In the News

BRYAN NITRICEUTICALS LLC and TEXAS PHILANTHROPIST Donate $790,000 Worth of NITRIC OXIDE Products to NEPAL For COVID Crisis

What you need to know about the delta variant

Half of pediatric opioid prescriptions are 'high risk'

Prevent diabetes misdiagnosis, mismanagement through precision medicine

Age-related decline in two sirtuin enzymes alters mitochondrial dynamics, weakens cardiac contractions

BRYAN NITRICEUTICALS LLC and TEXAS PHILANTHROPIST Donate $790,000 Worth of NITRIC OXIDE Products to NEPAL For COVID Crisis

Bryan Nitriceuticals, LLC, a Texas Based Company, along with Texas Philanthropist donate $790,000 worth of Nitric Oxide (NO) products to the people of Nepal, to help in the COVID crisis, proudly announced today by Founder Nathan S. Bryan Ph.D.  Dr. Bryan and Bryan Nitriceuticals, LLCare represented by Alan Morell, Creative Management Partners LLC.
With the initiation of Basanta Chaudhary Foundation and Norvic Initiatives for Nutrition and Health, Former Senator of Texas,Mr. Dan Shelley, along with Bryan Nitriceuticals LLC Founder Dr. Nathan Bryan, (the inventor of the NO dietary supplement, the company that manufactures and distributes the lozenge), has come to Kathmandu, Nepal to officially donate 10,000 bottles of NO2U, a Nitric Oxide dietary supplement, valued at over $790,000 to the people of Nepal in a humanitarian effort to provide immune support to at risk patients. 
Senator Shelley Said: “I could not ignore the news stories revealing the COVID cases and deaths in Nepal. I have close friends in Nepal and believe this Nitric Oxide (NO) supplement will provide safe and effective solutions for at-risk patients to the masses, including the people of Nepal.”
Expecting the third wave of COVID-19 infection, various stakeholders are preparing to tackle the spread through different approaches and conducting research. In this regard, scientists have identified the risks of spreading of the infection, hospitalization, and death. 
Said Founder Nathan S. Bryan PH.D: “COVID-19 has transformed the global economy and the global health care system.  Nepal is one of the hardest hit areas with currently around 3,000 new cases each day and over 700,000 total cases with over 10,000 deaths in such a small country. At Bryan Nitriceuticals, LLC, we are dedicated to saving lives globally and this donation was a small part of our dedication of giving back. Over the past 19 months, everything we have learned about COVID reveals that it is a disease of Nitric Oxide deficiency.  Similar to strategies of supplementing zinc, Vitamin D and Vitamin C to at-risk or infected COVID patients, we can supplement with Nitric Oxide as a means to support blood flow, circulation and normalize oxygen carrying capacity of our red blood cells. We recognize the importance of Nitric Oxide in COVID and we also recognize the global need for safe and effective strategies to combat against this global pandemic, especially in regions that may not have access to same medical care as in the U.S.  We will do whatever we can to help the people of Nepal and elsewhere around the globe.  We have the product technology and the science to help at-risk patients.  Government leaders were very supportive and enthusiastic about our Nitric Oxide product technology.”
SCIENTIFIC STUDIES / NITRIC OXIDE (NO):
It is recognized scientifically that patients with the highest risk of infection, rapid progression of disease leading to hospitalization, ventilation and death suffer from endothelial dysfunction and lack of production of Nitric Oxide (NO). Studies have shown that humans with hypertension, diabetes, obesity, kidney related diseases, heart diseases and smokers have less capacity to produce Nitric Oxide in the body. These categories of people are at more risk to COVID-19 infection and rapid progression of the disease. 
NO is a naturally produced molecule which is very important to the human body. NO is responsible for the management of blood pressure and oxygen saturation in the blood. Furthermore, NO is also involved in reducing inflammation, studies have shown it inhibits Corona virus replication and NO has protective roles against several infections including COVID-19.    
ABOUT NATHAN S. BRYAN PH.D:       
Dr. Bryan earned his undergraduate Bachelor of Science degree in Biochemistry from the University of Texas at Austin and his doctoral degree from Louisiana State University Health Sciences Center in Shreveport.  He pursued his post-doctoral training as a Kirschstein Fellow at Boston University School of Medicine in the Whitaker Cardiovascular Institute.  Most recently, Dr. Bryan serves as Founder and CEO of Nitric Oxide Innovations, LLC, a privately-held, clinical-stage biopharmaceutical company that is actively engaged in the discovery and development of nitric oxide based drug therapies.  Their lead drug candidate NOviricid is currently in phase 3 clinical trials for the treatment of COVID19 in African Americans. 
About Bryan Nitrceuticals LLC:  
Bryan Nitriceuticals, LLC is a nitric oxide focused nutrition and dietary supplement company that provides safe and effective nitric oxide functional food products and dietary supplements.  Bryan Nitriceuticals LLC was founded by Dr. Nathan S. Bryan, international leader in Nitric Oxide biochemistry and product technology.  Their NO2U lozenge is a safe and potent Nitric Oxide delivery system that helps support Nitric Oxide repletion and production.  Bryan Nitriceuticals LLCs donates 5% of their profits to humanitarian causes across the globe.   
For further information go to: www.bryannitriceuticals.com

What you need to know about the delta variant

For more than 40 years, UCI infectious disease researcher Michael Buchmeier has studied coronaviruses, and he’s one of the leading experts on SARS-CoV-2, the version of the virus causing the COVID-19 pandemic. As a more lethal mutation of the virus, called the delta variant, sparks another wave of cases, he offers his expertise about this threat.
How does the delta variant differ from the original form of the COVID-19 coronavirus?
The form of the original coronavirus is really not clear. If, as we think, SARS-CoV-2 appeared in humans after jumping from an animal host, such as a bat, then the sequence may have already contained mutations in its genome that allowed that species jump. Many of the so-called emerging diseases represent jumps from a zoonotic animal host to humans.
The power of this genetic flexibility is characteristic of RNA viruses. This flexibility results in the production of a swarm of related viral “offspring” at each round of replication, allowing the virus to select a genetic makeup best adapted to a given host in the form of the variant viruses we’re now experiencing.
Mutations are always present in the progeny viruses and may be selected if there’s an advantage offered for replication in a new host species. The current variants of SARS-CoV-2 – which include the B.1.1.7 (alpha), B.1.351 (beta), B.1.617.2 (delta) and P.1 (gamma) variants circulating in the United States – are classified as variants of concern. Beta, delta and gamma are derived from the alpha virus, which was first described in the U.K. in 2020.
What makes the delta variant more contagious and virulent than the previous version?
Current research based on observation of patients infected with the delta variant shows that it may produce as much as 1,000 times more virus in the nasal passages and upper respiratory tract early in the infection, when people may not exhibit overt symptoms. This offers two advantages for viral spread: First, the spread of the virus in droplets from the upper respiratory tract is facilitated by the larger amount of infectious virus in the nasal secretions; and second, the immune response is not as robust in that location as it is in the lower respiratory tract. This combination leads to a high proportion of asymptomatic carriers who can spread the infection to others. Vaccination acts to protect these individuals from a severe reaction to the disease, which requires hospitalization and may result in death. Recent data indicates that less than 1 percent of newly hospitalized patients have been fully vaccinated.
Can vaccination effectively mitigate the spread of the delta variant?
Vaccines are not designed to prevent infection but to prevent disease. The evidence with the delta variant shows that vaccines are very effective at preventing severe disease and hospitalization.
The question I’m often asked is how the vaccines work. They “educate” the immune system with exposure to critical viral proteins made during the life cycle of the virus. In the case of SARS-CoV-2 and COVID-19, the protein spike that allows the virus to enter cells is the protein targeted by the introduction of a viral RNA message that directs the synthesis of the spike protein in the absence of virus replication. The result of this exposure is a robust immune response. In this way, the vaccination is able to “prime” the immune response to combat the virus with antibodies and T-cells at the time of infection without the normal delay. In this case, the vaccination is designed to quell any new infection, usually without symptoms. Each viral exposure serves to restimulate, or boost, the immune response protection it affords. The net result is to mitigate the spread of infection.
Do you see the COVID-19-causing coronavirus circulating like influenza each year?
It appears that the SARS-CoV-2 virus has been established as part of the human virome – which is the total collection of viruses in and on the human body – and will persist. The virus has spread rapidly among widely dispersed human populations. It has shown the ability to mutate to fine-tune and sustain the infectious cycle through several cycles of infection in humans and animals. Viral variants have arisen and will continue to appear, and some of these will be more capable of spreading. It’s possible that the virus may become less virulent for humans but, like the common cold coronaviruses, still persist. Finally, precursors of SARS-CoV-1 and SARS-CoV-2 exist in bats and may provide a reservoir for future cycles of human infection.
Research efforts will continue to provide the means to control this virus, as we have done for polio and smallpox, both of which were controlled in the 1950s and 1970s. The principal difference with SARS-CoV-2 is that the virus has an animal reservoir in the Asian horseshoe bat and is capable of reemergence. This is also the case with influenza, which persists in waterfowl and is amplified in swine. The genetics of influenza are dictated by the host, with mammalian strains being selected by passage through the pig. If it’s shown that the SARS-CoV-2 virus – like the flu virus – requires an intermediate host to make the jump from bat to human, then immunization of that host may be effective.
Are we facing a prolonged fourth wave of COVID-19 as we enter the fall?
Earlier in 2021, it appeared that the pandemic was on the verge of being controlled, but it was replaced by the fourth wave of COVID-19 cases that we’re now experiencing. The clear message is that as long as vaccination of populations remains incomplete and clearly effective social distancing and masking are not observed, we’re very likely to see more waves.
Source: University of California, Irvine

Half of pediatric opioid prescriptions are 'high risk'

Children and young adults who have pain from surgery, dental care and other conditions are often prescribed opioids.
But half of these prescriptions, a new national study suggests, are high risk because of their potential for adverse outcomes.
What's more, a small group of prescribers in the top 5% of prescriptions account for half of all opioid prescriptions for children and young adults and half of high risk prescriptions. Many of these prescribers are dentists or surgeons, and a disproportionate share practice in the South, according to the study in Pediatrics.
Researchers analyzed roughly four million opioid prescriptions dispensed to kids and young adults under age 21 in 2019. Prescriptions that exceeded a recommended supply or dose or included a drug or combination of drugs not recommended for children were considered high risk.
"Our study suggests that children and young adults are frequently exposed to unsafe opioid prescriptions, increasing their risk of overdose, misuse, and addiction," said lead author Kao-Ping Chua, M.D., Ph.D., a pediatrician and researcher at University of Michigan Health C.S. Mott Children's Hospital and the Susan B. Meister Child Health Evaluation and Research Center.
"The fact that these prescriptions were so heavily concentrated among a small group of prescribers suggests that quality improvement efforts should target these prescribers."
The most common types of high-risk opioid prescriptions were those for acute pain and that went beyond three or seven days. A three-day supply is usually enough for acute pain and prescriptions exceeding seven days are rarely necessary, according to the Centers for Disease Control and Prevention.
"Many of these prescriptions were likely for dental and surgical procedures that don't require long durations of opioid therapy," Chua said. "There have been successful efforts to reduce opioid quantities for adult surgery patients through evidence-based prescribing guidelines. Similar efforts have begun in some pediatric institutions but should be more widespread."
About one in six prescriptions dispensed to young children aged 0 to 11 included codeine or tramadol. The U.S. Food and Drug Administration has explicitly warned against using these drugs in young children due to reports of fatal overdose.
The persistent use of codeine is consistent with Chua's previous research revealing incomplete reductions in codeine prescribing to children undergoing tonsil removal after an FDA black box warning in 2013.
To minimize prescribing of codeine and tramadol to young children, he said, electronic health record systems and pharmacists could prompt clinicians to consider alternatives when they attempt to prescribe these medications. Insurers could also refuse to cover such prescriptions for young children.
Nearly 12% of opioid prescriptions dispensed to adolescents and young adults aged 12 to 21 years were also considered high risk because they exceeded recommended daily dosages of opioids.
Another nearly 5% overlapped with benzodiazepines, central nervous system depressants frequently prescribed for anxiety, stress attacks and sleep disorders. Chua's prior work has shown that this overlap greatly increases overdose risk in adolescents and young adults.
Dentists and surgeons play an outsized role in prescribing
Sixty one percent of opioid prescriptions to children and young adults were from dentists or surgeons. However, Chua's research has found that opioids are commonly overprescribed to young people after dental and surgical procedures.
For example, one of his studies found that almost 80% of dental opioid prescriptions for adolescents and young adults are for tooth extraction, a procedure for which ibuprofen provides effective relief.
Another of his studies found that six in 10 privately insured children undergoing tonsillectomy are prescribed opioids, even though randomized trials show ibuprofen provides equal pain control.
"Avoiding unnecessary opioid prescribing not only decreases the risk of misuse and overdose but also lowers the risk of side effects, such as vomiting and constipation," Chua said. "For many dental and surgical procedures, reducing opioid prescribing could improve patient experience without compromising pain control."
Co-authors of the study included Chad Brummett, M.D., and Amy Bohnert, Ph.D., M.H.S., of the U-M Department of Anesthesiology; and Rena Conti, Ph.D., of the Boston University Questrom School of Business.
Source: Michigan Medicine - University of Michigan.

Prevent diabetes misdiagnosis, mismanagement through precision medicine

Precision medicine via genetic testing and family history can reduce uncertainty in diabetes diagnoses and allow more targeted therapy, improving patient-centered outcomes, such as mental health and quality of life, according to a speaker.
“A common example of precision medicine in diabetes care is to tailor diabetes medications based on genetic testing for monogenic diabetes,” Julia Blanchette, PhD, RN, CDCES, a postdoctoral research fellow in integrated diabetes management at the University of Utah College of Nursing, told Healio. “However, precision medicine goes beyond one classification of diabetes and has the potential to be applied to type 1 and type 2 diabetes treatment as well.”
Growing data show that there are likely many types of diabetes beyond the type 1 and type 2 classifications, Blanchette said during a virtual presentation at the Association of Diabetes Care & Education Specialists Annual Conference. Preventing misdiagnosis and mismanagement of diabetes can reduce frustration and diabetes distress, and allow more effective treatments, she said.
“We can also use pharmacogenetics here, which focuses on identifying which patients are most likely to benefit from a drug or which are most likely to avoid adverse effects based on one’s pharmacodynamics and pharmacokinetic responses,” Blanchette said. “There are also polymorphisms in drug targets that can affect therapeutic outcomes.”
Treatments can also be tailored to avoid adverse effects, Blanchette said.
“We can use precision medicine database generation programs that look at genetic, biomarker, environmental and behavioral data, and we can develop diabetes classification models that simplify the treatment regimen and provide the best combination of efficacy and unlikely adverse effects,” Blanchette said. “Further down the line, we can also simplify treatment regimens by using medications that fit that profile and reducing the number of medications that one is [prescribed].”
Genetic testing offers many advantages for disease management, though it currently comes with several barriers, Blanchette said — cost of genetic screenings can run about $4,000 when not approved by insurance.
“When you get into genetic testing, the lab draws and then the genetic interpretation can be costly out of pocket; however, with prior authorization, insurance coverage usually happens, and it is continuing to expand,” Blanchette said. “The cost for out of pocket has decreased significantly, even in the past 5 years alone.”
When genetic testing is out of reach, providers can also use biomarker testing, such as type 1 diabetes autoantibody testing, to help identify disease risk, Blanchette said.
“We can even use these tests at home these days,” Blanchette said. “These are very affordable options, at only $40 to $50 out of pocket.”
Ethnic bias is another challenge with genetic testing beyond diabetes; in 2009, 96% of all genomic studies were among European populations. That number fell only slightly by 2016 to 81%, with primarily Asian groups making up the underrepresented populations, Blanchette said.
“The reason this impacts precision medicine in diabetes specifically is that diabetes phenotypes can vary, especially among different ethnic backgrounds,” Blanchette said. “Right now, this data may not be widely generalizable due to a lack of heterogeneity.”
Many people from historically marginalized groups are rightly concerned about providing genetic data because of a long history of violations of trust, Blanchette said. To increase diversity in genetic data, Blanchette said, researchers must “cultivate trust” by developing relationships with marginalized communities; engaging concerns about risks, stigmatization and discrimination; and integrating participants’ values and expectations.
“Precision medicine has significant potential to better the lives and care of people living with diabetes,” Blanchette told Healio. “We need to continue educating diabetes clinicians and people with diabetes about the benefits of precision medicine in diabetes, to continue research, and to reduce health care disparities and cost as barriers to wide implementation.”

Source: Blanchette J. D11. Presented at: ADCES21; Aug. 12-15, 2021 (virtual meeting).

Age-related decline in two sirtuin enzymes alters mitochondrial dynamics, weakens cardiac contractions

Sirtuins are a family of anti-aging proteins that help regulate cellular lifespan, metabolism, and resistance to stress. The potential protective effect of these sirtuin enzymes in age-related diseases, including cardiovascular diseases, remains an area of intense investigation.
Now, a new preclinical study led by University of South Florida Health (USF Health) researchers has determined that sirtuin 1 (SIRT1) and sirtuin 3 (SIRT3) levels decline in aging hearts, disrupting the ability of cardiac muscle cells (cardiomyocytes) to contract in response to ischemia-reperfusion injury (also known as reperfusion injury). Furthermore, age-related SIRT1 and SIRT3 deficiency can impair cardiac function by altering mitochondrial dynamics, which play an important role in metabolic health and inflammatory response, the researchers report.
The findings were published online July 3 in Aging Cell.
"We discovered that age-related changes in mitochondrial dynamics are caused by SIRT1/SIRT3 deficiency, specifically in the cardiomyocytes," said principal investigator Ji Li, PhD, professor of surgery in the USF Health Morsani College of Medicine. "You need a strong presence of SIRT1 and SIRT3 to keep mitochondrial dynamics healthy in the heart. Otherwise, the heart's pumping function becomes weak."
Mitochondria produce the energy needed to drive nearly all processes in living cells. Cardiac muscle cells contain more mitochondria than any other cells, because the heart needs large amounts of energy to constantly pump blood throughout the body. Stabile mitochondrial dynamics maintain a healthy balance between the constant division (fission) and merging (fusion) of mitochondria and help ensure the quality of these specialized structures known as the "powerhouse" of the cell.
Reperfusion, a common treatment following acute heart attack, restores blood flow (and thus oxygen) to a region of the heart damaged by a blood clot blocking the coronary artery. Paradoxically, in some patients this necessary revascularization procedure triggers further injury to heart muscle tissue surrounding the initial heart attack site. No effective therapies currently exist to prevent reperfusion injury.
To help analyze the response of cardiac mitochondria to ischemia-reperfusion stress, the USF Health researchers deleted SIRT1 or SIRT3 in cardiac muscle cells of mouse hearts, and examined the mitochondrial response to ischemic stress by restricted blood flow. The researchers found that the mitochondria in mouse hearts lacking cardiomyocyte SIRT3 were more vulnerable to reperfusion stress than the mouse hearts with SIRT3 intact. The cardiac mitochondrial dynamics (including shape, size, and structure of mitochondria) in these knockout mice physiologically resembled that of aged wildtype (normal) mice retaining cardiac SIRT3.
Furthermore, the young mice with SIRT1 or SIRT3 removed had measurably weaker cardiomyocyte contractions and exhibited aging-like heart dysfunction when ischemia-reperfusion stress was introduced. In essence, without SIRT1/SIRT3 the hearts of these otherwise healthy young mice looked and behaved like old hearts.
"We started this study trying to understand why older people have higher incidence of heart attacks than younger people, and why they die more often even if they receive maximum treatment. Younger people are much more likely to recover from heart attacks and less likely to suffer from ischemia-reperfusion injury," said Dr. Li, a member of the USF Health Heart Institute. "Our research suggests that one reason could be that both SIRT1 and SIRT3 are downregulated with aging. Younger people have higher levels of these proteins needed to make mitochondrial dynamics healthier."
The study also suggests that, before surgically opening blocked coronary arteries to restore blood flow in older patients, administering a treatment to "rescue" (improve) their diminished SIRT1/ SIRT3 levels may increase tolerance to cardiac muscle reperfusion stress, thereby reducing heart attack complications and deaths, Dr. Li said. Such a cardioprotective treatment might apply a genetic approach to increase SIRT1/SIRT3 production, or an agonist (drug) to activate SIRT1/ SIRT3, he added.
If their mouse model findings translate to human hearts, Dr. Li's group wants to work with companies interested in developing and testing SIRT1/SIRT3 activators to mitigate heart attack-related reperfusion injury.
"Our ultimate goal is to identify ideal targets for the treatment of heart attack, especially in older patients," said Dr. Li, whose research is supported by grants from the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the National Institute of General Medical Sciences.
Story Source: by University of South Florida (USF Health)