/tightness from the myofascial tissues . • During therapy, find the myofasical area that feels stiff and fixed instead of elastic and movable under light manual pressure. • Manually apply pressure and stretching will help loosen up restricted movement, leading to reduced pain.

http://www.mayoclinic.org/diseases-conditions/back-pain/expert-answers/myofascial- release/faq-20058136 EFFECT OF EXAMS PERIOD ON PREVALENCE OF MYOFASCIAL TRIGGER POINTS AND HEAD POSTURE IN UNDERGRADUATE STUDENTS: REPEATED MEASUREMENTS STUDY.

BACKGROUND: Myofascial Trigger points (MTrPs) may be caused or aggravated by many factors, such as mental stress associated with exams and impaired posture.

METHODS: 39 physical therapy students were palpated for MTrPs in neck and shoulder muscles and were photographed laterally for FHP measurement during the academic semester and during the academic examination period.

RESULTS: The subjects showed higher prevalence of active MTrPs in the right Trapezius and Levator Scapula muscles, and higher prevalence of latent MTrPs in the left Sternocleidomastoideus and Levator Scapula muscles during exams, as well as a higher rate of tenderness in suboccipital musculature.

CONCLUSIONS: Physical therapy students show greater prevalence of MTrPs during exams. The authors recommend implementing preventative programs towards the examination period.

J Bodyw Mov Ther. 2017 Jan;21(1):11-18. doi: 10.1016/j.jbmt.2016.04.003. PREDICTORS OF UPPER TRAPEZIUS PAIN WITH MYOFASCIAL TRIGGER POINTS IN FOOD SERVICE WORKERS: THE STROBE STUDY.

! Shoulder pain occurs commonly in food service workers (FSWs) who repetitively perform motions of the upper limbs. Myofascial trigger points (MTrPs) on the upper trapezius (UT) are among the most common musculoskeletal shoulder pain syndromes. This study determined the psychological, posture, mobility, and strength factors associated with pain severity in FSWs with UT pain due to MTrPs. In this cross-sectional study, we measured 17 variables in 163 FSWs with UT pain due to MTrPs: a visual analog scale (VAS) pain score, age, sex, Borg rating of perceived exertion (BRPE) scale, beck depression inventory, forward head posture angle, rounded shoulder angle (RSA), shoulder slope angle, scapular downward rotation ratio, cervical lateral-bending side difference angle, cervical rotation side difference angle, glenohumeral internal rotation angle, shoulder horizontal adduction angle, serratus anterior (SA) strength, lower trapezius (LT) strength, bicep strength, and glenohumeral external rotator strength, in 163 FSWs with UT pain due to MTrPs. The model for factors influencing UT pain with MTrPs included SA strength, age, BRPE, LT strength, and RSA as predictor variables that accounted for 68.7% of the variance in VAS (P < .001) in multiple regression models with a stepwise selection procedure. The following were independent variables influencing the VAS in the order of standardized coefficients: SA strength (β = -0.380), age (β = 0.287), BRPE (β = 0.239), LT strength (β = -0.195), and RSA (β = 0.125).SA strength, age, BRPE, LT strength, and RSA variables should be considered when evaluating and intervening in UT pain with MTrPs in FSWs.

Medicine (Baltimore). 2017 Jun;96(26):e7252. doi: 10.1097/MD.0000000000007252. ELECTRICAL MASSAGERS

Massage is a great adjunctive therapy to use for preparatory readiness of muscle tissues.

1. Only use on large muscle groups, NEVER over bony process or in the cervical spine. Not near hair or on bare skin. (Only over material or towel.)

2. T1- L5 in the paraspinal muscle region, gluteus region and around shoulder musculature region.

3. May go slightly deeper on extremely muscular athletes. - 4 seconds on one spot, then move location.

4. Treatment lasts between 1 and 2 minutes unless spasm releases earlier

5. Go Light & be careful. PIRIFORMIS SYNDROME

The piriformis muscle irritates the sciatic nerve, causing pain in the buttocks, and referring pain along the entire course of the sciatic nerve.

! Deep buttock pain which is made worse by sitting, stairs, or squats.

! Piriformis muscle lies deep to the gluteal muscles. It originates from the sacral spine and attaches to the greater trochanter. The sciatic nerve usually passes underneath the piriformis muscle, but in 15% of the population it travels through the muscle.

! Treatment will include progressive piriformis stretching starting with four seconds of sustained stretch with an electric massager, elbow or thumb, for up to 60sec. sustained stretch using your hands. A CRITICAL OVERVIEW OF THE CURRENT MYOFASCIAL PAIN LITERATURE - OCTOBER 2017

J Bodyw Mov Ther . 2017 Oct.

Abstract

In this overview of the myofascial pain literature, we have included several original contributions ranging from a study by Bowen and colleagues of trigger points in horses to the introduction of a new clinical entity of "laryngeal muscle myofascial pain syndrome in dysphonic patients." Minerbi and colleagues described for the first time the referred pain patterns of the longus colli muscle, while Casale and associates studied the spinal modulatory action of dry needling or acupuncture stimulation. Many dry needling articles are included in this overview with several recent outcome studies. Slowly, there is increasing scientific support for using dry needling for a variety of conditions. Several researchers explored specific aspects of dry needling, such as needle placements, whether eliciting a local twitch response is desired, and the role of psychological factors in post-needling soreness. Contributions originated in Australia, Belgium, Brazil, Canada, China, Germany, Greece, India, Israel, Italy, Korea, Portugal, Spain, Switzerland, Turkey, the UK, and the USA.

Dommerholt J, Finnegan M, Hooks T, Chou LW. A critical overview of the current myofascial pain literature - October 2017. J Bodyw Mov Ther. 2017 Oct;21(4):902-913. doi: 10.1016/j.jbmt.2017.08.002. Epub 2017 Aug 18. PMID: 29037647.

ADJUSTING ANUHEA

MATISYAHU- REGGAE/ POP ARTIST- GETTING ADJUSTED

DODGERS GETTING ADJUSTED DODGERS GETTING ADJUSTED

PRO SURFERS GETTING ADJUSTED PRO SURFERS GETTING ADJUSTED CHIROPRACTIC TREATMENT, CONDITIONS, & METHODS RESEARCH ARTICLE TITLE: ALLEVIATION OF PAIN AND DISABILITY IN A POST-SURGICAL C4- C7 TOTAL FUSION PATIENT AFTER REDUCING A LATERAL HEAD TRANSLATION (SIDE SHIFT) POSTURE: A CBP® CASE REPORT WITH A 14 YEAR FOLLOW-UP.

DATE & JOURNAL: J PHYS THER SCI. 2018 JUL

! This case describes the long-term successful outcome in a chronic neck pain patient given Chiropractic Biophysics® treatment 14 years previously, and following surgical fusion of C4-C7 as performed 6.5 years prior to initial presentation. [Participant and Methods] The 56-year-old female had a severe right head translation (side shift) posture and surgical fusion of C4-7 with concomitant head and neck symptoms, high pain and neck disability scores, and low health-related quality of life scores. The patient was treated by Chiropractic BioPhysics methods in an attempt to restore the head and neck posture back towards vertical alignment by mirror image® (opposite posture positioning) exercises, adjustments and traction. [Results] The patient received 25 treatments over the course of 11 days due to special circumstances. Initial treatment resulted in a 50% improvement of posture, a marked improvement in health status and a near complete resolution of pain. Follow-up examinations at 7.5 years, 11.5 years, and 14 years, revealed the patient had lived a virtual pain- free life since those initial treatments. [Conclusion] This case illustrates what has previously been suggested in the literature, that lateral head translation postures can be overlooked and undiagnosed and these postures may play a significant role in the production of neck pain, headaches, and related disability. ARTICLE TITLE: RELIEF OF EXERTIONAL DYSPNEA AND SPINAL PAINS BY INCREASING THE THORACIC KYPHOSIS IN STRAIGHT BACK SYNDROME (THORACIC HYPO-KYPHOSIS) USING CBP® METHODS: A CASE REPORT WITH LONG-TERM FOLLOW-UP.

DATE & JOURNAL: J PHYS THER SCI. 2018 JAN

! To present the clinically significant improvement of straight back syndrome (SBS) in a patient with spinal pain and exertional dyspnea. [Subject and Methods] A 19 year old presented with excessive thoracic hypokyphosis and other postural deviations. A multimodal CBP® mirror image® protocol of corrective exercises, traction procedures and spine/posture adjusting were given over an initial 12-week course of intensive treatment followed by a 2.75 year follow-up with minimal supportive treatment. [Results] The patient had significant postural improvements in all postural measures and specifically a 14° increase in the thoracic kyphosis that was maintained at long-term follow-up. The postural improvements were consistent with relief of exertional dyspnea and pain, as well as increases in both antero-posterior thoracic diameter and the ratio of antero-posterior to transthoracic diameter, measurements critical to the wellbeing of patients with SBS. [Conclusion] Long-term follow-up confirmed stable improvement in physiologic thoracic kyphosis in this patient. Nonsurgical correction in thoracic hypokyphosis/SBS can be achieved by mirror image traction procedures configured to flex the thoracic spine into hyperkyphosis as well as corrective exercise and manipulation as a part of CBP technique protocols. ARTICLE TITLE: THE CBP® MIRROR IMAGE® APPROACH TO REDUCING THORACIC HYPERKYPHOSIS: A RETROSPECTIVE CASE SERIES OF 10 PATIENTS.

DATE & JOURNAL: J PHYS THER SCI. 2018 JAN

! To present a case series demonstrating the reduction of thoracic hyperkyphosis by the Chiropractic BioPhysics® multimodal rehabilitation program. [Participants and Methods] Ten randomly selected files and corresponding radiographs were chosen from recent clinic archives of patients who were treated for thoracic hyperkyphosis. All patients were treated by CBP mirror image® thoracic extension traction and exercises, as well as spinal manipulative therapy. [Results] Results demonstrated an average reduction in hyperkyphosis of 11.3° over an average of 25 treatments, over an average of 9 weeks. Patients also experienced a reduction in pain levels and disability ratings. [Conclusion] Postural hyperkyphosis is a serious progressive deformity that is related to a plethora of symptoms, syndromes, and early death. Thoracic hyperkyphosis may be reduced/corrected by posture-specific, thoracic extension protocols including mirror image extension traction and exercises, as well as spinal manipulation as part of the CBP multi-modal rehabilitation program. ARTICLE TITLE: REDUCTION OF PROGRESSIVE THORACOLUMBAR ADOLESCENT IDIOPATHIC SCOLIOSIS BY CHIROPRACTIC BIOPHYSICS® (CBP®) MIRROR IMAGE® METHODS FOLLOWING FAILED TRADITIONAL CHIROPRACTIC TREATMENT: A CASE REPORT.

DATE & JOURNAL: J PHYS THER SCI. 2017 NOV

! To present a case demonstrating the reduction of progressive thoracolumbar scoliosis by incorporating Chiropractic BioPhysics® (CBP®) technique's mirror image® exercises, traction and blocking procedures based on the 'non-commutative properties of finite rotation angles under addition' engineering law. [Subject and Methods] A 15-year-old female presented with a right thoracolumbar scoliosis having a Cobb angle from T5-L3 of 27° and suffering from headaches and lower back pains. Her curve had progressed over the last two years despite being under traditional chiropractic care. [Results] The patient was treated using CBP structural rehabilitation protocols incorporating mirror image traction, home blocking, corrective exercises and spinal manipulation. The patient was treated 24 times (including 45 home self-treatment blocking sessions) over the course of 15-weeks. Her thoracolumbar curve reduced from 27° to 8° and her headache and low back pain disability improved significantly. [Conclusion] CBP mirror image exercises and traction are consistent with other successful non-surgical approaches and show promise in treating adolescent idiopathic scoliosis. ARTICLE TITLE: ALLEVIATION OF POSTTRAUMATIC DIZZINESS BY RESTORATION OF THE CERVICAL LORDOSIS: A CBP® CASE STUDY WITH A ONE YEAR FOLLOW-UP.

DATE & JOURNAL: J PHYS THER SCI. 2018 MAY

! To present the successful treatment of posttraumatic dizziness and neck pains that were initiated in a patient following a whiplash event. [Subject and Methods] A 46 year old male suffered a whiplash event that initiated neck pain and dizziness symptoms. The patient had many positive orthopedic findings and demonstrated a forward head posture and cervical hypolordosis. The patient was treated by Chiropractic BioPhysics® technique including cervical extension traction, extension exercises and spinal manipulative therapy initially three times a week for 16-weeks, and once a month thereafter. [Results] The patient had a resolution of daily dizziness and neck pain with a concomitant reduction of forward head translation and increase in cervical lordosis. The postural measures were further improved after one year of mostly home-care. [Conclusion] The cervical spine alignment may be an important biomarker for those with dizziness. The correction of cervical lordosis may be an essential requirement for superior clinical outcomes for those with posttraumatic dizziness.

REFERENCES

1. Allen-Unhammer A, Wilson F, Hestbaek L. Children and adolescents presenting to chiropractors in Norway: National Health Insurance data and a detailed survey. Chiropractic & Manual Therapies. 2016;24(1). doi:10.1186/ s12998-016-0107-x.

2. Anstey R, Kongsted A, Kamper S, Hancock M. Are People With Whiplash-Associated Neck Pain Different From People With Nonspecific Neck Pain?. Journal of Orthopaedic & Sports Physical Therapy. 2016;46(10):894-901. doi:10.2519/ jospt.2016.6588.

3. Blanchette M, Stochkendahl M, Borges Da Silva R, Boruff J, Harrison P, Bussières A. Effectiveness and Economic Evaluation of Chiropractic Care for the Treatment of Low Back Pain: A Systematic Review of Pragmatic Studies. PLOS ONE. 2016;11(8):e0160037. doi:10.1371/journal.pone.0160037.

4. du Rose ABreen A. Relationships between Paraspinal Muscle Activity and Lumbar Inter-Vertebral Range of Motion. Healthcare. 2016;4(1):4. doi:10.3390/healthcare4010004.

5. Kendall J, Boyle E, Hartvigsen J et al. Neck pain, concerns of falling and physical performance in community-dwelling Danish citizens over 75 years of age: A cross-sectional study. Scandinavian Journal of Public Health. 2016. doi:10.1177/1403494816666414.

6. 4. Le Clec’h Y, Peterson C, Brunner F, Pfirrmann C. Cervical Facet Joint Imaging-Guided Injections: A Comparison of Outcomes in Patients Referred Based on Imaging Findings Vs Palpation for Pain. Journal of Manipulative and Physiological Therapeutics. 2016;39(7):480-486. doi:10.1016/j.jmpt.2016.06.004. POSTURE & PROPRIOCEPTION RESEARCH ARTICLE TITLE: SUBJECTIVE STABILITY PERCEPTION IS RELATED TO POSTURAL ANXIETY IN OLDER SUBJECTS.

DATE & JOURNAL: GAIT POSTURE. 2019 FEB

! BACKGROUND: Under static conditions, the objective and subjective measures of postural stability correlate well. However, age-related changes in postural control and task-related anxiety may modify the relationship between these subjective and objective measures. Ultimately, patients' symptoms represent subjective reports, thus understanding this relationship has clinical implications.

! AIMS:This study investigates the relationship between subjective-objective measures of postural stability in dynamic conditions and whether this relationship is influenced by age or task-related anxiety.

! METHODS: 50 healthy participants (aged 18-83 years) stood on a platform oscillating at variable amplitudes, with-without a fall-preventing harness to modulate task-related anxiety. Trunk sway path, hip velocity and foot lifts (objective measures) and subjective scores of instability and task-related anxiety were recorded.

! RESULTS: The subjective perception of stability accurately matched objective body sway, following a logarithmic function profile (r2 = 0.72, p < 0.001). This function did not change significantly with age, harness or task presentation order. A strong relationship was observed between subjective measures of stability and task-related anxiety for all subjects (r = 0.81, p < 0.001). Task repetition reduced anxiety in the young, uncoupling anxiety changes from subjective instability, but not in the elderly who retained higher anxiety levels in line with subjective unsteadiness.

! DISCUSSION: Subjects accurately rate their own instability during dynamic postural challenges, irrespective of age and actual fall risk. However, anxiety may selectively modulate the perception of instability in older subjects. The perception of stability relies upon the integration of sensory afferents but also recruits emotional-cognitive processes, particularly in older individuals. The use of a safety harness has no influence on subjective or objective postural stability. ARTICLE TITLE: FLEXED POSTURE IN PARKINSON DISEASE: ASSOCIATIONS WITH NON-MOTOR IMPAIRMENTS AND ACTIVITY LIMITATIONS.

DATE & JOURNAL: PHYS THER. 2019 MAR 4

!BACKGROUND: People with Parkinson disease (PD) are twice as likely to develop flexed truncal posture as the general older population. Little is known about the mechanisms responsible beyond associations with age, axial motor impairments, and disease severity.

!OBJECTIVE: The objective was to explore: (1) the associations of the non-motor impairments of PD with flexed posture and (2) the relationships of flexed posture with activity limitations.

!DESIGN:This was a cross-sectional study.

!METHODS: Seventy people with PD participated. Posture was measured in standing as the distance between the seventh cervical vertebra and a wall. Non-motor impairments (cognition, depression, pain, fatigue, and proprioception) and activity performance (upper limb activity, bed transfers, respiratory function, and speech volume) were variously assessed using objective measures and self-report questionnaires. Univariate and multivariate regression analyses were performed to ascertain relationships between non-motor impairments and truncal posture, as well as between truncal posture and activities.

!RESULTS: Greater disease severity, higher axial impairment, poorer spinal proprioception, greater postural fatigue, and male sex were significantly associated with flexed truncal posture. The multivariate model containing these factors in addition to age explained 31% of the variability in flexed truncal posture, with male sex and axial motor impairment continuing to make independent contributions. A significant association was found between greater flexed truncal posture and poorer upper limb activity performance and respiratory function.

!LIMITATIONS: A limitation to this study was that participants had mild-moderate disease severity.

!CONCLUSIONS: Spinal proprioception and postural fatigue were the only non-motor impairments to make significant contributions to flexed posture. Given the negative influence of flexed posture on upper limb activity and respiratory function, interventions targeting spinal proprioception and postural awareness should be considered for people with PD who may develop flexed posture. ARTICLE TITLE: COMPARISON OF PROPRIOCEPTIVE ACUITY OF THE CERVICAL SPINE IN HEALTHY ADULTS AND ADULTS WITH CHRONIC NON-SPECIFIC LOW BACK PAIN: A CROSS-SECTIONAL STUDY.

DATE & JOURNAL: PLOS ONE. 2019 JAN 10

! BACKGROUND: It has been suggested that patients with chronic non-specific low back pain (CNSLBP) perform poorly in postural tasks when compared to healthy individuals. Despite its importance in posture and alignment of the trunk in relation to the head, neck proprioception has not been examined in patients with low back pain. The purpose of this study was to compare neck proprioception in patients with CNSLBP with healthy individuals.

! METHODS: Cervical joint reposition error was measured five times consecutively in the neutral head position, 30° and 60° left and right head rotation. The main outcome measure was the mean cervical joint repositioning error of the head.

! RESULTS: Forty-six participants with (n = 24, 54 ± 16yrs SD, 14 females) and without (n = 22, 36 ± 13yrs SD, 13 females) CNSLBP were included in the study. Comparison of mean cervical joint repositioning error between patients and healthy controls showed no statistically significant group difference in any of the applied positions. The range of deviation in CNSLBP patients was between 1.57° and 3.27° compared to 1.46° to 2.26° in healthy controls. An overshooting tendency for both groups was found in the neutral head position.

! CONCLUSION:The ability to accurately position the head does not seem to be impaired in patients with CNSLBP. This may suggest that sensorimotor control is affected on other levels of the movement system and future research should focus on methods to identify the source of these aberrations. ARTICLE TITLE: CHARACTERIZATION OF CERVICAL SPINE IMPAIRMENTS IN CHILDREN AND ADOLESCENTS POST-CONCUSSION.

DATE & JOURNAL: INT J SPORTS PHYS THER. 2019 APR;14

! BACKGROUND: Patients with concussion may present with cervical spine impairments, therefore accurate characterization of cervical post-concussion impairments is needed to develop targeted physical therapy interventions. ! PURPOSE:To characterize the type, frequency and severity of cervical impairments in children and adolescents referred for physical therapy after concussion.Study design: Retrospective, descriptive study. ! METHODS:A retrospective analysis was conducted for 73 consecutive children and adolescents who received cervical physical therapy following a concussion. Data was classified into six broad categories. The frequency and intensity of cervical impairments within and across the categories was reported. ! RESULTS:Ninety percent of patients demonstrated impairments in at least three out of five assessment categories whereas 55% demonstrated impairments in at least four out five assessment categories. Of the five assessment categories, posture (99%) and myofascial impairment (98%) demonstrated highest impairment frequency followed by joint mobility (86%) and muscle strength (62%). Cervical joint proprioception was the least commonly evaluated assessment category. ! CONCLUSION:High prevalence of cervical spine impairments was observed in the subjects included in this study with muscle tension, joint mobility, and muscle strength being most commonly affected. The categories of impairments examined in this cohort were consistent with the recommendations of the most recent clinical practice guidelines for neck pain. This study provides preliminary data to support the framework for a cervical spine evaluation tool in children and adolescents following concussion. PROPRIOCEPTIVE MUSCLE TENDON STIMULATION REDUCES SYMPTOMS IN PRIMARY ORTHOSTATIC TREMOR

!INTRODUCTION:Primary orthostatic tremor (OT) is characterized by high-frequency lower limb muscle contractions and a disabling sense of unsteadiness while standing. To date, therapeutic options for OT are limited. Here, we examined the effects of proprioceptive leg muscle stimulation via muscle tendon vibration (MTV) on tremor and balance control in patients with primary OT. !RESULTS:During standing, all patients showed a coherent high-frequency tremor in leg muscles and body sway that was absent during lying (p < 0.001). MTV during standing did not reset tremor frequency, but resulted in a decreased tremor intensity (p < 0.001; mean reduction: 32.5 ± 7.1%) and body sway (p = 0.032; mean reduction: 37.2 ± 6.8%). MTV did not affect muscle activity during lying. Four patients further reported a noticeable relief from unsteadiness during stimulation. !CONCLUSION:Proprioceptive stimulation did not reset tremor frequency consistent with the presumed central origin of OT. However, continuous MTV influenced the emergence of OT symptoms resulting in reduced tremor intensity, improved posture, and a relief from unsteadiness in half of the examined patients. These findings indicate that MTV either directly interferes with the peripheral manifestation of the central oscillatory pattern or prevents proprioceptive afferent feedback from becoming extensively synchronized at the tremor frequency.

J Neurol. 2018 May 16. doi: 10.1007/s00415-018-8902-z. REFERENCES

1. Arvin M, van Dieën J, Faber G, Pijnappels M, Hoozemans M, Verschueren S. Hip abductor neuromuscular capacity: A limiting factor in mediolateral balance control in older adults?. Clinical Biomechanics. 2016;37:27-33. doi:10.1016/j.clinbiomech.2016.05.015.

2. 2. Arvin M, van Dieën J, Faber G, Pijnappels M, Hoozemans M, Verschueren S. Hip abductor neuromuscular capacity: A limiting factor in mediolateral balance control in older adults?. Clinical Biomechanics. 2016;37:27-33. doi:10.1016/j.clinbiomech.2016.05.015.

3. Hincapie O, Elkins J, Vasquez-Welsh L. Proprioception retraining for a patient with chronic wrist pain secondary to ligament injury with no structural instability. Journal of Hand Therapy. 2016;29(2):183-190. doi:10.1016/j.jht.2016.03.008.

4. Huang C, Chang G, Tsai Y, Hwang I. An Increase in Postural Load Facilitates an Anterior Shift of Processing Resources to Frontal Executive Function in a Postural-Suprapostural Task. Frontiers in Human Neuroscience. 2016;10. doi:10.3389/fnhum.2016.00420. FORWARD HEAD POSTURE RESEARCH

ARTICLE TITLE: ALLEVIATION OF CHRONIC SPINE PAIN AND HEADACHES BY REDUCING FORWARD HEAD POSTURE AND THORACIC HYPERKYPHOSIS: A CBP® CASE REPORT.

DATE & JOURNAL: J PHYS THER SCI. 2018 AUG

! This case presents the reduction of both forward head posture and thoracic hyperkyphosis in a young male with chronic back pain and headaches by a comprehensive posture rehabilitation program as a part of Chiropractic BioPhysics® methods. [Participant and Methods] A 32 year old male presented with constant pain and headaches for seven years since he was involved in a work related injury. He had seen five different MDs, undergone multiple imaging tests, and received multiple prescriptions, thirteen steroid injections and was recommended for a spine surgery that he had denied. He was on long-term disability. Upon comprehensive posture and spine assessment, the patient had exaggerated forward head translation and thoracic hyperkyphosis. The patient was treated 36 times over 13-weeks with cervical and thoracic extension exercises, traction, and manipulation. [Results] After treatment the patient reported dramatic improvement in symptoms as indicated on valid disability questionnaires and substantial improvements in posture. [Conclusion] Posture-related pain and disability is not often addressed in allopathic medicine but substantial posture improvements are achievable in short time periods as this case illustrates. Poor postures in young patients should be corrected to avoid long-term consequences. Radiography as used in spinal rehabilitation is safe and reliable. ARTICLE TITLE: IMPROVING POSTURE TO REDUCE THE SYMPTOMS OF PARKINSON'S: A CBP® CASE REPORT WITH A 21 MONTH FOLLOW-UP.

DATE & JOURNAL: J PHYS THER SCI. 2019 FEB

! To demonstrate the reduction of symptoms related to Parkinson's disease by improvement in posture. [Participant and Methods] A 59-year-old male patient presented with a prior diagnosis of Parkinson's. Symptoms included a resting right hand tremor, intermittent 'freezing episodes' with gait, mild ataxia with shuffling on toes and bradykinesia assisted with a cane, as well as low back pain and right knee pain. Radiography revealed gross postural and spine deformity. The patient received Chiropractic BioPhysics care including mirror image exercises, spinal traction, spinal adjustments as well as gait rehabilitation. [Results] After 38 treatments over 5 months, the patient had significant improvements in posture alignment as well as gait, balance, hand tremors, low back and knee pains and SF-36 values. A 21 month follow-up revealed the patient had remained essentially well and the initial postural improvements were maintained. [Conclusion] This case demonstrates improvement of various symptoms in a patient with Parkinson's disease. Since poor posture is a long known clinical manifestation of this disorder, it is proposed that the improvement of posture in these patients may lead to improved outcomes. X-ray use in the diagnosis and management in those with spine deformity is safe and not carcinogenic. ARTICLE TITLE: NON-SURGICAL RELIEF OF CERVICAL RADICULOPATHY THROUGH REDUCTION OF FORWARD HEAD POSTURE AND RESTORATION OF CERVICAL LORDOSIS: A CASE REPORT.

DATE & JOURNAL: J PHYS THER SCI. 2017 AUG

! To present a case demonstrating the relief of cervical radiculopathy following the dramatic reduction of forward head posture and restoration of the cervical lordosis by use of a multi-modal rehabilitation program incorporating cervical extension traction. [Subject and Methods] A 31-year-old male patient presented with severe cervical radiculopathy and muscle weakness as well as neck pain. The patient had limited neck range of motion, and multiple positive orthopedic tests. Radiography revealed excessive forward head posture with a cervical kyphosis. [Results] The patient received a multi-modal rehabilitation protocol including mirror image extension exercises, cervical extension traction, and spinal manipulative therapy. After forty treatments over 17 weeks, the patient reported a complete resolution of radiculopathy and significant improvement in neck pain level. Post radiography demonstrated correction of the spine and posture alignment. The patient remained well and maintained corrected posture with limited treatment one year later. [Conclusion] Our case demonstrates the relief of cervical radiculopathy resulting from the non-surgical correction of forward head posture and cervical kyphosis. CHIROPRACTIC CURRENT LITERATURE REVIEW ARTICLE TITLE: HIGH-VELOCITY, LOW-AMPLITUDE SPINAL MANIPULATION TRAINING OF PRESCRIBED FORCES AND THRUST DURATION: A PILOT STUDY.

DATE & JOURNAL: J CHIROPR EDUC. 2019 APR 5

!OBJECTIVE:: High-velocity, low-amplitude spinal manipulation (HVLA-SM) may generate different therapeutic effects depending on force and duration characteristics. Variability among clinicians suggests training to target specific thrust duration and force levels is necessary to standardize dosing. This pilot study assessed an HVLA-SM training program using prescribed force and thrust characteristics.

!METHODS:: Over 4 weeks, chiropractors and students at a chiropractic college delivered thoracic region HVLA-SM to a prone mannequin in six training sessions, each 30 minutes in duration. Force plates embedded in a treatment table were used to measure force over time. Training goals were 350 and 550 Newtons (N) for peak force and ≤150 ms for thrust duration. Verbal and visual feedback was provided after each training thrust. Assessments included 10 consecutive thrusts for each force target without feedback. Mixed-model regression was used to analyze assessments measured before, immediately following, and 1, 4, and 8 weeks after training.

!RESULTS:: Error from peak force target, expressed as adjusted mean constant error (standard deviation), went from 107 N (127) at baseline, to 0.2 N (41) immediately after training, and 32 N (53) 8 weeks after training for the 350 N target, and 63 N (148), -6 N (58), and 9 N (87) for the 550 N target. Student median values met thrust duration target, but doctors' were >150 ms immediately after training.

!CONCLUSION::After participation in an HVLA-SM training program, participants more accurately delivered two prescribed peak forces, but accuracy decreased 1 week afterwards. Future HVLA-SM training research should include follow-up of 1 week or more to assess skill retention. ARTICLE TITLE: EFFECT OF CERVICAL MANIPULATION ON VERTEBRAL ARTERY AND CEREBRAL HAEMODYNAMICS IN PATIENTS WITH CHRONIC NECK PAIN: A CROSSOVER RANDOMISED CONTROLLED TRIAL.

DATE & JOURNAL: BMJ OPEN. 2019 MAY 28

! OBJECTIVE: It is hypothesised that cervical manipulation may increase the risk of cerebrovascular accidents. We aimed to determine whether cervical spine manipulation is associated with changes in vertebral artery and cerebrovascular haemodynamics measured with MRI compared with neutral neck position and maximum neck rotation in patients with chronic neck pain.

! INTERVENTIONS:Following baseline measurement of cerebrovascular haemodynamics, we randomised participants to: (1) maximal neck rotation followed by cervical manipulation or (2) cervical manipulation followed by maximal neck rotation. The primary outcome, vertebral arteries and cerebral haemodynamics, was measured after each intervention and was obtained by measuring three- dimensional T1-weighted high-resolution anatomical images, arterial spin labelling and phase-contrast flow encoded MRI. Our secondary outcome was functional connectivity within the default mode network measured with resting state functional MRI.

! RESULTS:Compared with neutral neck position, we found a significant change in contralateral blood flow following maximal neck rotation. There was also a significant change in contralateral vertebral artery blood velocity following maximal neck rotation and cervical manipulation. We found no significant changes within the cerebral haemodynamicsfollowing cervical manipulation or maximal neck rotation. However, we observed significant increases in functional connectivity in the posterior cerebrum and cerebellum (resting state MRI) after manipulation and maximum rotation.

! CONCLUSION:Our results are in accordance with previous work, which has shown a decrease in blood flow and velocity in the contralateral vertebral artery with head rotation. This may explain why we also observed a decrease in blood velocity with manipulation because it involves neck rotation. Our work is the first to show that cervical manipulationdoes not result in brain perfusion changes compared with a neutral neck position or maximal neck rotation. The changes observed were found to not be clinically meaningful and suggests that cervical manipulation may not increase the risk of cerebrovascular events through a haemodynamic mechanism. ARTICLE TITLE: THE IMPACT OF SPINAL MANIPULATION ON MIGRAINE PAIN AND DISABILITY: A SYSTEMATIC REVIEW AND META-ANALYSIS.

DATE & JOURNAL: HEADACHE. 2019 APR

!BACKGROUND: Several small studies have suggested that spinal manipulation may be an effective treatment for reducing migraine pain and disability. We performed a systematic review and meta-analysis of published randomized clinical trials (RCTs) to evaluate the evidence regarding spinal manipulation as an alternative or integrative therapy in reducing migraine pain and disability.

!METHODS: PubMed and the Cochrane Library databases were searched for clinical trials that evaluated spinal manipulation and migraine-related outcomes through April 2017. Search terms included: migraine, spinal manipulation, manual therapy, chiropractic, and osteopathic. Meta-analytic methods were employed to estimate the effect sizes (Hedges' g) and heterogeneity (I2 ) for migraine days, pain, and disability. The methodological quality of retrieved studies was examined following the Cochrane Risk of Bias Tool.

!RESULTS: Our search identified 6 RCTs (pooled n = 677; range of n = 42-218) eligible for meta-analysis. Intervention duration ranged from 2 to 6 months; outcomes included measures of migraine days (primary outcome), migraine pain/intensity, and migraine disability. Methodological quality varied across the studies. For example, some studies received high or unclear bias scores for methodological features such as compliance, blinding, and completeness of outcome data. Due to high levels of heterogeneity when all 6 studies were included in the meta-analysis, the 1 RCT performed only among chronic migraineurs was excluded. Heterogeneity across the remaining studies was low. We observed that spinal manipulation reduced migraine days with an overall small effect size (Hedges' g = -0.35, 95% CI: -0.53, -0.16, P < .001) as well as migraine pain/intensity.

!CONCLUSIONS:Spinal manipulation may be an effective therapeutic technique to reduce migraine days and pain/intensity. However, given the limitations to studies included in this meta-analysis, we consider these results to be preliminary. Methodologically rigorous, large-scale RCTs are warranted to better inform the evidence base for spinal manipulation as a treatment for migraine. ARTICLE TITLE: MANIPULATION AND MOBILIZATION FOR TREATING CHRONIC NONSPECIFIC NECK PAIN: A SYSTEMATIC REVIEW AND META-ANALYSIS FOR AN APPROPRIATENESS PANEL.

DATE & JOURNAL: PAIN PHYSICIAN. 2019 MAR

!BACKGROUND: Mobilization and manipulation therapies are widely used by patients with chronic nonspecific neck pain; however, questions remain around efficacy, dosing, and safety, as well as how these approaches compare to other therapies.

!OBJECTIVES: Based on published trials, to determine the efficacy, effectiveness, and safety of various mobilization and manipulation therapies for treatment of chronic nonspecific neck pain.

!RESULTS: A total of 47 randomized trials (47 unique trials in 53 publications) were included in the systematic review. These studies were rated as having low risk of bias and included a total of 4,460 patients with nonspecific chronic neck pain who were being treated by a practitioner using various types of manipulation and/or mobilization interventions. A total of 37 trials were categorized as unimodal approaches and involved thrust or nonthrust compared with sham, no treatment, or other active comparators. Of these, only 6 trials with similar intervention styles, comparators, and outcome measures/timepoints were pooled for meta-analysis at 1, 3, and 6 months, showing a small effect in favor of thrust plus exercise compared to an exercise regimen alone for a reduction in pain and disability. Multimodal approaches appeared to be effective at reducing pain and improving function from the 10 studies evaluated. Health-related quality of life was seldom reported. Some 22/47 studies did not report or mention adverse events. Of the 25 that did, either no or minor events occurred.

!LIMITATIONS: The current evidence is heterogeneous, and sample sizes are generally small.

!CONCLUSIONS: Studies published since January 2000 provide low-moderate quality evidence that various types of manipulation and/or mobilization will reduce pain and improve function for chronic nonspecific neck pain compared to other interventions. It appears that multimodal approaches, in which multiple treatment approaches are integrated, might have the greatest potential impact. The studies comparing to no treatment or sham were mostly testing the effect of a single dose, which may or may not be helpful to inform practice. According to the published trials reviewed, manipulation and mobilization appear safe. However, given the low rate of serious adverse events, other types of studies with much larger sample sizes would be required to fully describe the safety of manipulation and/or mobilization for nonspecific chronic neck pain. UPDATE! LICENSE RENEWAL NOW AVAILABLE ONLINE!!!

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STROKE RESEARCH I. Boundaries Issues Ethics & Law A.For Healthcare Providers 1.Professional Boundaries 2.Mandatory Reporting Requirements B.State Board Laws, Rules, and Regulations overview 1.Informed Consent and waivers 2.Common Violations of the SBCE C. Pandemic protocols for Healthcare Providers using CDC, state, and federal guidelines TOP 10 BOARD DISCIPLINARY ACTIONS TOP 10 BOARD DISCIPLINARY ACTIONS

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