December 12, 2022 Summary: Researchers have developed a new compound, dubbed FexD, that can prevent and reverse inflammation in mouse models of inflammatory bowel disease.

Source: Salk Institute

A drug developed by Salk Institute researchers acts like a master reset switch in the intestines. The compound, called FexD, has previously been found to lower cholesterol, burn fat, and ward off colorectal cancer in mice.

Now, the team reports in Proceedings of the National Academy of Sciences on December 12, 2022, that FexD can also prevent and reverse intestinal inflammation in mouse models of inflammatory bowel disease.

“The Salk-developed drug FexD provides a new way to restore balance to the digestive system and treat inflammatory diseases that are currently very difficult to manage,” says senior author and Salk Professor Ronald Evans, director of Salk’s Gene Expression Laboratory and March of Dimes Chair in Molecular and Developmental Biology.

Inflammatory bowel disease (IBD), which includes both Crohn’s disease and ulcerative colitis, is characterized by an excess of immune cells and inflammatory signaling molecules known as cytokines in the gut.

Existing treatments, which mostly work by either suppressing the entire immune system or by targeting individual cytokines, are only effective for some patients and carry a host of side effects.

For more than two decades, Evans’ lab has studied Farnesoid X receptor (FXR), a master regulator protein that senses the bile acids delivered to the digestive system to help digest food and absorb nutrients.



When FXR detects a shift in bile acids at the beginning of a meal, it prepares the body for an influx of food by flipping on and off dozens of cellular programs related to digestion, blood sugar, and fat metabolism.

In 2015, Evans and his colleagues developed a pill called fexaramine that activates FXR in the gut. The pill, they initially showed, can stop weight gain and control blood sugar in mice.

In 2019, they showed that FexD—an updated version of fexaramine—also prevented cancer-associated changes to stem cells in the gut. Their work suggested that FXR also played a role in regulating inflammation.

“Every time you eat, you’re causing small amounts of inflammation in your gut as your intestinal cells encounter new molecules. FXR makes sure inflammation stays under control during normal feeding,” says Senior Staff Scientist Michael Downes, co-corresponding author of the new paper.

In the new work, Evans’ group discovered that activating FXR can be used to ease symptoms in inflammation-driven diseases. When the researchers gave mice with IBD a daily dose of oral FexD, either before or after the onset of intestinal inflammation, the drug prevented or treated the inflammation.

This shows a woman's stomach The compound, called FexD, has previously been found to lower cholesterol, burn fat, and ward off colorectal cancer in mice. Image is in the public domain

By activating FXR, FexD reduced the infiltration of a class of highly inflammatory immune cells called innate lymphoid cells. In turn, levels of cytokines already implicated in IBD decreased to levels normally seen in healthy mice.

See also This shows a head made up of cog wheels FeaturedNeurosciencePsychologySeptember 6, 2022 How Does Nature Nurture the Brain? “When we activate FXR, we restore appropriate signaling pathways in the gut, bringing things back to a homeostatic level,” says Senior Research Scientist Annette Atkins, co-author of the study.



Since FXR acts more like a reset button than an off switch for the immune system, cytokines are not completely blocked by FexD. This means that the immune system continues functioning in a normal way after a dose of FexD.

The compound still must be optimized for use in humans and tested in clinical trials, but the researchers say their findings provide important information about the complex links between gut health and inflammation and could eventually lead to an IBD therapeutic.

“In people with IBD, our strategy could potentially be very effective at preventing flare-ups and as a long-term maintenance drug,” says first author Ting Fu, previously a postdoctoral fellow at Salk and now an assistant professor at the University of Wisconsin-Madison.

Other authors of the paper include Yuwenbin Li, Tae Gyu Oh, Fritz Cayabyab, Nanhai He, Qin Tang, Morgan Truitt, Paul Medina, Mingxiao He, Ruth T. Yu, and Ye Zheng of Salk; and Sally Coulter and Christopher Liddle of the University of Sydney.

About this IBD and inflammation research news Author: Press Office Source: Salk Institute Contact: Press Office – Salk Institute Image: The image is in the public domain

Original Research: The findings will appear in PNAS




https://neurosciencenews.com/fexd-gut-inflammation-22062/

The protein apolipoprotein E (APOE) plays a key role throughout the body. It helps to transport cholesterol and other fatty molecules, or lipids. The gene that produces APOE comes in a few different varieties. The most common is called APOE3.

he most notorious is APOE4, which has long been linked to an increased risk of dementia in Alzheimer’s disease. People who inherit one copy of the APOE4 gene have up to a fourfold greater risk of developing Alzheimer’s disease dementia. Inheriting two copies of APOE4 elevates the risk up to twelvefold. But despite years of study, scientists have little understanding of how APOE4 affects the human brain and boosts dementia risk.

arlier research by Dr. Li-Huei Tsai of the Massachusetts Institute of Technology and others found that APOE4 might raise Alzheimer’s risk by altering lipid metabolism in certain brain cells. But the underlying details of the process remained unclear.

o build on these findings, the team conducted a multi-pronged study that assessed gene activity of all major cell types in post-mortem human brain tissue from 32 men and women who had one, two, or no copies of the APOE4 gene. Results were published in Nature on November 24, 2022.

he researchers found that APOE4 affected gene expression across all measured cell types. The team then took a closer look at genes related to cholesterol and other lipids. Cholesterol-manufacturing genes were overly expressed, and cholesterol-transporting genes dysregulated, in brain cells called oligodendrocytes with the APOE4 gene. Oligodendrocytes are found in the brain and spinal cord. They make and maintain a fatty substance called myelin that surrounds and insulates long nerve fibers. The abnormalities were more extreme in oligodendrocytes with two copies of APOE4 rather than one.

o better understand how APOE4 affects oligodendrocytes, the scientists created laboratory cultures of the cells with and without the APOE4 gene. Oligodendrocytes with APOE4 tended to accumulate abnormal amounts of cholesterol within their cells, rather than using it to make healthy myelin sheaths around nerve fibers. When the scientists examined post-mortem human brains, they noted that myelin sheaths tended to be fewer and thinner in brains that carried the APOE4 gene.

he scientists next used model systems to test whether APOE4-related abnormalities might be reversed via drugs that affect cholesterol processing. They found that a drug called cyclodextrin, which promotes cholesterol transport, reduced cholesterol buildup and improved myelin sheath formation in cultured oligodendrocytes. It did the same in mice with two copies of APOE4. The mice also performed slightly better in learning and memory tasks after treatment with the drug.

hese findings open new avenues for exploring the underlying mechanisms of Alzheimer’s disease dementia and for designing potential therapeutics.

It’s encouraging that we’ve seen a way to rescue oligodendrocyte function and myelination in lab and mouse models,” Tsai says. “I feel that lipid dysregulation could be very fundamental biology underlying a lot of the pathology we observe.”

by Vicki Contie




https://www.nih.gov/news-events/nih-research-matters/alzheimer-s-tied-cholesterol-abnormal-nerve-insulation

Fish oil still passes muster, a new study finds, but it may be time to call it quits on vitamin C, vitamin E, selenium, and beta-carotene.

ecky Upham By Becky Upham December 8, 2022 Fact-Checked

ood and bad supplements for heart health It may be time to take a second look at your daily supplements. Your heart and your wallet will thank you. Elena Brovko/iStock; Getty Images; Everyday Health Some supplements are better than others when it comes to lowering the risk of heart disease, according to a new meta-analysis published in the Journal of the American College of Cardiology.

sing data from 884 studies and more than 883,000 patients, researchers at Brown University systematically reviewed all of the existing evidence on micronutrients taken as dietary supplements. After evaluating 27 different types, they identified several that reduced the risk of cardiovascular problems like heart attack or stroke, as well as others that offered no benefit or even had a negative effect.

his analysis represents the first comprehensive, evidence-based map quantifying micronutrient supplements’ potential effects on heart health outcomes, said principal investigator Simin Liu, MD, MPH, professor of epidemiology and medicine at Brown University, in a press release. “Our study highlights the importance of micronutrient diversity and the balance of health benefits and risks,” he said.

mega-3 Fatty Acids, Folic Acid, and CoQ10 Had Strongest Evidence of Heart Benefits The randomized controlled intervention trials included in the research found the strongest evidence of heart benefits in the following supplements:

mega-3 fatty acids (fish oil), which decreased mortality from cardiovascular disease Folic acid, which lowered stroke risk Coenzyme Q10, marketed as CoQ10, which decreased all-cause mortality (death) Other supplements showing evidence of reducing cardiovascular risk were omega-6 fatty acid, L-arginine, L-citrulline, vitamin D, magnesium, zinc, alpha-lipoic acid, melatonin, catechin, curcumin, flavanol, genistein, and quercetin.

seless and Potentially Harmful Supplements for Heart Health The research found that some supplements weren’t associated with heart benefits. Vitamin C, vitamin E, and selenium showed no effect on long-term cardiovascular disease outcomes (or type 2 diabetes risk).

ne particularly concerning finding: Beta-carotene supplements were associated with an increase in all-cause mortality.

he study authors called for large, high-quality interventional trials to investigate the long-term effects of certain micronutrients.

Identifying the optimal mixture of micronutrients is important, as not all are beneficial, and some may even have harmful effects,” said Liu.

ELATED: Dietary Supplements Don’t Lower ‘Bad’ Cholesterol, Study Finds

ntioxidant Supplements Are Not Equivalent to Antioxidant-Rich Foods Antioxidant supplements are thought to play a role in heart health because these nutrients work to reduce so-called “oxidative stress,” a known contributor to many types of cardiovascular disease. Programs like the Mediterranean diet and Dietary Approaches to Stop Hypertension, which feature foods that are naturally rich in antioxidants, are both compatible with the most recent American Heart Association dietary recommendations.

ut the nutrients in supplements aren’t exactly the same as those in foods, and the results from previous studies looking at the benefits of antioxidant supplements have been inconsistent — one reason why supplements haven’t been widely adopted in preventive cardiology, according to the authors.

reviously, research on micronutrient supplementation has mainly focused on the health effects of a single vitamin or mineral or a few at a time, said Dr. Liu. “We decided to take a comprehensive and systematic approach to evaluate all the publicly available and accessible studies reporting all micronutrients, including phytochemicals and antioxidant supplements and their effects on cardiovascular risk factors as well as multiple cardiovascular diseases.”

nterested in Taking Supplements? Check with Your Doctor First “It’s a good idea to check in with your doctor before taking supplements,” says Elizabeth Bradley, MD, medical director of Cleveland Clinic’s Center for Functional Medicine in Ohio, who was not involved in this research.

f your doctor recommends an omega-3 fish oil supplement, be aware that different brands can vary in quality, says Dr. Bradley. Your provider may have suggestions about what to look for in labeling. Or you can research different brands at independent websites such as ConsumerLab.com, which reviews and rates supplements.




https://www.everydayhealth.com/heart-health/best-and-worst-supplements-for-heart-health/

A new study looked at infant mortality and found stark racial and ethnic inequities even in wealthy nations like the U.S., Canada, and the UK. Study authors call the issue ‘systemic.’

Lisa Rapaport By Lisa Rapaport December 14, 2022 Fact-Checked

Black-Infants-Have-Doubled-Mortality-Rates Black women are twice as likely as white women to receive no prenatal care, increasing the risk of complications for both mothers and newborns. iStock In many of the world’s most affluent countries, Black women are twice as likely as white women to have their babies die within four weeks of delivery, according to a new study that highlights persistent racial disparities in neonatal outcomes.

The new analysis, published December 10 in the Lancet, examined data on almost 2.2 million pregnancies across 20 high-income and middle-income countries including the United States, Canada, the United Kingdom, and several other European nations. Even after researchers accounted for a wide range of factors that can influence the risk of pregnancy and birth complications — such as age, previous pregnancies, obesity, and education levels — Black women and their infants still fared much worse.

Compared with white women, the study showed, Black mothers were more than twice as likely to have stillborn infants. Black women were also 65 percent more likely to have preterm deliveries and 39 percent more likely to have infants born small for their gestational age.

Poor Outcomes Are More Likely for Hispanic and Asian Mothers and Infants, Too Some of these outcomes were also more common for women from other racial and ethnic groups than for white mothers. For example, Hispanic women had more than three times the risk of infant death within four weeks of delivery. People of South Asian and East Asian descent were 61 percent more likely to have newborns who were small for their gestational age.

“Our analysis shows that babies of mothers from underserved and underrepresented racial and ethnic groups are more likely to die or face serious complications [and it's] a global phenomenon,” says the senior study author, Shakila Thangaratinam, MD, PhD, the chair of maternal and perinatal health at the University of Birmingham in the England.

“Race and ethnic disparities in perinatal care is not located to one specific country or region, which means that there is a systemic issue across richer countries that needs to be addressed as an international community,” Dr. Thangaratinam adds.

One limitation of the study is that many of the smaller studies included in the analysis used different definitions for certain racial and ethnic groups, making it harder to estimate outcomes for certain women of color, the study team noted. Another drawback is that researchers lacked data on insurance status and access to healthcare, making it difficult to determine whether the availability of prenatal care or other medical services influenced the outcomes.

Even so, the findings add to a large and growing body of evidence that shows how decades of declining newborn mortality rates mask stark racial and ethnic disparities in outcomes.

Black Mothers and Babies and Other Minorities Are Not Getting the Healthcare They Need While the study didn’t examine the reasons behind these disparities, other studies suggest that a complex mix of factors may be in play.

In the United States, for example, previous research has shown that Black women have infant mortality rates more than double those of white women. Black infants are also more likely to die as a result of complications related to low birth weight, and from sudden infant death syndrome, according to the U.S. Department of Health and Human Services.

Black women are also twice as likely to receive no prenatal care at all, or none until very late in pregnancy when it’s too late for doctors to prevent some complications. Early prenatal care is one of the best ways to help minimize the risk of neonatal mortality, according to the U.S. Centers for Disease Control and Prevention.

“Taken together with strong evidence that ethnic minority mothers themselves are at increased risk of death or major health complications during pregnancy, this paper further supports the need to urgently understand how healthcare systems are struggling to provide the right care for underserved families.” Thangaratinam says.




https://www.everydayhealth.com/pregnancy/black-newborns-twice-as-likely-to-die-as-white-infants-even-in-rich-countries/?slot=2&eh_uid=86162201

December 15, 2022, by Edward Winstead

An illustration of brentuximab's mechanism of action. Brentuximab vedotin binds to CD30 on the cell surface and is then taken inside the cell. Once there, the drug MMAE is released and prevents the cancer cell from dividing.

Credit: Adapted from Journal of Hematology & Oncology. April 2018. https://doi.org/10.1186/s13045-018-0601-9. CC BY 4.0. The Food and Drug Administration (FDA) has approved the drug brentuximab vedotin (Adcetris) in combination with chemotherapy for the treatment of some children and adolescents with Hodgkin lymphoma.

The approval, announced on November 10, covers use of the combination as an initial treatment for people 2 to 21 years of age with high-risk classical Hodgkin lymphoma.

In 2018, FDA approved brentuximab vedotin as an initial, or first-line, treatment for adults with advanced Hodgkin lymphoma.

The approval in younger people was based on an NCI-sponsored clinical trial conducted by the Children’s Oncology Group. In the trial, approximately half of the participants were randomly assigned to receive brentuximab vedotin and a chemotherapy-based regimen consisting of doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide.

The other patients received the same chemotherapy-based regimen along with bleomycin, which was a standard of care for children and adolescents with high-risk classical Hodgkin lymphoma.

In the study, brentuximab vedotin plus chemotherapy was superior to standard-care chemotherapy based on a measure known as event-free survival. In the trial, event-free survival was the length of time from when a patient was randomly assigned to a treatment group until disease progression or relapse, second cancer, or death due to any cause.

At a median follow-up of 42 months, 92.1% of those in the brentuximab vedotin group had not experienced an event compared with 82.5% of those in the standard-care chemotherapy group, according to findings published November 3 in the New England Journal of Medicine (NEJM).

“These results describe an important advance,” said Malcolm Smith, M.D., Ph.D., of NCI’s Cancer Therapy Evaluation Program.

“The improvement in event-free survival is clinically meaningful and establishes the role of brentuximab vedotin as an important agent for successfully treating Hodgkin lymphoma in this patient population,” Dr. Smith added.

A targeted drug for kids with Hodgkin lymphoma In people with classical Hodgkin lymphoma, cancer cells form in the lymph system. Although this type of lymphoma is uncommon in the general population, it is one of the most commonly diagnosed cancers in adolescents aged 15–19.

Brentuximab vedotin, which is given by intravenous injection, is a type of targeted therapy called an antibody-drug conjugate. The antibody part of the drug recognizes a protein called CD30, which is often found at high levels on Hodgkin lymphoma cells called Reed-Sternberg cells. When the antibody binds to CD30 on these cancer cells, it delivers the drug vedotin to the cell, which interferes with cell division and leads to the cell’s death.

To conduct the trial, Sharon Castellino, M.D., MSc, of Winship Cancer Institute of Emory University and Children’s Healthcare of Atlanta and her colleagues in the Children’s Oncology Group enrolled 600 children and adolescents with stage IIB with bulk tumor, or stage IIIB, IVA, or IVB Hodgkin lymphoma.

“The study enrolled a significant percentage of patients from minority populations that are [usually] underrepresented in clinical trials, which is extremely important,” said Ann S. LaCasce, M.D., a lymphoma specialist at the Dana-Farber Cancer Institute who was not involved in the research. “This has not been the case in adult studies, and the Children’s Oncology Group should be applauded for their efforts.”

In the pediatric trial, brentuximab vedotin plus chemotherapy “resulted in the best outcomes we have ever seen in patients with Hodgkin lymphoma and high-risk disease,” Dr. LaCasce added.

Longer follow-up is needed to determine for each group whether there are late relapses of Hodgkin lymphoma or development of second cancers.

Reducing the amount of radiation used to treat young patients More than half of the participants in both groups received radiation therapy after completion of chemotherapy for tumors that, based on PET imaging performed part way through their treatments, were slow to respond, or shrink.

The radiation was tailored for individual patients and involved smaller areas and lower doses than have been used in previous pediatric trials, noted Dr. Castellino.

For Kids with Hodgkin Lymphoma, Less Radiation a Possibility In a new trial, a treatment regimen using brentuximab was effective and minimized the need for radiation.

“In general, we are all trying to limit the use of radiation given the risk of long-term side effects,” said Dr. LaCasce. “Recent studies have demonstrated that we can significantly reduce the use of radiation by using PET scans to measure early responses to treatment.”

As the authors of an accompanying editorial in NEJM wrote, “Limiting the radiation dose, reducing exposure to normal tissue, and omitting radiation therapy altogether remain important goals.”

Adding brentuximab vedotin to the chemotherapy-based regimen did not increase side effects, the researchers found. A side effect that has been reported in adult trials involving brentuximab vedotin—severe peripheral neuropathy, which can cause pain and tingling in parts of the body—was less common in the Children’s Oncology Group trial, noted Dr. Castellino.

The most common side effects in the brentuximab vedotin group included low white and blood cell counts, inflammation or irritation in the mucous membranes in the mouth (stomatitis), and infection.

During the treatment phase of the clinical trial, less than 10% of patients who received brentuximab vedotin needed a dose reduction because of side effects, according to Kara Kelly, M.D., of Roswell Park Comprehensive Cancer Center and University of Buffalo School of Medicine and Biomedical Science and a leader of the trial.

“The FDA approval is a win for children” The findings from the Children’s Oncology Group trial are consistent with the results of a smaller study published last year. In that study, which did not include a control group, brentuximab vedotin plus chemotherapy showed promise as an initial treatment for children and adolescents with high-risk Hodgkin lymphoma.

But experts agreed that those study results were not conclusive. “The new [Children’s Oncology Group] findings provide definitive evidence that brentuximab vedotin can improve outcomes for children with high-risk Hodgkin lymphoma,” said Dr. Smith.

Dr. Castellino agreed. “The FDA approval is a win for children who now have access to a targeted therapy for Hodgkin lymphoma for the first time.”




https://www.cancer.gov/news-events/cancer-currents-blog/2022/fda-brentuximab-children-hodgkin-lymphoma?cid=eb_govdel

Can resetting brain circuits help people find recovery?

Home News & Events Research Spotlights Deep Brain Stimulation for Severe Opioid Addiction ImageDeep brain stimulation delivers a mild electrical current through a thin wire to alter brain activity in the brain’s reward center (see red plus sign) Deep brain stimulation delivers a mild electrical current through a thin wire to alter brain activity in the brain’s reward center (see red plus sign).

Image credit: WVU Rockefeller Neuroscience Institute

Repeated drug use changes the brain, which is one reason addiction is so hard to overcome. Over a period of weeks to months, use of opioids and other substances alter brain circuits as the body adapts to the effects of these chemicals.

Yet, with repeated drug use over time, the body may need more and more drug to feel the same effect. People with drug addiction often continue to use drugs to avoid the harrowing physical and psychological withdrawal symptoms from stopping drugs abruptly – creating a vicious cycle that is hard to break.

The Helping to End Addiction Long-term® Initiative, or NIH HEAL Initiative® recognizes that multiple strategies are needed to address all aspects of the addiction lifecycle. That means identifying risk factors, stopping overdoses, developing effective treatments, and promoting stable recovery. For each of these aspects, technology can be a powerful tool.

In a particularly innovative approach, HEAL-funded neurosurgeon Ali Rezai, M.D., of the West Virginia University Rockefeller Neuroscience Institute in Morgantown is evaluating the use of deep brain stimulation for patients with severe, treatment-resistant opioid use disorder.

Resetting the Brain The human brain is a complex and dynamic labyrinth of interconnecting circuits. It allows us to sense the world around us as well as respond to changing conditions. In turn, the brain adapts.

“An individual is not destined to be a person with addiction, but with continued drug use they become that person over time,” Rezai explains. The brain gets “rewired” to create changes in the brain’s reward circuit deep in the brain where dopamine is released in response to rewarding stimuli like drugs.

With repeated drug use, however, dopamine production drops off, and craving intensifies. More and more drug is needed to produce a high. The reward circuit sends signals to another part of the brain, the prefrontal cortex, which helps control behavior and is important for decision making and working toward goals.

Overstimulation of the reward center and understimulation of the behavior control center create a difficult combination: the desire and physiological need to use more drugs and less impulse control to resist. In this scenario, it is very difficult for people who try to quit drugs.

Rezai is leading a HEAL research study to help change brain circuits whose activity underlies drug addiction, using focused electrical energy from an implanted device. Called deep brain stimulation, the procedure is sort of like a pacemaker for the brain that can restore a healthy electrical activity and rhythm. Over the past 30 years, neurosurgeons like Rezai have inserted more than 200,000 deep brain stimulation implants into patients with a range of neurologic disorders.

Stimulating Hope Deep brain stimulation delivers a mild electrical current to a specific brain region to alter its activity, tuning it up or down. The technique has been used successfully to treat Parkinson’s disease, where it acts like and on-off switch for tremors characteristic of this debilitating movement disorder. Deep brain stimulation is also used to treat epilepsy and obsessive-compulsive disorder, and researchers are testing deep brain stimulation for several other conditions including chronic pain, depression, and Alzheimer’s disease.

Rezai’s HEAL research is now testing deep brain stimulation as part of a strategy for opioid use disorder that has not responded to other treatments. Rigorously designed experiments are critical for determining whether this technology, in combination with other treatments like medication and counseling, can reset the brain and lead to reduced drug use. Although some studies have been done in China and Europe, Rezai’s is the first to be designed, controlled, and regulated by the U.S. Food and Drug Administration to determine how well this approach works.

Participants in Rezai’s deep brain stimulation study have chronic, severe opioid use disorder. These individuals (four, so far) have experienced multiple overdoses and typically have not responded to all of the treatments they have tried: inpatient, outpatient, or sober housing approaches. Participating in this research study represents a big leap of hope for recovery.

Determining if the approach is safe is the current goal. In the coming months, 20 more patients will receive an implant toward bringing their brain back into balance. If deep brain stimulation proves to be effective for stabilizing their brain rhythms as planned, the approach might offer a life-changing opportunity for people who have exhausted other options.

Hitting the Target ImageThe brain wire (left) is connected to a pacemaker in the chest (right) that can both stimulate and record electrical activity. The deep brain stimulation wire (left) is connected to a pacemaker in the chest (right) that can both stimulate and record electrical activity.

Image credit: WVU Rockefeller Neuroscience Institute

Although the human brain is only about 3 pounds, it is packed with 86 billion neurons and billions of other cells, including those that make up blood vessels – all encased in a protective bone structure. Finding the precise spot to target with a stimulating contact and electrode is tricky.

This deep brain stimulation procedure takes about 6 hours, during which Rezai threads a tiny 1 mm-diameter brain lead with four electrode contacts through a nickel-sized hole in the skull and down to brain structures that are part of the reward circuit. The brain wire is connected to a pacemaker in the chest that can both stimulate and record electrical activity. Only the research team can tune up or down electrical stimulation of brain within study participants.

Magnetic resonance imaging guides neurosurgeons like Rezai to be able to see the reward structures in a participant’s brain, and a computer modeling program uses those images to create a 3D map of the brain circuit. Because those patterns are highly unique among brain regions, they can be used to distinguish circuits right next to each other that perform completely different functions. Thus, the implant can be placed precisely where it needs to go.

Perhaps the most important help, though, comes from the person on the operating table, who is awake and can respond to cues (like being shown a picture of drug injection). The research team measures reactions to these cues that cause changes in brain activity both to guide placement of the implant and to calibrate the device for each patient. Because the brain and skull are not able to sense pain, and the scalp has been numbed in advance, the procedure does not hurt.

Throughout the study, Rezai and his research team offer 24/7 support to all participants and can tweak stimulation as needed. For example, one individual called over a weekend and was struggling with severe anxiety. When the researchers took another look at their brain imaging maps and the location of the implant, they knew why: too much stimulation to a nearby brain region linked to fear and emotions.

“So we moved the stimulation higher up,” Rezai explains, to get closer to the prefrontal cortex, “and his symptoms dramatically improved.”

Beyond Surgery In the search for lasting treatments for opioid addiction, a person-centric focus is necessary to accommodate individuals on their personal road to recovery. Most people need a range of strategies, including medications, counseling, and other support services. All of these are continued after an implant is placed within an individual’s brain to deliver stimulation treatment.

Another important goal of this research is to better understand how reward and behavior pathways change with craving, relapse, and recovery. Rezai and his team are looking for electrical signatures of brain changes that affect behavior: “We’re working on ways to continuously monitor addiction pathways in the brain wirelessly.”

As a first step to finding such signatures, the scientists use the implanted electrodes to measure electrical activity in the brains of people participating in the study. In time, as these paths become clearer, deep brain technology could be able to automatically sense and deliver therapy to optimize electrical signals and restore healthy rhythms.

Although the main goal of this research study is to determine safety, the team is cautiously optimistic from early results and thrilled for the improved health of the small group of participants who have undergone the procedure.

“Our first patient celebrated sobriety and complete abstinence for 3 years. He used to relapse every other week,” Rezai says, adding that another has been entirely abstinent for more than a year and is now working as a peer recovery coach.

“They go from severe, end-stage addiction to becoming therapists themselves … that’s really amazing.”




https://heal.nih.gov/news/stories/deep-brain-stimulation?utm_source=ownedeblast&utm_medium=email&utm_campaign=digest-dec2022

December 9, 2022, by Linda Wang

diagram of the signaling pathway in cells blocked by ganitumab and trametinib. Ganitumab and trametinib (Mekinist) block the activity of different molecular targets, IGF-1R and MEK, in the same communication pathway in cancer cells.

redit: National Cancer Institute/Marielle Yohe, M.D., Ph.D. An NCI study in mice has identified a potential new treatment for children with rhabdomyosarcoma, a type of cancer that affects the muscles and other soft tissues.

he treatment—an experimental drug, ganitumab, in combination with the targeted drug trametinib (Mekinist)—stopped rhabdomyosarcoma tumors from growing and even shrank some tumors in the treated mice.

he findings were published November 2 in Clinical Cancer Research.

ased on these promising results, the researchers want to test this combination in humans in a phase 1 clinical trial. But the company that makes ganitumab discontinued the drug after it failed to work in adult cancers, and any remaining supply of the drug has expired.

This type of roadblock is frustrating,” said Marielle Yohe, M.D., Ph.D., of NCI’s Center for Cancer Research, who led the study. “We've identified this combination of drugs that would make a great clinical trial but, unfortunately, we find ourselves in a position where we don't have access to [ganitumab].”

r. Yohe and her co-investigators are now exploring options for obtaining a drug similar to ganitumab so they can continue their studies. Even so, the team’s experience is all too common in childhood cancer research, said Douglas Hawkins, M.D., of Seattle Children’s Hospital and group chair of the NCI-funded Children’s Oncology Group.

Every year, there are a couple of drugs that are put on the shelf that we would have been interested in continuing development of, but because the adult study failed, there's no path to move forward,” Dr. Hawkins said. “If you're a drug company, developing a drug for a pediatric indication may not make financial sense because pediatric cancers are so rare. And that's the harsh reality.”

opeful results in mice Rhabdomyosarcoma accounts for about 3% of all childhood cancers. The disease is usually curable if it is treated before it has spread. But if the cancer returns after treatment or spreads to other areas of the body, it is extremely difficult to treat. However, targeted drugs, particularly in combination, may offer some hope of improving these outcomes, Dr. Yohe said.

n 2018, Dr. Yohe and her colleagues showed that the combination of trametinib and a drug called BMS-754807 slowed tumor growth in mouse models of rhabdomyosarcoma. Trametinib blocks the activity of a protein in cancer cells called MEK that fuels tumor growth, and BMS-754807 blocks IGF-1R, another protein involved in tumor growth. However, the combination caused severe side effects in the mice, including excessive weight loss.

anitumab is a monoclonal antibody that also blocks the activity of IGF-1R but, based on findings from a small clinical trial, may have fewer side effects. The researchers wondered whether combining trametinib with ganitumab would shrink tumors and cause fewer side effects than the trametinib–BMS-754807 combination.

n illustration with two panels. On the left, PAX3-FOXO1 interacts with KDM4B in front of stretched-out DNA. On the right, KDM4B is crossed out and the DNA is wound up. A Potential Treatment for Rhabdomyosarcoma Shows Promise In mice, a drug that blocks the KDM4B enzyme eliminated tumors driven by a fusion protein.

n the new study, the researchers found that the combination of trametinib and ganitumab shrank tumors in several mouse models that closely resemble the most common type of rhabdomyosarcoma.

n several of the models they studied, mice given the combination treatment lived substantially longer than mice that did not receive the drugs or received just one of the drugs. Even after the researchers stopped treatment for a period of time, in some of the mice, the tumors didn’t grow back. The combination therapy also appeared to have few side effects.

r. Yohe said this is one of the first combinations of targeted therapies for advanced rhabdomyosarcoma that shrinks tumors in animal models. Drugs such as trametinib and ganitumab typically cause a delay in tumor growth, not tumor shrinkage.

anitumab gets discontinued During the study, however, ImmunityBio, the company that had been making ganitumab, stopped producing the drug. That move came on the heels of disappointing results with the drug in clinical trials of adult cancers, such as pancreatic and lung cancer.

ther studies of ganitumab have also been affected as a result. For example, an NCI-led phase 2 trial testing the combination of ganitumab and dasatinib (Sprycel) for rhabdomyosarcoma had to be stopped early when ganitumab became unavailableExit Disclaimer.

Because of drug availability issues like this, it's been quite difficult to start new trials, and the direct patient consequence is that we're not moving the survival bar,” Dr. Yohe said. “In the last 20 or 30 years, we haven’t been able to improve survival in the advanced form of this disease.”

r. Hawkins pointed out that many other IGF-1R antibodies have also failed to show effectiveness in adult cancers.

Drug development has been abandoned for this class of drugs,” he said. “They were not abandoned because of lack of activity in childhood cancers, they were abandoned because of lack of activity in common adult cancers.”

ut pediatric cancers are genetically different from adult cancers, he said, and some drugs that don’t work in adult cancers could potentially be very effective in pediatric cancers, particularly in combinations. For example, overactivity in the communication pathway in cells in which IGF-1R plays a central role is far more common in childhood cancers than in adult cancers, he noted.

aved Khan, M.D., a co-investigator on the new study with Dr. Yohe, said that when they are planning a research study, they try to use drugs that have shown effectiveness in adult cancers in the hope of avoiding drug access issues like the one they are facing with ganitumab.

ut, Dr. Khan added, it’s not possible to predict how drug development will play out. When they started their research, IGF-1R looked like it would be a good target for adult cancers, he said.

idespread frustration over discontinued drugs Drs. Yohe and Khan are not alone in their frustration.

This problem is rampant, and it's happening all the time in different forms,” said Emily Slotkin, M.D., of Memorial Sloan Kettering Cancer Center, who has experienced a somewhat similar hurdle in her research for an effective treatment for desmoplastic small round cell tumor, a rare and aggressive type of sarcoma that is most common in young people. It involves a drug now called ACR-368.

child with cancer and his mother talking with family via a tablet computer. Progress against Childhood Cancer with Better Data, Clinical Trials Dr. Doug Hawkins, chair of the Children’s Oncology Group, discusses efforts to improve the lives of kids with cancer.

In a small clinical trial led by Dr. Slotkin, the combination of ACR-368 and the chemotherapy drug irinotecan shrank tumors in some patientsExit Disclaimer, and the researchers want to study the combination further. Although Eli Lilly initially developed ACR-368 (then known as prexasertib), the company discontinued the drug’s development in 2019. Acrivon Therapeutics later licensed the compound from Eli Lilly.

With the licensing of ACR-368 by Acrivon Therapeutics, we are hopeful that we will still have the chance to gain access to this compound in the future,” Dr. Slotkin said.

verall, she continued, issues limiting access to potentially promising drugs are affecting the pipeline of new pediatric cancer treatments and the pipeline of researchers interested in studying new drugs for pediatric cancers.

These types of barriers contribute to the sense of futility that researchers feel when they're trying to get their ideas to fruition,” she said. “The more barriers they face, the less enthusiastic they are to do the work that could potentially help a patient. It affects everybody's morale.”

emoving drug development roadblocks for childhood cancers To help incentivize drug development for childhood cancers, the Food and Drug Administration has a priority review voucher program that rewards companies for developing drugs to treat children with rare and life-threatening diseases.

ut that may not be enough of an incentive for a company to take a chance on a drug that, even if effective, will be used by a relatively small number of patients, Dr. Hawkins said.

CI has, in the past, stepped in temporarily to continue the development of a drug that did not have a commercial sponsor. Such was the case with the neuroblastoma treatment dinutuximab (Unituxin), which was initially manufactured by NCI until it found a company to take over continued development and manufacturing. Dr. Khan said he and Dr. Yohe are looking into this option.

ut “it’s a steep uphill climb,” he continued, and this type of partnership happens rarely. Another potential path forward is for researchers to partner with drug companies whose philosophy is to develop drugs for children, but these companies tend to be very small and have limited resources.

more realistic option for researchers is to find other drugs to test. But that’s not ideal either.

To restart work with another agent is expensive and inefficient, but is sometimes the other viable path forward,” Dr. Slotkin said. “However, the more you start over and over again, the slower you go.”

here’s also no guarantee that another drug won’t face the same access issue. “You want to have many irons in the fire, but there may not even be that many irons to pursue,” she said.

s for the rhabdomyosarcoma study, Dr. Khan said they are not ready to give up on ganitumab yet and are continuing to explore different options. “These are good results and could be a potential treatment for patients,” he said.

r. Slotkin is also staying hopeful. “At the moment, the way forward is patience and diligence,” she said. “We’ll keep chipping away at this until we can get the study done.”




https://www.cancer.gov/news-events/cancer-currents-blog/2022/rhabdomyosarcoma-trametinib-ganitumab-shrinks-tumors?cid=eb_govdel

Two randomized, placebo-controlled trials evaluating three Ebola vaccine administration strategies in adults and children found that all the regimens were safe in both age groups, according to results published today in the New England Journal of Medicine. Antibodies were produced in response to the vaccine regimens beginning at 14 days after the first vaccination and continued to be detectable at varying levels—depending on the vaccine and regimen used—in both children and adults for one year. The study enrolled volunteers at sites in Guinea, Liberia, Sierra Leone and Mali to identify optimal vaccination strategies to curtail outbreaks of Ebola virus disease.

The trials were conducted under the Partnership for Research on Ebola Vaccination (PREVAC) international consortium. PREVAC’s partner organizations include the U.S. National Institutes of Health (NIH), the French National Institute of Health and Medical Research and the London School of Hygiene & Tropical Medicine. The National Institute of Allergy and Infectious Diseases (NIAID), part of NIH, sponsored the trial in Liberia and Mali. In Liberia, the study was done in collaboration with the Liberia Ministry of Health through the Partnership for Research on Ebola Virus in Liberia program. In Mali, it was conducted in collaboration with the University Clinical Research Center and the Center for Vaccine Development-Mali.

The trials began enrollment in 2017, were conducted simultaneously and shared a placebo arm. A total of 1,400 adults and 1,401 children aged 1 year to 17 years old were randomized to receive two injections of either placebo or Ebola vaccine in one of three regimens. The Ebola vaccine regimens were Ad26.ZEBOV (supplied by Johnson & Johnson) followed eight weeks later with a booster dose of MVA-BN-Filo vaccine (supplied by manufacturer Bavarian Nordic); two doses of rVSVG-ZEBOV-GP (manufactured by Merck Sharp & Dohme Corp) separated by eight weeks; or one dose of the Merck vaccine followed eight weeks later by a placebo injection.

Antibody responses were observed by day 14 after the first injection of either Ad26.ZEBOV or rVSVG-ZEBOV-GP vaccine. The researchers say this finding is notable because vaccines against Ebola virus disease are typically administered during an outbreak and so information about how rapidly a vaccine produces an antibody effect is of potential use in efforts to protect at-risk populations. However, it is not currently known what level of antibody response reliably correlates with vaccine-induced protection against Ebola virus infection or disease. As no participants contracted Ebola virus disease during the trial, the investigators were not able to assess protection from disease.

The researchers cite several strengths of the trials, including outstanding retention of volunteers throughout the course of trial, achieved with continuing community engagement and ongoing trust-building efforts.




https://www.nih.gov/news-events/news-releases/ebola-vaccine-regimens-safe-immunogenic-adults-children

nk you Accept Why You Can Trust CNET Our expert, award-winning staff selects the products we cover and rigorously researches and tests our top picks. If you buy through our links, we may get a commission. Reviews ethics statement Wellness Mental Health Enhance Your Mental Health With These 6 Daily Thought Exercises In times of stress, thought exercises can help you get through.

Laura Leavitt headshot Laura Leavitt Dec. 15, 2022 11:00 a.m. PT 7 min read Dumbells and model brain You don't have to let stress or negative thinking take over your life. RapidEye/Getty Images Health Tips logo When we're stressed, it's easy to get stuck in a cycle of negative thinking can we can't seem to kick. If you've been stuck in a rut with your mental health, you're probably looking for anything to help you out.

Thought exercises are a simple and no-cost way to kick negative thinking. They are designed to help you perceive things in a new light and put you back in control.

They can also help us make our subconscious thoughts go in more productive, helpful directions over time, and they'll eventually cut out those negative thinking patterns entirely. We pulled together a list of the top six thought exercises that improve mental health, and we'll show you how to perform them.

Also learn which foods to eat for a happiness boost and which color to paint your bedroom for the best mental health.

Best Mental Health Apps for 2022 See at Cnet

What is a thought exercise? Thought exercises are new ways to think about a given circumstance or experience that can help us get out of a stuck or unhelpful way of thinking. While some thought exercises have been studied extensively by psychological researchers, others are offered by psychologists and clinical mental health counselors because they've been helpful anecdotally for specific types of patients. Thought exercises may be suggested by your therapist, whether they are online or in-person.

Read more: 5 Best Online Therapy Services

It's important to keep in mind that there isn't a one-size-fits-all thought exercise. Feel free to try one of them for a few weeks and see if you like the way they impact your mental health and feelings of well-being. If not, you can try a different one. Thought exercises are meant to be a method of seeing the world differently, not a medical treatment.

What are the benefits of thought exercises for mental health? Reframing thoughts is one of the building blocks of cognitive behavioral therapy, which has been found effective in many studies.

A go-to thought exercise can help one maintain calm during a stressful moment and continue functioning, staving off a more severe reaction like an anxiety attack. Thought exercises can reduce the duration and intensity of anxiety symptoms even when not combined with traditional therapy. When paired with a mental health app, thought exercises can provide a log of one's growth and changes in mental health. Thought exercises can make us more mindful of what triggers our anxiety, allowing us to make life modifications that help us to experience anxiety less often. Read more: What to Know About Anxiety, Symptoms and Treatment

6 thought exercises that will boost your mental health Next time you're feeling stressed out, try one of these methods to help combat overwhelming feelings.

The self-observation exercise Many spiritual traditions include some kind of self-observation or mindfulness exercise, but it is helpful in a completely nonspiritual context as well. When you begin to experience the symptoms you associate with anxiety, you can use this exercise to get curious and learn more about what you're going through. Here's how to do it:

1. When you're feeling anxious and have the opportunity to take a couple minutes to yourself, do so. Get away from others so you won't be interrupted, even if it's just a few minutes.

2. Start noting the way that every element of your body feels. Are you feeling the anxiety in your shoulders, neck, stomach or head? Are you experiencing other symptoms, like fatigue or a headache? Don't judge the feelings, just note them, like you were observing a scientific experiment and needed to catch everything.

3. Then turn your self-observation to your thoughts. What are the specific stressors cycling through your mind? Try to catalog them, rather than letting them overwhelm you. When you've noticed one, let it go, recognizing that you've heard it.

4. If you can get to a place of fully focusing on bodily and mental sensations, you may find yourself able to calm down, doing things like releasing the muscles you've discovered are tense or letting thoughts go instead of holding onto them intensely. This may take a few tries.

The act of self-observation can be a way to take your mind off the anxiety and come back to your body. When we're in fight-or-flight mode, the anxiety gets us to safety, but if we are physically safe, this can be a way to evaluate our body and find our baseline again.

low angle view of woman in yoga prayer pose Self-observation exercises can help you stay grounded in the present.

Thomas Barwick/Getty Images Keep a thought record One of the ways that people better understand their anxiety symptoms is by recording their thoughts. This can be done in a traditional paper journal, but there are other options, especially when it's inconvenient to carry an extra notebook everywhere. The app Thought Diary is a simple interface, letting you write down your mood and any details about it. It also includes other thought exercises, such as practicing gratitude and analyzing a thought.

Reviewing your thought record occasionally can help you draw connections, including things like how sleep, exercise and nutrition impact your anxiety symptoms.

Interrupt anxious thinking Anxious thinking responds best to being distracted by a different task. These techniques are more about what effectively distracts you and less about a technically right method.

Try tensing and relaxing different muscles in your body, focusing on the muscle activity and seeing if it can help you stop thinking anxious thoughts. Breathing with an intentional count, like four counts in and four counts out. Putting on music, an audiobook or a radio show can interrupt anxious thoughts and bring your mind to bear on something else. Loudly saying that you're done thinking this way or verbally speaking affirmations can help get out of one's head and hear a positive voice more clearly. Choosing a soothing task that is also mentally engaging: word games on your phone, loading a dishwasher, doing a yoga flow or other set routine of stretching can all be effective anxiety interruptions. Counting backward slowly sometimes works to interrupt the flow of anxiety. Read more: 8 Science-Backed Exercises to Relieve Stress

Use cognitive defusion exercises Cognitive defusion exercises are all about getting an outside perspective on our thoughts, or strategies that help us detach and look more clearly at our thoughts. They are used frequently in CBT and other types of cognitive therapy.

Use a silly voice: Some people find it helpful to detach from their thoughts by using a silly voice to say something like, Oh, you think this is very concerning, do you? or some other observation about the thought. Leaves on a stream: Some people use the visualization that their thoughts are floating down a river, coming to them and then going away, as a way to see the thoughts as separate from their core identity. Label your thoughts: Some people find it helpful to identify that is an anxious thought or this is a fearful thought as they have the thoughts, helping to take them out of being an assessment of reality and treating them as separate items which don't have to be believed outright. Thank you mind: When our minds tell us a warning in the form of an anxious thought, we can offer gratitude to our mind for trying to help us and warn us. Practice self-compassion Anxiety sometimes presents as excessive worry that one isn't good enough or has negative traits. These thoughts, when played on a loop, can be demoralizing and can make everyday activities miserable. A way to combat this negative self-talk is to practice self-compassion. While it may seem odd at first, trying to see your current situation the way you'd see it if a good friend was going through it can be a start. Give yourself the kind of comfort you'd give a friend, instead of the harsh critique you often give yourself.

Another self-compassion exercise is to find and focus on a photograph of yourself from childhood. Instead of directing your thoughts toward your adult self, direct them to that child. Recognize that your adult self deserves the same kind of comfort that a child deserves, as you are also still learning, albeit different things.

The worry tree The worry tree is a tool developed for those who experience compulsive or continual worry to help them make a conscious decision between worrying or doing something else. It is a flowchart graphic that is customizable to the person, but essentially starts by questioning, what exactly am I worried about? then Can I do something about it? and Can I do something about it right now? The tree guides people to let worries go when nothing can be done, to make a clear plan if nothing can be done right now, and to go do something if there is something useful to be done about the worry right now. It can help avoid rumination, where we think the same anxiety-inducing thoughts over and over without relief.

Read more: 9 Ways to Relieve Anxiety Without Medication

The bottom line Thought exercises can feel different from our typical ways of thinking, but if you remain curious, you may find your mind changing, experiencing more methods for how to think positively over time. If you find that thought exercises make your anxious symptoms worse, you may have an ineffective thought exercise for yourself, or your anxiety might respond better to treatment from a psychiatrist or counselor. Talking with a mental health professional is a good idea to get better answers about your specific situation.

More mental health advice 8 Anxiety Myths You Can Stop Believing Today 3 Reasons You Should Use a Weighted Stuffed Animal for Anxiety 7 Ways to Support a Partner With Anxiety Naturally Produce More Dopamine, Serotonin, Endorphin and Oxytocin for a Happier Brain Try Light Therapy to Manage Seasonal Affective Disorder Symptoms First published on Oct. 5, 2022 at 7:00 a.m. PT.

The information contained in this article is for educational and informational purposes only and is not intended as health or medical advice. Always consult a physician or other qualified health provider regarding any questions you may have about a medical condition or health objectives.




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Reviewed by Emily Henderson, B.Sc.Dec 14 2022 Researchers have characterized prostate cancer cell dynamics at a single-cell resolution across the timespan of the disease – from its beginning to the point of androgen independence, where the tumour no longer responds to hormone deprivation therapy.

Their study in mice, published today in eLife, reveals an expansion of intermediate cells that occurs in prostate cancer, which correlates with resistance to treatment and poor clinical outcomes in humans. These cells are castration-resistant, meaning they continue to grow in the absence of testosterone and could explain how prostate tumors become resistant to hormone-related treatments.

Prostate cancer is the most diagnosed form of cancer, and the second-leading cause of cancer-related deaths in males from the US. This is in large part due to an incomplete knowledge of the cellular drivers behind the disease's progression and the risk of progressing to castration-resistant prostate cancer (CRPC).

The prostate gland epithelium – a type of body tissue that forms the surface of glands and organs – is typically composed of two types of epithelial cells: basal cells and highly-differentiated luminal cells (cells which have altered in form). However, a more stem-like, castration-resistant intermediate of the luminal cells has previously been proposed.

It has been suggested that normal luminal cells are able to transition into these progenitor cells under castrate conditions. There is evidence that these cells contribute to the initial development of tumours in the prostate and resistance to treatment in advanced cancers, although this is yet to be confirmed in other models of CRPC.

Alexandre Germanos, lead author, PhD candidate in Molecular and Cellular Biology at the University of Washington, US, and graduate student at the Division of Human Biology, Fred Hutchinson Cancer Center, US

To study this further, Germanos and colleagues used a mouse model of CRPC to create an 'atlas of prostate cellular composition and evolution' through the course of the disease.

A gene called Pten, which codes for a tumor-suppressing enzyme, is inactive in the majority of advanced prostate cancer patients. The team used a technique called single-cell RNA sequencing to compare the epithelial and non-epithelial cell-type populations in healthy mice and those lacking Pten.

In the prostate of healthy mice, they observed multiple epithelial cell types – basal, luminal and luminal progenitor cells. In the prostate of mice lacking Pten, they observed an expansion of luminal intermediate cells, likely derived from three cellular sources – basal cells, luminal progenitor cells and differentiated luminal cells. This suggests that basal cells can transform into intermediate cells upon Pten deletion, supporting other findings in the field. The team also observed further expansion of cancerous intermediate cells upon hormone deprivation which significantly increased the diversity of cells within a tumor (known as tumor heterogeneity). They demonstrated that this heterogeneity can be constrained by inhibiting protein synthesis.

Related Stories Characterization of immune evasion and cell entry for new variants: BQ.1.1, XBB.1, and BR.2.1 Researchers identify a new target gene in pancreatic ductal adenocarcinoma Experimental therapy shows promise as treatment for metastatic colon cancer in preclinical models The team then sought to characterize the effects of this hormone deprivation-induced intermediate cell expansion. In the intermediate cells, they discovered that a 5-gene signature is specifically enriched. Using two datasets of bulk RNA-sequencing from prostate cancer patients, they showed that the signature is associated with treatment resistance and poor clinical outcomes. Furthermore, the signature is enriched in a subset of metastatic human prostate cancer cells – tumours that are able to spread – but not in the primary tumor cells.

These findings suggest that a 5-gene signature derived from mouse models of prostate cancer may have importance in understanding human disease. The presence of this gene signature may serve as a useful prognostic tool for predicting treatment resistance and outcomes in patients. The authors call for further studies to validate the role of this signature and of intermediate-like cell populations in individuals with prostate cancer.

Their analysis also revealed that the prostate in mice without Pten is highly enriched for immune cells that promote the production of tumors, creating a microenvironment that helps tumors evade suppression by the immune system. Pro-tumorigenic macrophages, a specialized cell type involved in the destruction of harmful organisms, are recruited by epithelial cells and a type of cell that contributes to forming connective tissue, called fibroblasts. This suggests that interrupting the recruitment of tumor-associated macrophages may be a valid strategy to overcome immunotherapy resistance in prostate cancer.

Overall, our work highlights multiple epithelial and immune cell types that are crucial to prostate cancer initiation and progression, and sheds light on the interactions between specific cell populations that contribute to castration-resistance, concludes senior author Andrew Hsieh, Associate Professor in the Division of Human Biology, Fred Hutchinson Cancer Center, and the Department of Medicine and Genome Sciences (affiliate), University of Washington.

We wanted to provide a broad, searchable resource for cancer researchers and encourage further research in the area. We've therefore developed a publicly accessible and interactive website that allows scientists to run cell- and gene-specific queries through all 50,780 cells analysed in our study.

Source: eLife

Journal reference: Germanos, A.A., et al. (2022) Defining cellular population dynamics at single-cell resolution during prostate cancer progression. eLife. doi.org/10.7554/eLife.79076.




https://www.news-medical.net/news/20221214/Expansion-of-intermediate-cells-in-prostate-cancer-correlates-with-treatment-resistance-and-poor-outcomes.aspx#amp_tf=From%20%251%24s&aoh=16711328618613&csi=0&referrer=https%3A%2F%2Fwww.google.com&share=https%3A%2F%2Fwww.news-medical.net%2Fnews%2F20221214%2FExpansion-of-intermediate-cells-in-prostate-cancer-correlates-with-treatment-resistance-and-poor-outcomes.aspx

By Jamie Gumbrecht, CNN Published 8:59 AM EST, Tue December 13, 2022



Video Ad Feedback Could lab-grown organs and cancer vaccines be the future of medicine? 23:08 - Source: CNN CNN — An experimental personalized mRNA vaccine in combination with the immunotherapy Keytruda reduced the risk of recurrence or death from melanoma in patients who had already had surgery, Moderna and Merck said Tuesday.

Dr. Drew Weissman and Katalin Karikó of the University of Pennsylvania Opinion: Thought mRNA vaccines would end with the pandemic? Think again The randomized trial included 157 patients with stage 3 or stage 4 melanoma who had already had surgery. Some patients received nine doses of the experimental cancer vaccine made by Moderna and the immunotherapy made by Merck every three weeks for about a year, and some received only the immunotherapy. Treatment with the experimental vaccine in combination with the immunotherapy reduced the risk of cancer recurrence or death by 44% compared with the immunotherapy alone, the companies said.

The preliminary results of a Phase 2b trial were shared in a news release and have not been peer-reviewed or published. The companies said they will publish the full data in the future and share results at an upcoming conference.

The companies said they will initiate a Phase 3 study in melanoma patients next year, and will study additional tumor types.

GET CNN HEALTH'S WEEKLY NEWSLETTER Sign up here to get The Results Are In with Dr. Sanjay Gupta every Tuesday from the CNN Health team.

“Today’s results are highly encouraging for the field of cancer treatment. mRNA has been transformative for COVID-19, and now, for the first time ever, we have demonstrated the potential for mRNA to have an impact on outcomes in a randomized clinical trial in melanoma,” Stéphane Bancel, chief executive officer for Moderna, said in a news release. Moderna is the maker of one of the mRNA Covid-19 vaccines used in the United States.

Moderna and Merck said serious treatment-related adverse events occurred in 14.4% of patients who received the vaccine and immunotherapy in the trial, and in 10% of patients who received only the immunotherapy. Keytruda has some known risks for serious side effects, the companies said.

Moderna’s experimental cancer vaccine, mRNA-4157/V940, is designed to prime patients’ immune system to generate a response to their specific tumors. Merck’s Keytruda, which is already used in the treatment of melanoma, stimulates the immune system to attack tumors.

According to the American Cancer Society, melanoma accounts for about 1% of all skin cancers, but it causes a majority of skin cancer deaths. It estimates that in 2022, about 100,000 new melanomas will be diagnosed, and more than 7,600 people will die from melanoma.




https://www.cnn.com/2022/12/13/health/mrna-cancer-vaccine-study/index.html#amp_tf=From%20%251%24s&aoh=16709572237947&csi=1&referrer=https%3A%2F%2Fwww.google.com&share=https%3A%2F%2Fwww.cnn.com%2F2022%2F12%2F13%2Fhealth%2Fmrna-cancer-vaccine-study%2Findex.html

Penn researchers find that the anesthetic and fast-acting antidepressant switches natural patterns of neuronal activity in the cerebral cortex. Ketamine, an established anesthetic and increasingly popular antidepressant, dramatically reorganizes activity in the brain, as if a switch had been flipped on its active circuits, according to a new study by Penn Medicine researchers. In a Nature Neuroscience paper, the team described starkly changed neuronal activity patterns in the cerebral cortex of animal models after ketamine administration—observing normally active neurons that were silenced and another set that were normally quiet suddenly springing to action. This ketamine-induced activity switch in key brain regions tied to depression may impact our understanding of ketamine’s treatment effects and future research in the field of neuropsychiatry.

“Our surprising results reveal two distinct populations of cortical neurons, one engaged in normal awake brain function, the other linked to the ketamine-induced brain state,” says the co-lead and co-senior author Joseph Cichon, an assistant professor of anesthesiology and critical care and neuroscience in the Perelman School of Medicine. “It’s possible that this new network induced by ketamine enables dreams, hypnosis, or some type of unconscious state. And if that is determined to be true, this could also signal that it is the place where ketamine’s therapeutic effects take place.”

Anesthesiologists routinely deliver anesthetic drugs before surgeries to reversibly alter activity in the brain so that it enters its unconscious state. Since its synthesis in the 1960s, ketamine has been a mainstay in anesthesia practice because of its reliable physiological effects and safety profile. One of ketamine’s signature characteristics is that it maintains some activity states across the surface of the brain (the cortex). This contrasts with most anesthetics, which work by totally suppressing brain activity. It is these preserved neuronal activities that are thought to be important for ketamine’s antidepressant effects in key brain areas related to depression. But, to date, how ketamine exerts these clinical effects remains mysterious.

“We were hoping to pinpoint exactly what parts of the brain circuit ketamine affects when it’s administered so that we might open the door to better study of it and, down the road, more beneficial therapeutic use of it,” says co-lead and co-senior author Alex Proekt, an associate professor of anesthesiology and critical care at Penn.




https://penntoday.upenn.edu/news/penn-medicine-how-ketamine-acts-switch-brain

Eating a high calorie diet can lead to weight gain and obesity. But the health consequences of diet depend partly on when in the day meals occur. Eating when you're normally inactive (night for humans) encourages obesity. This suggests that obesity results in part from a mismatch between meal timing and the natural day-night cycle, or circadian rhythm. But the mechanisms by which this happens aren’t fully understood.

n NIH-funded research team led by Dr. Joseph Bass at Northwestern University studied the metabolic effects of a high fat diet in mice when feeding was restricted to either daytime or nighttime. The results appeared in Science on October 20, 2022.

ince mice are nocturnal, they normally eat at night. Mice restricted to eating only at night gained less weight than mice restricted to eating only during the day or mice able to eat at any time. The night-fed mice also expended more energy and consumed more oxygen than day-fed mice. However, the different groups ate the same amount and had similar activity patterns. This suggested that the night-fed mice burned more calories by producing more heat.

o test this idea, the researchers genetically engineered mice to boost heat production by their fat tissue. These mice did not gain extra weight when fed during the daytime versus the nighttime. The mice also had higher levels of a nutrient called creatine in their fat cells. Creatine stores excess energy during times of low energy demand and releases it to power the cell during times of high demand. But creatine can also release its stored energy as heat in a process known as a futile creatine cycle.

he team wanted to test whether creatine was behind the effect of feeding time on weight gain. So, they studied the effect of time-restricted feeding in mice engineered to be creatine-deficient. In these mice, eating only at night did not reduce weight gain or increase energy expenditure compared to daytime eating.

hese results suggest that, as a result of nighttime feeding, more heat was produced from the energy stored in creatine. This, in turn, raised total energy use and reduced weight gain in the mice. It also suggests that circadian rhythms influence creatine metabolism. To test this idea, the researchers engineered mice with increased activity in genes that control circadian rhythms. These mice gained less weight on a high-fat diet and used more oxygen than control mice. They also had better glucose tolerance and increased futile creatine cycling.

igh-fat diets have been shown to suppress genes involved in circadian rhythms, particularly in fat tissue. These findings give further insights into the connections between diet, metabolism, and the body’s circadian clock. They also provide an explanation for the benefits of time-restricted feeding.

The clock is sensitive to the time people eat, especially in fat tissue, and that sensitivity is thrown off by high-fat diets,” Bass says. “We still don’t understand why that is, but what we do know is that as animals become obese, they start to eat more when they should be asleep. This research shows why that matters.”

by Brian Doctrow, Ph.D.




https://www.nih.gov/news-events/nih-research-matters/how-timing-eating-affects-metabolism-weight-gain

In the past decade, researchers have discovered a network of cells and vessels in and around the mammalian brain that help remove cellular waste and debris. Studies in mice found that, as the function of this system declines with age, toxic compounds can build up in the brain.

he brain also has its own population of immune cells. As in the rest of the body, these cells patrol for invading pathogens. They also help with tissue maintenance and repair.

n NIH-funded research team led by Drs. Antoine Drieu and Jonathan Kipnis from Washington University in St. Louis has been studying a key type of immune cell, called parenchymal border macrophages (PBMs), that interacts with the cerebrospinal fluid that flows in and out of the brain. Their new study was published on November 9, 2022, in Nature.

o see if PBMs may have a role in regulating the flow of cerebrospinal fluid, the researchers used fluorescent tracers to examine the brains of mice. They found PBMs closely associated with the tracers moving in and out of the brain in cerebrospinal fluid. They also identified different types of PBMs, one of which serves as a waste scavenger.

hen the team injected mice with a drug that depleted PBMs, the flow of cerebrospinal fluid through the brain was substantially reduced one week later. When they tracked cerebrospinal fluid flow in real time in the mice using magnetic resonance imaging, they saw similar results. The researchers also saw buildup of several proteins that have been associated with Alzheimer’s in the mice with depleted PBMs.

urther work showed that, when the brain lost PBMs, the activity of enzymes called MMPs also decreased. This led to accumulation of extracellular matrix along vessels and capillaries. Extracellular matrix provides structure for the vessels that carry fluid through the body. But too much can make vessels overly stiff, impeding fluid flow. Correspondingly, the researchers found that vessels in the brains of mice with depleted PBMs didn’t expand normally.

he team next compared PBM levels in young and aged mice. Aged mice had fewer of the scavenger PBMs. Aged mice also had a greater accumulation of extracellular matrix in the brain. When the researchers injected aged mice with a substance that can activate PBMs, levels of MMP enzymes and fluid flow both increased, while the amount of extracellular matrix decreased.

hen the researchers depleted PBMs in a mouse model of Alzheimer’s, those mice developed more amyloid beta plaques—one of the hallmarks of the disease—than the same type of mice with normal levels of PBMs. Finally, the team looked at immune cells collected from the brains of people with an inherited form of Alzheimer’s. The PBMs from people with the disease had changes in gene expression that reflected decreased function compared with unaffected family members.

Cerebrospinal fluid flow is impaired in numerous neurodegenerative diseases, such as Alzheimer’s, stroke, Parkinson’s, and multiple sclerosis,” Drieu says. “If we can restore fluid flow through the brain just by boosting these macrophages, maybe we can slow the progression of these diseases.” More work in animal models will be needed before such an approach could be tested in people.

by Sharon Reynolds




https://www.nih.gov/news-events/nih-research-matters/immune-cells-control-waste-clearance-brain

The effects of COVID-19 can persist long after the initial symptoms of the illness are gone. These effects, called post-acute sequelae of COVID-19 (or PASC), can include brain fog, fatigue, headaches, dizziness, and shortness of breath. Long COVID—when symptoms last weeks or months after the acute infection has passed—affects about 2.5% of COVID patients. While patients who were hospitalized are more susceptible, even those with mild cases can experience Long COVID.

research team led by Drs. Benjamin tenOever at the NYU Grossman School of Medicine and Venetia Zachariou at the Icahn School of Medicine at Mount Sinai set out to understand the underlying biology of Long COVID. The researchers, who were supported in part by NIH, studied the golden hamster, a widely used small animal model for respiratory infections. The hamsters were exposed to SARS-CoV-2 via their nostrils. For comparison, another group was exposed to a flu virus, influenza A. Various samples were taken for analysis after 3, 14, and 31 days of infection.

issues from human donors who had COVID-19 at the time of death or had recovered from COVID-19 but died from other causes were also sampled and analyzed. Results appeared on June 7, 2022, in Science Translational Medicine.

oth SARS-CoV-2 and influenza A infections were largely cleared within two weeks, similar to the course of recovery in humans. Following SARS-CoV-2 infection, however, animals showed much more extensive lung damage and slower recovery than those exposed to influenza A. Those exposed to SARS-CoV-2 also had more kidney damage.

hen the scientists sampled different parts of hamster brains to analyze gene activity, they found that SARS-CoV-2 had unique effects on the hamster olfactory system—the parts of the nose and brain responsible for smell. The olfactory epithelium, the lining inside the nose, showed signs of extensive inflammation long after the virus could be detected. SARS-CoV-2 also caused high levels of inflammation in the olfactory bulb, a part of the brain involved in processing smell as well as in emotion and learning. Inflammation in these areas persisted long after the infection was cleared.

nterestingly, chronic inflammation in the olfactory system correlated with behavioral changes in the hamsters thought to reflect mood disorders like depression and anxiety. Although olfactory bulb tissue from people who recovered from COVID-19 and died of other causes is difficult to obtain, the few samples studied were comparable to that of the hamsters. This suggests that the inflammation seen in the hamsters may explain the mechanism responsible for symptoms of Long COVID in people. Further research is needed to fully understand the link between brain inflammation, brain activity, and behavioral changes.

[T]his study suggests that the molecular mechanism behind many Long COVID-19 symptoms stems from this persistent inflammation while describing an animal model close enough to human biology to be useful in the design of future treatments,” tenOever says.

by Larisa Gearhart-Serna, Ph.D.




https://www.nih.gov/news-events/nih-research-matters/long-covid-symptoms-linked-inflammation

People with mild infections who lost their sense of taste and smell were more likely to have antibodies to help combat the virus, a new study suggests.

Lisa Rapaport By Lisa Rapaport December 14, 2022 Fact-Checked

covid altered taste and smell could help in future infections Loss of smell and taste has become a less common symptom as COVID-19 evolves and the population acquires immunity through vaccination and prior infection. Luis Velasco/Stocksy Some people who lose their sense of taste or smell due to a COVID-19 infection may have an easier time fighting off the virus in the future, a new study suggests.

For the study, conducted in 2020 at NewYork-Presbyterian/Columbia University Irving Medical center in New York City, scientists tested 266 people for antibodies to COVID-19 at least two weeks after their symptoms were mostly gone and they no longer showed signs of active infection. None of the subjects had experienced severe cases, or had any signs of acute infection when they were tested for antibodies, and they had no lingering symptoms other than a potential loss of taste or smell.

Overall, almost two-thirds of participants reported either an impaired sense of smell or taste, and 58 percent said both senses were altered by the virus.

Compared with people who never lost their sense of taste or smell, those who did were roughly twice as likely to test positive for virus-fighting antibodies, the researchers reported in the journal PLoS One.

Fever, Cough, Runny Nose Were Not Linked to Antibody Protection Other COVID-19 symptoms that were predominant in 2020, such as fever, cough, sneezing, runny nose, and difficulty breathing didn’t appear to influence whether people had antibodies after they recovered from an acute infection.

This suggests that loss of taste and smell are strong predictors of a longer-lasting ability to fight the virus, the study team concluded.

One limitation of study, the researchers noted, is that they relied on patients to accurately recall and report on whether they lost their sense of taste or smell when they were sick. Another drawback is that it’s possible some people only reported a loss of taste because their sense of smell was altered, compromising their ability to distinguish different flavors in the food they ate.

The study also wasn’t a controlled experiment designed to prove whether the loss of taste and smell directly causes higher antibody levels — or that it always helps prevent future infections.

Do Antibodies Really Help Prevent COVID-19 Reinfection? Despite the study’s limitations, it does jibe with other research that found a link between the presence of antibodies after a bout of COVID-19 and a lower risk of reinfection.

One study published in 2021 found that people with negative antibody tests were 10 times more likely to get a second COVID-19 infection after three months. Another study published in 2021 followed individuals from three to six months after a mild COVID-19 infection and found that not one person with antibodies got reinfected — and that nearly all of these people retained high levels of antibodies after six months.




https://www.everydayhealth.com/coronavirus/losing-taste-and-smell-due-to-covid-19-tied-to-lower-reinfection-risk/?slot=1&eh_uid=86162201&xid=nl_EHNLdailynews_2022-12-14_29985325&utm_source=Newsletters&nl_key=nl_daily_health_news&utm_content=2022-12-14&utm_campaign=Daily_Health_News&zdee=gAAAAABikMTRaz8Vnrpnsej4aOmAPHCzspDYk-pJmMdHR-5IdEBG39oQrpCDvkbBYIxn3XRLz6IJcWtaPt6P5t7i2bhuIvxFnye9_CDRT8Pmf6Z2wdp9uDLnOEH-MFhwMpnoPEnmCn7T

When a company announces a recall, market withdrawal, or safety alert, the FDA posts the company's announcement as a public service. FDA does not endorse either the product or the company.

Share Tweet Linkedin Email Print Summary Company Announcement Date: December 21, 2022 FDA Publish Date: December 21, 2022 Product Type: Drugs Reason for Announcement: Presence of nitrosamine impurity, N-Nitroso-Quinapril Company Name: Lupin Pharmaceuticals Inc. Brand Name: Lupin Product Description: Quinapril 20 and 40 mg tablets Company Announcement Baltimore, Maryland, December 21, 2022: Lupin Pharmaceuticals Inc. is voluntarily recalling four (4) lots of Quinapril Tablets to the patient (consumer/user) level due to the presence of a nitrosamine impurity, N-Nitroso-Quinapril, observed in recent testing above the Acceptable Daily Intake (ADI) level. To date, Lupin has received no reports of illness that appear to relate to this issue.

Lupin discontinued the marketing of Quinapril tablets in September 2022.

Nitrosamines are common in water and foods, including cured and grilled meats, dairy products and vegetables. Everyone is exposed to some level of nitrosamines. These impurities may increase the risk of cancer if people are exposed to them above acceptable levels over long periods of time.

Quinapril tablet USP is an angiotensin-converting enzyme (ACE) inhibitor indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. Quinapril Tablets USP 20mg, and 40mg is packaged in 90 count bottles and was distributed nationwide in the US to wholesalers, drug chains, mail order pharmacies and supermarkets. The recalled lots are included in the table below:

Product Lot No Expiry NDC UPC Distribution Dates Quinapril Tablets USP, 20mg G102929 04/2023 68180-558-09 (90’s) 368180558095 03/15/2021 – 09/01/2022 Quinapril Tablets USP, 40mg G100533 G100534 G203071 12/2022 12/2022 03/2024 68180-554-09 (90’s) 368180554097 Lupin Pharmaceuticals Inc. is notifying its wholesalers, distributors, drug chains, mail order pharmacies and supermarkets by phone and through recall notification and is arranging for the return of all the recalled product lots.

Patients taking, Quinapril Tablets USP, 20mg, and 40mg are advised to continue taking their medication and contact their pharmacist, physician, or medical provider for advice regarding an alternative treatment.

Wholesalers, distributors and retailers that have Quinapril Tablets USP, 20mg, and 40mg that are being recalled should discontinue distribution of the recalled product lots immediately.

Consumers, wholesalers, distributors, and retailers with questions regarding this recall should contact Inmar Rx Solutions, Inc. at (877) 538-8445 Monday – Friday 09:00 am to 05:00 pm EST. For reimbursement, please have the recalled lots returned to Inmar Rx Solutions, Inc.; the lot number can be found on the side of the bottle label.

Adverse reactions or quality problems experienced with the use of this product may be reported to the FDA's MedWatch Adverse Event Reporting program either online, by regular mail or by fax.

Complete and submit the report Online: www.fda.gov/medwatch/report.htm Regular Mail or Fax: Download form www.fda.gov/MedWatch/getforms.htm or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178 https://www.fda.gov/safety/report-problem-fda This recall is being conducted with the knowledge of the U.S. Food and Drug Administration.

Product Label: (see images below)

About Lupin Pharmaceuticals

Lupin Pharmaceuticals, Inc. is the U.S. based wholly-owned subsidiary of Lupin Limited and is the 3rd largest pharmaceutical company in the U.S. based on total prescriptions. Together, all Lupin-owned entities combine to make up the 8th largest generic pharmaceutical company in the world by revenue size. Lupin Pharmaceuticals, Inc. is dedicated to delivering high-quality medications across many treatment areas. Lupin Pharmaceuticals Inc.’s branded pharmaceuticals division, is the provider of products designed to help prevent and manage women’s health conditions with serious health consequences.

Company Contact Information Consumers: Inmar Rx Solutions, Inc. 877-538-8445




https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/lupin-pharmaceuticals-inc-issues-voluntary-nationwide-recall-four-lots-quinapril-tablets-due?utm_medium=email&utm_source=govdelivery

Enacting Medicaid expansion in Texas and increasing the use of preventive and antiviral medications could result in a decline of new HIV infections among young Black gay, bisexual, and other men who have sex with men (MSM) in Houston, reports a study in the January issue of Medical Care. The journal is published in the Lippincott portfolio by Wolters Kluwer.

Expanding Medicaid, as a number of states have already done, may help substantially reduce the burden of HIV among underserved populations in Houston and throughout Texas, according to the social network modeling and computer simulation study by lead author Francis Lee, PhD, of the University of Chicago and colleagues. However, the researchers note that additional strategies – focused on increasing the use of antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) for HIV – would be needed to meet the ultimate goal of eliminating HIV transmission in the city.

Medicaid expansion could reduce high rates of HIV transmission among young Black gay, bisexual, and other MSM The analysis focused on HIV transmission among young (18 to 34 years) Black gay, bisexual, and other MSM: a disproportionately affected group who account for 19% of all newly diagnosed people in Houston. Along with other interrelated social determinants of health factors such as race, sexual identity, and medical distrust, lack of medical coverage is a key contributor to the high rate of HIV transmission among young Black gay, bisexual, and other MSM, according to other published research cited in the paper.

Expansion of Medicaid coverage under the Affordable Care Act has led to numerous population health benefits, including increased use of effective ART drugs for treatment of HIV infection and PrEP drugs to prevent HIV transmission among people at risk, according to other published research cited in the paper. Texas is one of 11 states that have not adopted Medicaid expansion. That leaves the state as a whole as well as Houston – the most populous city in the Southern United States – with massive coverage gaps that disproportionately burden people of color, according to the authors.

Related Stories Study reveals major problems and gaps in Canada's process of mandatory HIV screening of migrants Multi-stage HIV vaccine regimen shows promising results in Phase 1 clinical trial HIV-positive people are protected by Covid vaccines Dr. Lee and colleagues used a technique called agent-based network modeling to simulate the effects of alternative Medicaid expansion strategies on HIV transmission among young Black gay, bisexual, and other MSM in Houston. Simulations projected the effects of Medicaid expansion alone and with the addition of two further strategies that have shown promise in increasing engagement with ART and PrEP.

Study model project possible decrease of HIV incidence rate to almost 50% In the study models, all three Medicaid expansion scenarios were projected to lead to considerable declines in HIV transmission among young Black gay, bisexual, and other MSM. With Medicaid expansion alone, the HIV incidence rate (new cases per 100 uninfected) was projected to decrease by 17.5% in the tenth year, while the number of new infections would decrease by 14.9%.

The most ambitious strategy examined for increasing the use of ART and PrEP, according to the modeling, would reduce the HIV incidence rate by 48.7% within 10 years, while reducing the number of new infections by 44.0% over the same period. While Medicaid expansion alone may not get Houston to the goal of zero incidence, expanding PrEP and ART interventions in combination may help achieve this goal, Dr. Lee and coauthors write.

The researchers note that Houston has made substantial strides closer to goals aimed at ending the HIV epidemic, focused on increasing the uptake of PrEP and ART. Improved ART and PrEP engagement have shown promise in reducing HIV transmission in a number of US populations that bear a disproportionate burden of the epidemic, Dr. Lee and colleagues write.

In another sign of progress, the researchers cite a recent federal mandate requiring nearly all insurance plans to provide coverage for PrEP without cost-sharing. [H]owever, Dr. Lee and colleagues add, without concerted efforts to reach the uninsured, this change has the potential to increase rather than to decrease the disparities in HIV incidence that disproportionately affect Black MSM.

Source: Wolters Kluwer

Journal reference: Lee, F., et al. (2022) Expanding Medicaid to Reduce Human Immunodeficiency Virus Transmission in Houston, Texas. Insights From a Modeling Study. Medical Care. doi.org/10.1097/MLR.0000000000001772.




https://www.news-medical.net/news/20221213/Medicaid-expansion-and-increase-in-PrEP-antiretroviral-treatment-could-result-in-decline-of-new-HIV-infections.aspx#amp_tf=From%20%251%24s&aoh=16709607670230&csi=0&referrer=https%3A%2F%2Fwww.google.com&share=https%3A%2F%2Fwww.news-medical.net%2Fnews%2F20221213%2FMedicaid-expansion-and-increase-in-PrEP-antiretroviral-treatment-could-result-in-decline-of-new-HIV-infections.aspx

The percentage of adolescents reporting substance use in 2022 largely held steady after significantly declining in 2021, according to the latest results(link is external) from the Monitoring the Future survey(link is external) of substance use behaviors and related attitudes among eighth, 10th, and 12th graders in the United States. Reported use for almost all substances decreased dramatically from 2020 to 2021 after the onset of the COVID-19 pandemic and related changes like school closures and social distancing. In 2022, reported use of any illicit drug within the past year remained at or significantly below pre-pandemic levels for all grades, with 11% of eighth graders, 21.5% of 10th graders, and 32.6% of 12th graders reporting any illicit drug use in the past year.

The Monitoring the Future survey is conducted each year by researchers at the University of Michigan, Ann Arbor, and funded by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health.

“The Monitoring the Future Survey is one of the best and most timely tools we have to monitor and understand changes in substance use among young people over time, including through historic events such as the COVID-19 pandemic,” said Nora Volkow, M.D., NIDA director. “It is encouraging that we did not observe a significant increase in substance use in 2022, even as young people largely returned to in-person school, extracurricular activities, and other social engagements.”

The Monitoring the Future survey is given annually to students in eighth, 10th, and 12th grades who self-report their substance use behaviors over various time periods, such as past 30 days, past 12 months, and lifetime. The survey also documents students’ perception of harm, disapproval of use, and perceived availability of drugs. Notably, the survey results are released the same year the data are collected.

From February through June 2022, the Monitoring the Future investigators collected 31,438 surveys from students enrolled across 308 public and private schools in the United States. The completed survey from 2022 is nationally representative and represents about 75% of the sample size of a typical year’s data collection. The Monitoring the Future investigators noted that schools opt-in to participate in the survey, and some schools that normally participate opted-out this year as they continued to operationally recover from the pandemic. All participating students took the survey via the web – either on tablets or on a computer – with between 95-99% of respondents taking the survey in-person in school.

The survey found that adolescents most commonly reported use of alcohol, nicotine vaping, and cannabis in the past year, and levels generally held steady with those reported in 2021. For substances where reported past-year use did increase between 2021 and 2022, the vast majority of reported use remained at or below the pre-pandemic levels observed in 2020. Compared to levels observed in 2021, data reported in 2022 show:

Nicotine vaping remained stable for all three grades surveyed, with 12% of eighth graders, 20.5% of 10th graders, and 27.3% of 12th graders reporting vaping nicotine in the past year. Cannabis use also remained stable for all three grades surveyed, with 8.3% of eighth graders, 19.5% of 10th graders, and 30.7% of 12th graders reporting cannabis use in the past year. Of note, 6.0% of eighth graders, 15.0% of 10th graders, and 20.6% of 12th graders reported vaping cannabis within the past year, reflecting a stable trend at the pre-pandemic level among eighth and 12th graders, and a small increase in reported use among 10th graders, though reported use among 10th graders in 2022 is still significantly below pre-pandemic levels. Alcohol use remained stable for eighth and 10th graders (with 15.2% and 31.3% reporting use in the past year, respectively) but returned to pre-pandemic levels for 12th graders in 2022 (with 51.9% of 12th graders reporting alcohol use in the past year). Any illicit drug use other than marijuana also remained stable for all three grades surveyed, with 4.9% of eighth graders, 5.7% of 10th graders, and 8.0% of 12th graders reporting any illicit drug use other than marijuana in the past year. These data build on long-term trends documenting low and fairly steady use of illicit substances reported among teenagers – including past-year use of cocaine, heroin, amphetamines, and nonmedical use of prescription drugs, generally. Use of narcotics other than heroin (including Vicodin, OxyContin, Percocet, etc.) increased slightly among 12th graders between 2021 and 2022 (with 1.7% of 12th graders reporting use within the past year), consistent with the pre-pandemic levels observed in 2019 and 2020 (2.7% and 2.1%, respectively). When asked a range of questions about the perceived harmfulness of occasionally taking specific prescription medications (such as OxyContin and Vicodin), or the risk of “narcotics other than heroin” overall, the percentage of students who reported perceiving a “great risk” ranged from 22.9% among eighth graders to 52.9% among 12th graders. The percentage of respondents who reported perceiving a “great risk” associated with taking Adderall occasionally ranged from 28.1% among eighth graders to 39.6% among 12th graders.

Though the data have indicated stable or declining use of illicit drugs among young people over many years, other research has reported a recent dramatic rise in overdose deaths(link is external) among young people ages 14-18. This increase is largely attributed to illicit fentanyl, a potent synthetic drug, contaminating the supply of counterfeit pills made to resemble prescription medications like benzodiazepines, ADHD medications, and opioids.

“The proliferation of fentanyl in the drug supply is of enormous concern. Though the data indicate that drug use is not becoming more common among young people than it has been in the past, the tragic increase in overdose deaths among this population suggest that drug use is becoming more dangerous than ever before,” said Dr. Volkow. “It is absolutely crucial to educate young people that pills purchased via social media, given to someone by a friend, or obtained from an unknown source may contain deadly fentanyl.”

The results were gathered from a nationally representative sample, and the data were statistically weighted to provide national numbers. This year, 11% of the 12th grade students who took the survey identified as African American, 22% as Hispanic, 5% as Asian, 1% as American Indian or Alaska Native, 47% as white, 1% as Middle Eastern, and 14% as more than one of the preceding categories. The survey also asks respondents to identify as male, female, other, or prefer not to answer. For the 2022 survey, 48% of 12th grade students identified as male, 47% identified as female, 1% identified as other, and 4% selected the “prefer not to answer” option.

“We were curious to see whether the significant decreases in substance use we observed last year would continue into the future, and we now see that there may indeed be a longer lasting impact for some substances,” said Richard A. Miech, Ph.D., team lead of the Monitoring the Future study at the University of Michigan. “The fact that cannabis use and nicotine vaping did not appear to return to pre-pandemic levels in 2022 is a fascinating data point. Moving forward, it will be important to continue to monitor these trends to understand the impact on future drug use behavior and outcomes.”

The 2022 Monitoring the Future data tables(link is external) highlighting the survey results are available online from the University of Michigan.

For more information on substance and mental health treatment programs in your area, call the free and confidential National Helpline 1-800-662-HELP (4357) or visit www.FindTreatment.gov(link is external).




https://www.nih.gov/news-events/news-releases/most-reported-substance-use-among-adolescents-held-steady-2022

HEALTH 16 December 2022 ByKIM MEREDITH-JONES, THE CONVERSATION Broken Bone Xray (Peter Dazeley/Getty Images) Breaking a bone in childhood is not just a rite of passage. It could be a warning sign of future fracture risk and osteoporosis.

A history of prior fractures is one of the strongest predictors of future fractures, yet current guidelines used to determine osteoporosis risk ignore childhood fractures.

We investigated the history of fractures in a group of middle-aged people who are part of the Dunedin Study, a comprehensive longitudinal project that has continued for five decades.

We found people who broke a bone more than once in their childhood had more than double the odds of breaking a bone as an adult. In women, this also resulted in lower bone density at the hip at age 45.

The people in our study are young for investigating fracture risk and osteoporosis, but if lifestyle changes to improve bone density can be implemented earlier in life, it may have the greatest impact on lifelong bone health and the reduction of osteoporosis risk.

Childhood fractures predict osteoporosis risk About one in two children break a bone during childhood, with almost a quarter of boys and 15 percent of girls suffering multiple fractures. But we don't currently fully understand why some children repeatedly break bones or whether this will predict adult bone health.

There are several reasons why children fracture a bone.

Previous research has shown that kids who fracture tend to live in poorer households, have high levels of vigorous exercise, are overweight or have a high body mass index, vitamin D insufficiency, low calcium intakes, and may experience physical abuse.

Children who fracture repeatedly may also have especially fragile skeletons, they may be accident-prone, or their bone fractures may occur during sport or physical activity.

But an important question is whether kids who break bones have temporary reductions in bone strength during rapid growth, or if these bone weaknesses continue into adulthood.

The people we studied are all part of the unique Dunedin Study, which tracked the development of a thousand babies born in Behavioral Dunedin between April 1972 and March 1973.

Study members have been assessed repeatedly every few years since, on a wide range of topics including risk-taking behaviors, sport participation, physical abuse, child and adult deprivation, among others.

They've also repeatedly undergone face-to-face interviews asking about injuries, including fractures since they were children. This means we can compare their medical fracture history in middle age with their own recollections from childhood.

Importantly, because the Dunedin Study also collects comprehensive information about other factors that may explain why some children suffered repeated fractures, we could include these aspects in our analyses.

What we found Both boys and girls who suffered more than one fracture as a child were more than twice as likely to fracture as an adult. Also, those who were fracture-free in childhood tended to stay so in adulthood.

Among females, childhood fractures were associated with lower bone mineral density at the hip later in life, but this was not the case among males.

Many other studies have sought to determine whether children who sustain a single fracture during childhood have skeletal fragility that persists into adulthood. Our study is the first to demonstrate an increased risk of adult fracture in both males and females who repeatedly fracture in childhood.

Exactly why this is the case is not clear though. The persistent risk was not associated with other behavioral factors, such as risky behavior, demographics, obesity, childhood abuse, or sports participation.

Why this matters Although we don't know the exact mechanisms for this increased risk of fracture in adulthood, the results could be used to raise awareness for those most at risk.

Parents of children who repeatedly fracture in childhood should be informed about various ways to prevent persistent skeletal fragility with age.

Behavioral changes such as increased weight-bearing activity, optimal intake of calcium and vitamin D, and increased protein and dairy consumption are all beneficial interventions that can be initiated early and maintained throughout the lifespan.

Osteoporosis tends to affect adults after middle age. We hope to continue investigating the relationship between childhood fractures and adult bone health in this very special population of people as they age, to find out whether these links persist after menopause in women or affect lifelong risk in men.The Conversation

Kim Meredith-Jones, Senior Research Fellow, University of Otago




https://www.sciencealert.com/mysterious-pattern-emerges-in-the-future-of-children-who-break-bones

More than 1 million new HIV infections occur each year. Ending the global HIV/AIDS pandemic will require an effective HIV vaccine. Vaccines work by inducing the immune system to make antibodies that can neutralize a particular pathogen. But doing so for HIV has been challenging because there are countless variants worldwide, and the immune system doesn’t normally make antibodies that can protect against a wide range of them.

More than a decade ago, researchers at the Vaccine Research Center of NIH’s National Institute of Allergy and Infectious Diseases discovered a class of rare antibodies called broadly neutralizing antibodies (bnAbs) against HIV. These could neutralize many HIV strains at once. The bnAbs have been shown to prevent HIV infection in animals and humans. But inducing bnAbs with a vaccine has proven difficult. This is because bnAb-precursor B cells—the immune cells that develop into bnAb-producing B cells—are only rarely activated by the envelope proteins that form a protective coating for HIV.

One strategy to produce bnAbs involves specifically stimulating these rare precursor B cells. To do this, researchers led by Dr. William Schief at the Scripps Research Institute engineered a molecule based on a region of the HIV envelope protein called the CD4 binding site. They developed a modified protein to prime the precursor B cells to react. The protein, called eOD-GT8, was designed to incorporate into a self-assembling nanoparticle with 60 copies. The nanoparticle vaccine was previously shown to induce production of bnAb precursors in mice.

Based on this evidence, a research team led by Drs. Juliana McElrath at the Fred Hutchinson Cancer Center, Adrian McDermott at NIH’s Vaccine Research Center, and Schief conducted a phase 1 clinical trial of the eOD-GT8 vaccine to begin assessing its safety and efficacy in people. Results appeared in Science on December 2, 2022.

Forty-eight participants were immunized with either a low or high dose of the vaccine or a placebo. Immunization consisted of two doses, given eight weeks apart. The vaccine had a favorable safety profile, with no serious adverse events reported.

Before and after vaccination, the researchers measured the presence in participants’ blood and lymph nodes of bnAb-precursor B cells targeting eOD-GT8. They found that these cells increased in 97% of vaccine recipients after at least one of the two doses. Frequencies of these B cells increased by more than 500-fold compared to before vaccination.

The team also examined the receptors that B cells use to recognize pathogens. These receptors resemble antibodies and recognize their targets in a similar way. Receptors on the eOD-GT8-targeting bnAb-precursor B cells shared several molecular features with bnAbs. The team also saw early steps in the development of bnAbs. These include an increase in mutations in the receptor genes after the second vaccine dose and an increase in the affinity of the receptors for the vaccine.

These findings establish proof of concept and a crucial first step for the strategy of eliciting bnAbs against HIV. But this priming vaccine alone cannot induce production of mature bnAbs. Booster vaccines will be needed to elicit bnAb production and protection against HIV. The results support further development of such boosters.

“This trial and additional analyses will help inform design of the remaining stages of a candidate HIV vaccine regimen—while also enabling others in the field to develop vaccine strategies for additional viruses,” McElrath says.

—by Brian Doctrow, Ph.D.




https://www.nih.gov/news-events/nih-research-matters/progress-toward-eventual-hiv-vaccine

The fall and winter flu season may bring out dishonest sellers hawking fraudulent products to unsuspecting consumers.

ome of these sellers illegally offer unproven products that claim to prevent, mitigate, treat, or cure the flu – even though they have not been evaluated or approved by the U.S. Food and Drug Administration for safety and effectiveness. These products can be found online, including popular marketplaces, and in retail stores. They may be labeled as dietary supplements, foods, hand sanitizers, nasal sprays, or devices.

hese products might be dangerous to you and your family. The FDA urges consumers to avoid fraudulent flu products and offers some tips on how to spot them.

Flu Vaccine Is the Best Prevention Flu is a serious disease, caused by influenza viruses, that can lead to hospitalization and even death. Getting a flu vaccine is the best way to prevent this infectious disease and its serious complications.

he Centers for Disease Control and Prevention recommend that everyone age 6 months and older get vaccinated every year against influenza. This is particularly so for people at an increased risk for serious complications, including young children, adults 65 years and older, and those with chronic medical conditions. For more information on flu vaccine recommendations, visit this CDC page.

he FDA has approved numerous vaccines for the prevention of influenza. To find a flu vaccine near you, visit this page.

DA-Approved Antiviral Medications for Flu If you do get the flu, there are FDA-approved antiviral drugs, available by prescription from your health care professional, to treat it. There are several FDA-approved antiviral drugs recommended by the CDC for use against circulating influenza viruses. These drugs work best if started soon after the onset of symptoms (within 48 hours).

lu antiviral medications are used to prevent or treat flu and are available by prescription in the form of pills, liquids, inhalers, and intravenous infusion. The various products are all approved for adolescent and adult use, and they differ in the ages for which they are approved to treat infants and children, ranging from 2-weeks-old to age 12.

f you get the flu, antiviral medications can make your illness milder and may make you feel better faster. Antiviral medications work best when started within the first two days of getting sick.

f you are exposed to the flu, antiviral medication can help prevent you from becoming sick. Talk to your health care professional if you have been or may be near a person with the flu.

f you think you have the flu, talk to your health care professional. There are FDA-approved drugs to help with the flu.

ypes of Fraudulent Flu Products There are no legally marketed over-the-counter (OTC, or non-prescription) drugs to prevent, treat, or cure the flu. But there are legally marketed OTC drugs to reduce fever and to relieve muscle aches, congestion, and other symptoms typically associated with the flu.

ietary supplements, conventional foods (such as some herbal teas), or devices (such as certain air filters and light therapies) that fraudulently claim to prevent, mitigate, treat, or cure the flu have not been evaluated by the FDA for safety and effectiveness.

he FDA is particularly concerned that fraudulent products might cause people to delay, forgo, or stop the medical treatment they need, leading to serious and life-threatening harm. The ingredients in fraudulent products could lead to unexpected side effects and interactions with other medications people may be taking.

rotect yourself and your family by looking out for potentially fraudulent flu and antiviral products being sold without a prescription, which may claim to:

educe the severity and length of flu or other viral infections. Boost your immunity naturally without a flu vaccine. Act as a safe and effective alternative to the flu vaccine. Prevent catching the flu or viral infections. Be an effective treatment for flu or viral infections. Provide faster recovery from the flu or viral infections. Support your body’s natural immune defenses to fight off flu or other viruses. Find Out if Your Online Pharmacy Is Safe Fraudsters take advantage of unsuspecting people through websites appearing to be online pharmacies selling prescription drugs.

egitimate online pharmacies do exist. But so do many websites that look like safe online pharmacies but are actually fraudulent and engaging in illegal activity. These websites may be selling unapproved drugs that may be dangerous.

nsure about an online pharmacy? Visit the FDA’s BeSafeRx campaign to learn how to safely buy prescription medicines online. If you have a question about a treatment or product, talk to your doctor or other health care professional.

here Are No FDA-Approved Homeopathic Products At your pharmacy and online, you may see products being sold and advertised as homeopathic. The FDA is not aware of any proven benefits of these products.

omeopathic products are generally labeled as containing very small amounts of highly diluted substances, including ingredients from plants, animal or human sources, bacteria, minerals, and chemicals. The FDA has found that some of these products contain active drug ingredients in levels that far exceed the amount stated on the product’s label and could cause significant harm to children. Therefore, we urge caution if you are thinking about giving homeopathic flu, cough, and cold medicines to children.

here are no FDA-approved homeopathic products. Homeopathic products sold in the U.S. have not been approved by the FDA for any use and may not meet modern standards for safety, effectiveness, and quality.




https://www.fda.gov/consumers/consumer-updates/protect-your-family-fraudulent-flu-products?utm_medium=email&utm_source=govdelivery

In a recent study published in Cell, researchers demonstrated the exceptional immune evasion properties of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants, BQ and XBB.

Study: Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. Image Credit: Naeblys/Shutterstock Study: Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. Image Credit: Naeblys/Shutterstock Background To date, XBB and XBB.1 and BQ.1, and BQ.1.1 represent the most resistant SARS-CoV-2 variants. BQ subvariants have evolved from Omicron BA.5, whereas XBB subvariants are recombinants of Omicron BA.2-derived, BA.2.75, and BJ.1 sublineages.

Interestingly, these variants have accumulated multiple spike (S) mutations and continue to diversify and evolve. For instance, XBB has 14 S mutations more than parental strain BA.2, including five and nine in the N-terminal domain (NTD) and receptor-binding domain (RBD), respectively, while XBB.1 has an extra G252V mutation.

About the study In the present study, researchers evaluated the neutralization of XBB, XBB.1, BQ.1, and BQ.1.1 by sera from five cohorts. The first two cohorts comprised individuals who received three doses plus a fourth booster dose of messenger ribonucleic acid (mRNA)-based COVID-19 vaccines. They referred to these two cohorts as 3 shots WT/4 shots WT. The next cohort had recipients of three doses of one of the COVID-19 mRNA vaccines, who also received a fourth booster of recently authorized bivalent mRNA vaccines (3 shots WT + bivalent). The remaining two cohorts had individuals with BA.2 and BA.4/5 breakthrough infections.

The researchers used the findings of serum neutralization tests to construct an antigenic map that showcased the antigenic distances among D614G, the wildtype SARS-CoV-2 variant, and the Omicron subvariants.

The team constructed pseudoviruses for each subvariant and every mutation found in the subvariants. Then, they evaluated those against a panel of 23 monoclonal antibodies (mAbs) targeting SARS-CoV-2 S epitopes. This panel mainly had mAbs with substantial neutralizing activity against Omicron, for instance, bebtelovimab. It also had the therapeutic mAb cocktail Evusheld, a combination of mAbs, COV2-2196, and COV2-2130.

Study findings Relative to ancestral strain D614G, serum neutralization titers against XBB, XBB.1, and BQ.1, BQ.1.1 had diminished by >37-fold to >71-fold in the “3 shots WT” cohort. Moreover, most samples did not neutralize these new subvariants at 1:100 serum dilution. Conversely, geometric mean titers (GMTs) of sera from the two breakthrough cohorts were markedly higher. The antigenic map showed that BA.5-derivative BQ.1.1 had drifted from its parental strain as much as the latter had from D614G; eventually, it became almost six times more neutralization resistant than BA.5.

Antibodies eBook Antibodies Industry Focus eBook Compilation of the top interviews, articles, and news in the last year. Download a free copy Interestingly, each unit of antigenic drift made a two-fold difference in serum neutralization susceptibility of a SARS-CoV-2 variant. Accordingly, XBB.1 was ~63-fold more resistant to neutralization than its parent strain. It is by far the most antigenically distinct Omicron subvariant too.

Both bebtelovimab and Evusheld failed to neutralize BQ.1 or BQ.1.1. Likewise, the BQ subvariants showed complete resistance to RBD class 1 and 3 mAbs, under the effects of N460K mutation, and the R346T and K444T mutations, respectively. Since BQ.1.1 had an additional R346T mutation, it more strongly evaded RBD class 3 mAbs than BQ.1. The shared S mutations among BQ.1.1, XBB, and XBB.1 suggested convergent evolution to evade antibodies attacking these S regions. Lastly, BQ and XBB subvariants S proteins have comparable binding affinities to human angiotensin-converting enzyme 2 (hACE2) as their predecessor, suggesting they mutated for better fitness. Still, there were other factors were at play as well.

Conclusions Overall, vaccination with or without prior SARS-CoV-2 infection and even booster shots of novel bivalent (WA1-BA.5) mRNA vaccines did not confer protection against any of the four Omicron XB and BQ subvariants. Furthermore, the researchers found the extent of their antigenic drift quite alarming. The current and previous findings on the serum neutralization of some sarbecoviruses indicated that XBB and XBB.1 are much more distant than sarbecoviruses.

Together, these findings highlighted that the recently emerged Omicron BQ and XB subvariants could further compromise the efficacy of current COVID-19 vaccines, which, in turn, could surge breakthrough infection and re-infection cases. Unfortunately, since BQ and XBB sublineages are resistant to bebtelovimab, the only active mAb against circulating SARS-CoV-2 strains, clinicians have no authorized therapeutic mAb for treatment. It raises a huge concern, especially for millions of immunocompromised patients. Since they do not adequately respond to COVID-19 vaccines, there is an urgent need to develop active mAbs for clinical use.

Most importantly, the current study highlighted how challenging it would be to anticipate the SARS-CoV-2 antigenic trajectory. Nonetheless, the development of next-generation COVID-19 vaccines and mAb therapies will have to keep that into consideration to design products offering broader protection against ever-evolving SARS-CoV-2.

Journal reference: Wang, Q., Iketani, S., Li, Z., Liu, L., Guo, Y., Huang, Y., Bowen, A.D., Liu, M., Wang, M., Yu, J., Valdez, R., Lauring, A.S., Sheng, Z., Wang, H.H., Gordon, A., Liu, L., Ho, D.D., (2023). Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. Cell. doi: https://doi.org/10.1016/j.cell.2022.12.018 https://www.cell.com/cell/fulltext/S0092-8674(22)01531-8




https://www.news-medical.net/news/20221216/SARS-CoV-2-Omicron-BQ-and-XBB-subvariants-show-exceptional-immune-evasion-properties.aspx#amp_tf=From%20%251%24s&aoh=16713971600235&csi=0&referrer=https%3A%2F%2Fwww.google.com&share=https%3A%2F%2Fwww.news-medical.net%2Fnews%2F20221216%2FSARS-CoV-2-Omicron-BQ-and-XBB-subvariants-show-exceptional-immune-evasion-properties.aspx

The skin has a remarkable capacity to regenerate itself after injury. This complicated process starts with inflammation and ends with the formation of new skin and scar tissue.

But wounds can get infected. And some diseases and conditions, such as diabetes and immunosuppression, may interfere with wound healing. Nonhealing wounds can lead to pain, loss of functioning, and even amputation or death. More than 6 million people in the U.S. alone are living with a chronic, nonhealing wound.

An NIH-funded research team at Stanford University led by Drs. Geoffrey Gurtner and Zhenan Bao has been testing technologies to encourage wound healing. In a new study, they designed a smart bandage to actively assist the healing process. They described their results on November 24, 2022, in Nature Biotechnology.

The smart bandage consists of an extremely thin, flexible printed circuit. A small, coiled antenna draws power wirelessly from a nearby source. This allows the bandage to provide electrical stimulation to injured tissue. Such stimulation has been shown to boost wound healing.

The wireless power also allows the bandage to monitor the skin underneath for signs of healing or infection. It does this by measuring temperature and how easily an electrical current passes through the area.

To stick the bandage to the skin, the researchers developed an adhesive gel that loosens when heated above body temperature. This allows it to be removed without causing damage to vulnerable skin. At normal skin temperature, the gel proved to be as sticky as a standard medical tape.

Healthy mice wearing the bandage moved normally, and the bandage was able to capture information about their skin during movement. No skin irritation was observed over a period of about two weeks.

Skin wounds on mice treated with electrical stimulation provided by the smart bandage healed about 25% more quickly than those covered with a standard sterile dressing. The new skin on the mice who got the smart bandage showed an increase in new blood vessels. It was also thicker and stronger than that on mice given standard bandages. Similar results were seen in mouse models of burn healing and diabatic wounds.

When the researchers examined cells from mice given the smart bandage, they found that certain types of immune cells had increased activity of genes involved in tissue regeneration. This was accompanied by increases in the corresponding proteins needed for healing processes.

“With stimulation and sensing in one device, the smart bandage speeds healing, but it also keeps track as the wound is improving,” explains Dr. Artem Trotsyuk, who helped lead the study.

“It is an active healing device that could transform the standard of care in the treatment of chronic wounds,” adds Dr. Yuanwen Jiang, who also helped lead the study.

Before the proof-of-concept bandage can be tested in people, several steps need to be taken. These include enlarging it to a human-sized version and testing it on larger animals before beginning human trials.

—by Sharon Reynolds




https://www.nih.gov/news-events/nih-research-matters/smart-bandage-improves-wound-healing-mice

Bhavana Kunkalikar By Bhavana KunkalikarDec 13 2022 Reviewed by Danielle Ellis, B.Sc. In a recent study posted to the bioRxiv* preprint server, researchers assessed the association of enhanced migratory or activated CD8+ T cell and reduced avidity reactive cellular response due to post-acute coronavirus disease 2019 (COVID-19) syndrome (PASC).

Study: Increased migratory/activated CD8+ T cell and low avidity SARS-CoV-2 reactive cellular response in post-acute COVID-19 syndrome. Image Credit: Kateryna Kon/Shutterstock Study: Increased migratory/activated CD8+ T cell and low avidity SARS-CoV-2 reactive cellular response in post-acute COVID-19 syndrome. Image Credit: Kateryna Kon/Shutterstock Background Post-infectious Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is sufficiently documented as a consequence of a number of illnesses, predominantly viral infections such as COVID-19. PASC manifests as a chronic multisystemic disease with several respiratory, cardiovascular, gastrointestinal, and neurological characteristics.

Emerging epidemiologic research highlights concentration difficulties, post-traumatic stress disorder (PTSD), as well as sleep disorders among psychiatric or neurological complications post-COVID-19. However, there is currently no data on the immunological pathogenesis of PASC that affects a considerable fraction of the general population.

About the study The present study investigated the immunological response in 40 COVID-19 patients with non-specific PASC and 15 healthy COVID-19 convalescent donors.

The team utilized peripheral blood mononuclear cells (PBMCs) and serological samples obtained from 40 convalescent COVID-19 patients diagnosed with PASC and 15 convalescent patients who did not exhibit any PASC symptoms. Cognitive, psychiatric impairment, or symptomatic characteristics were predicated on psychiatrically pertinent ICD 10 diagnosis. Characterization of activation or migration status of T cells, assessment of SARS-CoV-2 reactive T cells, as well as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralization assay were conducted.

To evaluate the activation and migratory status of peripheral T cells, the team evaluated three G protein-coupled receptors essential for autoimmunity and inflammation, namely the chemokine receptors called CXCR3, CCR5, and EBI2.

Results The study group consisted of individuals who tested SARS-CoV-2 negative via nasal swab testing at the time of enrolment. During the acute period of COVID-19, 96% and 100% of the PASC and control cohorts exhibited moderate COVID-19 severity without needing hospitalization, while 4% were seriously or critically ill and were hospitalized, respectively.

Related Stories What is the relation between COVID-19 vaccination and new POTS-related diagnoses? Study shows emerging Omicron sublineages efficiently evade neutralization independent of immunization history Research reveals that a viral toxin may contribute to the severity of COVID-19 During enrolment, the median COVID-19 convalescence duration for the PASC and the control cohorts was 10 and eight months, respectively. All subjects in the control group and 82.5% of those in the PASC group had received a minimum of two COVID-19 messenger ribonucleic acid (mRNA) vaccinations. The PASC and study group's median age was 51.5 years, while the median age of the control group was 30 years. The PASC and the control groups were composed of 63% and 70% women, respectively, and there was no statistically significant difference between the sexes. Patients with PASC had a considerably greater body mass index (BMI) than controls.

The frequency of CD4+ and CD8+ T lymphocytes was comparable between the two study cohorts. Compared to the control cohort, the PASC group had a considerably higher number of CD4+ T cells that expressed CCR5, CD8+ T cells that expressed CXCR3, and CD8+ and CD4+ T cells that expressed EB12, as well as a higher number of CD4+CXCR3+ T cells. However, these differences in frequencies did not reach statistical significance. PASC and the control groups had comparable frequencies of CD8+CCR5+ T cells.

Furthermore, PASC patients had a significantly increased frequency of CD4+ and CD8+ T cells that co-expressed CCR5 and CXCR3, as well as CD4+ T cells that co-expressed EB12 and CCR5 in comparison to the control subjects.

The frequency of SARS-CoV-2 wild-type (WT)- and Alpha variant-reactive CD4+ T cells, designated as CD154+CD137+, was comparable across the PASC and the control cohorts. The frequencies of SARS-CoV-2-reactive CD4+ T cells expressing interleukin (IL)-2, tumor necrosis factor (TNF)-alpha, and granzyme B (GrB), were comparable between the two groups, with the exception of IFN-producing WT-reactive CD4+ T cells, which were considerably more prevalent in PASC patients.

The team also observed comparable numbers of reactive CD4+ and CD8+CD3, indicating that the two groups can achieve a similar maximal functional avidity status with respect to reactive T cell populations. Yet, the assessment of the CD3-high categories revealed significantly greater frequencies of WT- and alpha-reactive CD8+CD3 high T cells in the PASC group, indicating the presence of a reactive but low-avidity with a possibly uncoordinated-CD8 T cell response in PASC patients.

Conclusion Overall, the study findings suggested that the genesis of non-specific PASC may stem from an inflammatory response produced by a high but low avidity pro-inflammatory CD8+ T cell response against COVID-19, as well as the production of circulating autoantibodies. The researchers believe these findings could have consequences for future therapeutic techniques and public health initiatives.

*Important notice bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference: Paniskaki, K. et al. (2022) Increased migratory/activated CD8+ T cell and low avidity SARS-CoV-2 reactive cellular response in post-acute COVID-19 syndrome. bioRxiv. doi: 10.1101/2022.12.03.519007. https://www.biorxiv.org/content/10.1101/2022.12.03.519007v1 https://www.biorxiv.org/content/10.1101/2022.12.03.519007v1




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TOPICS:CancerCoffeeDiabetesNutritionParkinson's DiseasePopular By SCITECHDAILY.COM DECEMBER 9, 2022

Morning Coffee Happy

The great flavor of your favorite beverage may be enough to persuade you to continue drinking it. However, it can’t hurt to recognize that you also benefit from these eight health-inducing perks. Your daily cups of coffee can help you live longer. They might also stave off several severe illnesses and improve your functioning.

Longevity

Studies show drinking coffee can prolong lifespan. Over 10 years, researchers looked at the connection between coffee consumption and death risk. Scientists considered variables like the participants’ lifestyles, wellness, and coffee consumption.

The research revealed that people who drank over four cups of coffee daily enjoyed a 64% death risk reduction compared to non-coffee-drinking participants and those who drank only a little. In the follow-up period, coffee drinkers aged 45 or above benefitted from a 30% reduction in death risk.

Brain Function

Coffee contains a psychoactive substance that blocks the neurotransmitter adenosine in the brain. Consequently, other neurotransmitters like norepinephrine and dopamine increase along with neural firing. Cognitive functioning improves when you drink coffee, along with vigilance, memory, reaction speed, productivity, and motivation.

Pouring Coffee Cup Various studies have demonstrated that drinking coffee can prolong lifespan.

Physical functioning

The caffeine in coffee prepares your body for intense exertion, releasing fat cells for activity and increasing adrenaline, and it can boost physical performance by 12%.

Ramp up metabolism

Caffeine helps people burn fat and is often a key ingredient in weight loss products. Studies show it can increase fat loss by 29% and boost metabolism by 11% in trim people and 10% in obese individuals.

Nutrients

Coffee contains vital nutrients, including riboflavin, niacin, magnesium, potassium, manganese, and pantothenic acid. The amounts are small, but your intake increases with each cup of coffee.

Happy Coffee Smile Studies have shown that people who drink coffee are less likely to suffer from senile dementia and Alzheimer’s disease.

Brain protection

Coffee drinking may help you avoid age-related cognitive decline. No cure exists for getting old, but you can consider your coffee habit helpful for brain maintenance. Researchers conclude coffee drinkers are 65% less likely to suffer from senile dementia and Alzheimer’s disease than non-coffee drinkers.

Liver health

Four mugs of coffee can potentially reduce cirrhosis of the liver risk by 80%. Cirrhosis causes scar tissue to build, replacing part of the liver, and is associated with hepatitis and fatty liver disease.

Lower risk of cancer, Parkinson’s disease, and diabetes

Research shows you are less likely to develop type 2 diabetes as a coffee drinker. Each cup lowers the risk by 7%. Frequent caffeinated coffee consumption can lessen the risk of liver and colorectal cancer. It also reduces the risk of Parkinson’s disease by up to 60%.

Now you know your daily cups of coffee have more to offer than their terrific taste. You could see improved physical and mental wellness and lower chances of developing diseases if you continue your habit.

References:

WebMD, “Drink Coffee, Live Longer?” Healthline.com. Medalerthelp.org/news/coffee-consumption-may-reduce-the-risk-of-alzheimers/.




https://scitechdaily.com/top-8-health-benefits-of-drinking-coffee/

At a Glance A vaccine using mRNA technology induced an immune response in mice and ferrets against 20 different types of influenza. It also provided the animals protection against death from flu strains not included in the vaccine, showing its potential to help prevent future flu pandemics. Colorized electron micrograph of three round virus particles Influenza virus particles isolated from a patient sample and propagated in cell culture. John Gallagher and Audray Harris, NIAID Laboratory of Infectious Diseases Influenza, the virus that causes the flu, can be deadly. Twenty different types of the virus have been identified. Many of these circulate between animals and people. This, along with the seasonal virus’s frequent mutations, makes developing effective flu vaccines with broad protection difficult.

Seasonal flu vaccines are reformulated each year to tailor them to the virus types predicted to be most common in the upcoming flu season. If these predictions are off, the season’s flu vaccine may not provide optimal protection.

Researchers have long been working toward a universal vaccine that could protect against all known influenza types and prevent future flu pandemics. Most of these efforts have focused on trying to induce the immune system to recognize areas of the virus that are similar between types.

An NIH-funded research team led by Dr. Scott Hensley from the University of Pennsylvania tested a different strategy. They designed a vaccine that included a virus protein from all 20 distinct influenza types. Such a strategy hadn’t been possible with traditional vaccine production methods. But the researchers thought it might be with mRNA technology. This technology had been used for some of the vaccines against SARS-CoV-2, the virus that causes COVID-19.

In their new study, the team made a vaccine using mRNAs for a key virus protein called hemagglutinin (HA) from all 20 influenza types. The mRNA was packaged in protective fatty nanoparticles. The researchers then tested the vaccine in mice and ferrets. Results were published on November 25, 2022, in Science.

Vaccinated mice produced antibodies against both similar and unique regions of all 20 different HAs, and levels of these antibodies remained unchanged for months after vaccination. This robust antibody production occurred whether or not the mice had previously been exposed to one of the flu strains.

When vaccinated mice were exposed to a flu strain similar to one of those in the vaccine, they stayed relatively healthy, and all survived the viral challenge. In contrast, unvaccinated mice exposed to the same flu strain did not survive.

When the team exposed vaccinated mice to a flu strain that was less similar to the ones in the vaccine, the mice got sick but recovered faster than unvaccinated mice. Most of the vaccinated mice survived, but none of the unvaccinated mice did. Even when the researchers depleted T cells, which can also help protect again infection, from the vaccinated mice, the vaccine remained effective. This result showed that most of the protection was coming from the vaccine-generated antibodies.

Finally, the researchers tested a two-dose vaccination strategy, similar to that used for COVID-19, in ferrets. A month after the second dose, they challenged the ferrets with an avian flu strain that was distinct from the ones used in the vaccine. Vaccinated animals got sick, but recovered quickly and all survived. In contrast, half of the unvaccinated animals died, and those that survived took longer to clear the virus from their bodies.

“For a conventional vaccine, immunizing against all these types would be a major challenge, but with mRNA technology it’s relatively easy,” Hensley says. “The idea here is to have a vaccine that will give people a baseline level of immune memory to diverse flu strains, so that there will be far less disease and death when the next flu pandemic occurs.”

This vaccine hasn’t yet been tested in people. But with further development, such universal mRNA vaccines have the potential to protect against both seasonal influenza viruses and those with the potential to cause pandemics.

—by Sharon Reynolds




https://www.nih.gov/news-events/nih-research-matters/using-mrna-technology-universal-flu-vaccine

Reviewed by Emily Henderson, B.Sc.Dec 13 2022 Vitamin D plays an important role in the regulation of calcium and phosphorus absorption by the organism. It also helps keep the brain and immune system working. Researchers at the Federal University of São Carlos (UFSCar) in Brazil and University College London (UCL) in the United Kingdom have now shown that vitamin D supplementation reduces the risk of dynapenia in older people by 78%.

Dynapenia is an age-associated loss of muscle strength. It can be partially explained by muscle atrophy and is a major risk factor for physical incapacity later in life. People with dynapenia are more likely to fall, need to go to hospital, be prematurely institutionalized, and die.

An article on the study is published in the journal Calcified Tissue International and Musculoskeletal Research. The study was supported by FAPESP.

The researchers analyzed data for 3,205 non-dynapenic individuals aged 50 and over who were followed for four years by the English Longitudinal Study of Ageing (ELSA), a long-term multi-cohort study that began in 2002 and has had more than 15 years of follow-up.

Vitamin D is known to participate in various functions of the organism. Actually, it's a hormone and its many roles include helping to repair muscles and releasing calcium for muscle contraction kinetics. It was therefore expected to cause muscle alterations of some kind. That's exactly what our study proved.

Tiago da Silva Alexandre, last author of the article

Alexandre is a professor of gerontology at UFSCar.

Bone and muscle tissue are interconnected not just mechanically and physically but also biochemically. Endocrine disorders such as vitamin D deficiency or insufficiency can lead to loss of bone mineral density as well as a reduction in muscle mass, strength and function, he said.

The study sample comprised individuals aged 50 and over without dynapenia. Grip strength (considered a good proxy for overall muscle strength) was 26 kg or more for men and 16 kg or more for women.

The main conclusion was that individuals with vitamin D deficiency, defined as less than 30 nanomoles per liter in the blood, had a 70% higher risk of developing dynapenia by the end of the four-year study period than those with normal levels of vitamin D, defined as more than 50 nmol/L.

Related Stories Does vitamin D reduce COVID-19 severity? Boosting vitamin D levels not associated with protection against respiratory tract infections or covid-19 Severe vitamin D deficiency associated with greater risk of premature mortality This is itself an important finding as it shows that vitamin D deficiency heightens the risk of muscle weakness by 70%. However, because we knew there are many worldwide cases of people with osteoporosis who take vitamin supplements, we needed to try to measure the effectiveness of vitamin D supplementation, said Maicon Luís Bicigo Delinocente, first author of the article. He was supported by a scholarship from FAPESP.

When individuals with osteoporosis and those taking vitamin D were excluded from the analysis, he explained, we found that the risk of developing muscle weakness by the end of the four-year period was 78% higher for subjects with vitamin D deficiency at the start of the study than for subjects with normal vitamin D levels and 77% higher for those with vitamin D insufficiency [30-50 nmol/L].

The results proved that the risk of muscle weakness is heightened by both vitamin D deficiency and insufficiency, Alexandre said. Another conclusion to be derived from the results of the study is that it's important to take vitamin D if you have a deficiency or insufficiency, he added. The study analyzed data for people who live in the UK. There are many more days of sunlight per year in Brazil, and yet we're known to have a high incidence of vitamin D deficiency and insufficiency, especially among older people. Indeed, this is the case worldwide.

Our body only synthesizes vitamin D when large areas of skin are exposed to sunlight, Alexandre recalled. It's necessary to explain to people that they risk losing muscle strength if they don't get enough vitamin D. They need to expose themselves to the sun, eat food rich in vitamin D or take a supplement, and do resistance training exercises to maintain muscle strength, he said.

Source: São Paulo Research Foundation (FAPESP)

Journal reference: Delinocente, M.L.B., et al. (2022) Are Serum 25-Hydroxyvitamin D Deficiency and Insufficiency Risk Factors for the Incidence of Dynapenia?. Calcified Tissue International. doi.org/10.1007/s00223-022-01021-8.




https://www.news-medical.net/news/20221213/Vitamin-D-supplements-reduce-the-risk-of-dynapenia-in-older-people-by-7825.aspx#amp_tf=From%20%251%24s&aoh=16713045087784&csi=0&referrer=https%3A%2F%2Fwww.google.com&share=https%3A%2F%2Fwww.news-medical.net%2Fnews%2F20221213%2FVitamin-D-supplements-reduce-the-risk-of-dynapenia-in-older-people-by-7825.aspx

December 15, 20225:00 AM ET NPR STAFF

Households can order four free COVID tests on COVIDtests.gov starting on Thursday. They'll begin shipping by mail next week. Justin Sullivan/Getty Images Americans can order four more free COVID-19 tests through the mail, starting on Thursday. It's part of the Biden administration's plan to deal with an increase in COVID cases sparked by indoor holiday gatherings.

The tests can be ordered on COVIDtests.gov and will start to ship the week of Dec. 19, a senior administration official told reporters on a conference call. The government is urging people to test themselves when they have symptoms, and before visiting with family.

It's the fourth round of free rapid tests this year. The White House had suspended the program in September and said that it would not be able to send out more kits because Congress denied requests for more funding for the program. But the administration shuffled around funds to buy more of the tests for the national stockpile, the official said.

Experts are concerned Thanksgiving gatherings could accelerate a 'tripledemic' SHOTS - HEALTH NEWS Experts are concerned Thanksgiving gatherings could accelerate a 'tripledemic' White House asks for $47 billion for Ukraine, COVID-19, monkeypox and disasters POLITICS White House asks for $47 billion for Ukraine, COVID-19, monkeypox and disasters We know that the virus will circulate more quickly and easily as folks gather indoors for the winter holiday season, the official said, speaking on condition of anonymity. Officials saw cases increase after Thanksgiving, and anticipate that there could be another uptick after December holiday celebrations.

Tests are also available at community testing sites, food banks and schools, and through Medicare. People covered by private health insurance plans can get fully reimbursed for eight tests per month.

The federal government is trying to make it easier for Americans to get vaccines, tests and COVID treatments like Paxlovid during the winter months. It is staging supplies like ventilators as well as personal protective equipment, and wants to help states set up mobile and pop-up vaccination sites.

Sponsor Message

The government has a particular focus on nursing homes and long-term care facilities, and wants to work to vaccinate residents with the latest booster shot, and offer Paxlovid to people who get the virus.

We are a few years into this pandemic, and we are prepared for this moment, the official said.




https://www.npr.org/2022/12/15/1142926180/free-covid-tests-mail-order

Reviewed by Emily Henderson, B.Sc.Dec 15 2022 COVID-19 vaccinations that combine two or more distinct variants of the SARS-CoV-2 virus could offer protection against both current and future 'variants of concern', say scientists at the University of Cambridge and Medical University of Innsbruck.

In research published in Nature Communications, scientists show that the omicron variant of the virus is immunologically distinct from other variants such as the vaccine variant and the alpha and delta variants - that is, exposure to it has a different effect on the neutralising antibody response and hence protection to other variants. But also, sub-variants of omicron are themselves distinct from each other. Their research further suggests that a combination of infection plus vaccination could provide increased protection against future variants.

Since SARS-CoV-2 was first identified in 2020, new variants of the virus have emerged as its genetic code evolves. Some of these variants threaten to spread faster, be more virulent or evade the protection of the vaccine - these are known as 'variants of concern'.

Antonia Netzl, a PhD student at Trinity Hall, Cambridge, together with colleagues at Cambridge and Innsbruck, analysed data on people's immune responses to different variants and vaccinations. They used these to create 'antigenic maps' and 'antibody landscapes' to explore the differences between variants.

A more recent variant of concern is the omicron variant, but since its emergence in December 2021 several sub-lineages have evolved, including BA.1, BA.2, BA.4, BA.5, and BA.2.12.1. Of these, BA.5 became the dominant variant in many countries earlier this year, though new dominant variants have subsequently supplanted it.

Netzl and colleagues found, using their maps, that not only was omicron immunologically distinct from alpha and delta, but its sub-variants BA.1, BA.2 and BA.5 were also distinct from each other. The antibody landscapes, an illustration of people's immune profile, allowed the researchers to see how vaccination and/or infection with another variant increased virus neutralization against other viruses.

We found that people who had been exposed to BA.1 were better protected against BA.2, but the reverse wasn't true.

But the good news was that we also found that two distinct exposures - for example, vaccination plus infection with a different variant - increased antibody levels against all variants. So, people who had been vaccinated and then infected with delta, for example, were better protected against omicron than those who had only been vaccinated or infected and not both.

Antonia Netzl, a Gates Cambridge Scholar

Drug Discovery eBook Drug Discovery Industry Focus eBook Compilation of the top interviews, articles, and news in the last year. Download a free copy Netzl says this suggests that an update of the vaccine variant will be beneficial for increasing antibody levels and thereby offering some protection against all currently circulating variants as well as yet-unknown variants.

Our work suggests that an update of the vaccine variant will be beneficial for increasing antibody levels and thereby protection against all currently circulating variants. The bivalent vaccines, which contain the original prototype variant and an omicron variant in a single vaccine dose, could provide this increased protection.

The findings are supported by clinical trials and have already been put into practice with the roll-out of the bivalent Prototype+omicron BA.4/5 and Prototype+omicron BA.1 vaccines.

Although infection by multiple different variants gives the unvaccinated protection too, Netzl points out that vaccinations offer effective protection and reduce the severity of infection.

People should still make sure they get themselves vaccinated, even if they have already had COVID once. Vaccination is important for boosting our immune response and thereby reducing the risk of infection and symptom severity.

Netzl said the research, alongside the real-world clinical trials, gives a strong basis to the investigations in vaccine development and design.

This research was carried out at the University of Cambridge and the Janine Kimpel Group at the University of Innsbruck. The co-lead authors were Antonia Netzl and Annika Rössler.

Source: University of Cambridge

Journal reference: Rössler, A., et al. (2022) BA.2 and BA.5 omicron differ immunologically from both BA.1 omicron and pre-omicron variants. Nature Communications. doi.org/10.1038/s41467-022-35312-3.




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