Fat burning during exercise varies widely between individuals

 The best heart rate for burning fat differs for each individual and often does not align with the "fat burning zone" on commercial exercise machines, Icahn School of Medicine at Mount Sinai researchers report.

Instead, the researchers said, clinical exercise testing—a diagnostic procedure to measure a person's physiological response to exercise—may be a more useful tool to help individuals achieve intended fat loss goals. The study, which used a machine learning-based modeling approach, was published online in Nutrition, Metabolism and Cardiovascular Disease. The paper is titled, "Discrepancy between predicted and measured exercise intensity for eliciting the maximal rate of lipid oxidation."

"People with a goal of weight or fat loss may be interested in exercising at the intensity which allows for the maximal rate of fat burning. Most commercial exercise machines offer a 'fat-burning zone' option, depending upon age, sex, and heart rate," says lead author Hannah Kittrell, Ph.D. candidate at Icahn Mount Sinai in the Augmented Intelligence in Medicine and Science laboratory. "However, the typically recommended fat-burning zone has not been validated, thus individuals may be exercising at intensities that are not aligned with their personalized weight loss goals."

The term FATmax is sometimes used to represent the exercise intensity and associated heart rate at which the body reaches its highest fat-burning rate during aerobic exercise. At this point, fat is a significant fuel source and therefore this intensity may be of interest to those seeking to optimize fat loss during workouts.

As part of the study, the researchers compared heart rate at FATmax, as measured during a clinical exercise test, to predicted heart rate at percentages of maximal effort within the typically recommended "fat-burning zone."

In a sample of 26 individuals, the researchers found that there was poor agreement between measured and predicted heart rate, with a mean difference of 23 beats per minute between the two measures. This suggests that general recommendations for a "fat-burning zone" may not provide accurate guidance.

Next, the researchers plan to study whether individuals who receive a more personalized exercise prescription demonstrate more weight and fat loss, as well as improvement of metabolic health markers that identify health risks like type 2 diabetes, obesity, and heart disease.

More information: Hannah D. Kittrell et al, Discrepancy between predicted and measured exercise intensity for eliciting the maximal rate of lipid oxidation, Nutrition, Metabolism and Cardiovascular Diseases (2023). DOI: 10.1016/j.numecd.2023.07.014

https://medicalxpress.com/news/2023-08-fat-varies-widely-individuals.html

Global study finds COVID-19 disease may cause change in menstrual cycle length

 A new international study finds that individuals with COVID-19 disease may experience small, temporary changes in menstrual cycle length. Researchers emphasize changes are minor and typically return to normal in next menstrual cycle.

The study, published today in the journal Obstetrics & Gynecology, was an international collaborative effort led in part by Oregon Health & Science University reproductive health services researcher Blair Darney, Ph.D., M.P.H.; physician-scientist Alison Edelman, M.D., M.P.H.; and Alexandra Alvergne, Ph.D., of the University of Montpellier.

Their findings build on prior work from the same research team that first identified an association between COVID-19 vaccines and menstrual cycle changes. However, existing literature on the effects of COVID-19 disease itself on the menstrual cycle is limited. This study aimed to identify these effects, as well compare any changes to those seen with COVID-19 vaccination.

"As the prevalence of COVID-19 has increased, the public has reported a range of menstrual cycle changes, including longer length of cycle. Knowing this was a widespread concern, our team—along with other reproductive health experts across the globe—made this research a top priority," said Edelman, a professor of obstetrics and gynecology in the OHSU School of Medicine.

"Menstrual health is significantly understudied and underrepresented in research and medicine. This work is important and necessary to provide answers that can reassure individuals who are experiencing menstrual changes following a COVID-19 infection."

In the retrospective cohort study, researchers analyzed menstrual cycle data from more than 6,000 individuals in 110 countries using Clue, a menstrual and reproductive health platform.

"We are proud to contribute to such important research on the effects of COVID-19 on the menstrual cycle and to work closely with world-class researchers at Oregon Health & Science University and the University of Montpellier," said Amanda Shea, Ph.D., head of science at Clue.

"This research underlines the power of Clue's de-identified user data and its impact in advancing research into menstrual cycles and reproductive health; benefitting society via a more accurate understanding of reproductive health."

Among unvaccinated participants reporting COVID-19 illness, researchers found, on average, a 1.45-day increase in menstrual cycle length compared with participants' previous cycle length average. These increases were consistent with changes reported among the cohort who had received a COVID-19 vaccination.

Researchers emphasize that in both cohorts, changes resolved in the first cycle after vaccination or illness. Additionally, they note that the immune and reproductive systems are known to interact with each other, so while these findings aren't surprising, they should validate the public's experiences and provide reassurance that if changes in flow occur during or after COVID-19 infection, they are likely to be small and temporary.

"Changes to your menstrual cycle can be concerning and even frightening," said Darney, an associate professor of obstetrics and gynecology in the OHSU School of Medicine. "We want this research to reassure individuals that on a population level, these changes are not typically a cause for concern."

Cycle changes are likely due to temporary, disease-related activation of immune response, but because individuals naturally experience variations in menstrual cycle duration and bleeding patterns, researchers say that it is challenging to isolate COVID-19 as a sole cause. The research team also notes that the study was not focused on individuals known to be experiencing long COVID-19. The physician-scientists also advise that individuals who notice prolonged changes in menstruation should seek guidance from their clinician.

Looking forward, researchers hope to learn more about the biological mechanism of these changes and will continue to leverage data from cycle tracking apps to investigate other reported variations in menstruation following vaccination, including missed cycles, unexpected vaginal bleeding and pain.

More information: Alexandra Alvergne et al, Associations Among Menstrual Cycle Length, Coronavirus Disease 2019 (COVID-19), and Vaccination, Obstetrics & Gynecology (2023). DOI: 10.1097/AOG.0000000000005343

https://medicalxpress.com/news/2023-08-global-covid-disease-menstrual-length.html

Social media use interventions alleviate symptoms of depression

 Receiving therapy for problematic social media use can be effective in improving the mental well-being of people with depression, finds a new study by University College London researchers.

The research, published in the Journal of Medical Internet Research, found that social media use interventions could help adults for whom social media use has become problematic or interferes with their mental health.

Problematic use is when a person's preoccupation with social media results in a distraction from their primary tasks and the neglect of responsibilities in other aspects of their life.

Previous research has suggested that social media use can become problematic when it starts to interfere with a person's daily life and leads to poor mental well-being, including depression, anxiety, stress and loneliness.

To address these issues, and improve users' mental health, social media use interventions have been developed and evaluated by researchers. Such techniques include abstaining from or limiting use of social media, alongside therapy-based techniques such as Cognitive Behavioral Therapy (CBT).

The researchers analyzed 23 studies which featured participants from across the globe, between 2004 and 2022. They found that in more than a third of studies (39%), social media use interventions improved mental well-being.

Improvements were particularly notable in depression (low mood), as 70% of studies saw a significant improvement in depression following the intervention.

Therapy-based interventions were most effective—improving mental well-being in 83% of studies, compared to a 20% of studies finding an improvement where social media use was limited and 25% where social media was given up entirely.

Lead author, Dr. Ruth Plackett (UCL Institute of Epidemiology & Health), said, "Mental health issues are on the rise, as is the number of people who use social media.

"Health and care professionals should be aware that reducing time spent on social media is unlikely to benefit mental well-being on its own.

"Instead, taking a more therapy-based approach and reflecting on how and why we are interacting with social media and managing those behaviors could help improve mental health."

Study author and GP Dr. Patricia Schartau (UCL Institute of Epidemiology & Health), added, "As primary care physicians, we should proactively explore social media use and its effects on mental health in patients who present with anxiety and/or low mood in order to give those patients the opportunity to benefit from treatment including some of the more effective interventions outlined in our review."

In 2022 it was estimated that 4.59 billion people globally used at least one form of social media and the sites have dramatically changed how people communicate, form relationships and perceive each other.

While some studies report that social media can be beneficial to users and provide them with increased social support, other evidence links social media with depression, anxiety and other psychological problems—particularly in young people.

The researchers hope that their findings will help to develop guidance and recommendations for policymakers and clinicians on how best to manage problematic social media use.

However, further research is needed in order to investigate who may benefit most from social media use interventions.

Study limitations

Current experimental research is of low quality, with issues of selection bias making it difficult to generalize the findings.

Further experimental and longitudinal research is needed with representative samples to investigate who may benefit most from social media use interventions.

More information: The impact of social media use interventions on mental well-being: a systematic review, Journal of Medical Internet Research (2023).

https://medicalxpress.com/news/2023-08-social-media-interventions-alleviate-symptoms.html

Harnessing the body's own immune cells to fight brain cancer

 Glioblastoma, the most common and deadly form of brain cancer, grows rapidly to invade and destroy healthy brain tissue. The tumor sends out cancerous tendrils into the brain that make surgical tumor removal extremely difficult or impossible.

Now, Salk scientists have found the immunotherapy treatment anti-CTLA-4 leads to considerably greater survival of mice with glioblastoma. Furthermore, they discovered that this therapy was dependent on immune cells called CD4+ T cells infiltrating the brain and triggering the tumor-destructive activities of other immune cells called microglia, which permanently reside in the brain.

Published in Immunity on August 11, 2023, the findings show the benefit of harnessing the body's own immune cells to fight brain cancer and could lead to more effective immunotherapies for treating brain cancer in humans.

"There are currently no effective treatments for glioblastoma—a diagnosis today is basically a death sentence," says Professor Susan Kaech, senior author and director of the NOMIS Center for Immunobiology and Microbial Pathogenesis. "We're extremely excited to find an immunotherapy regimen that uses the mouse's own immune cells to fight the brain cancer and leads to considerable shrinkage, and in some cases elimination, of the tumor."

When standard cancer treatments like surgery, chemotherapy, and radiation cease to be effective, doctors increasingly turn to immunotherapy, which encourages the body's own immune cells to seek and destroy cancer cells. Though not universal, immunotherapy works on many tumors and has provided many patients with strong, long lasting anti-cancer responses. Kaech wanted to find new ways of harnessing the immune system to develop more safe and durable treatments for brain cancer.

Her team found three cancer-fighting tools that have been somewhat overlooked in brain cancer research that may cooperate and effectively attack glioblastoma: an immunotherapy drug called anti-CTLA-4 and specialized immune cells called CD4+ T cells and microglia.

Anti-CTLA-4 immunotherapy works by blocking cells from making the CTLA-4 protein, which, if not blocked, inhibits T cell activity. It was the first immunotherapy drug designed to stimulate our immune system to fight cancer, but it was quickly followed by another, anti-PD-1, that was less toxic and became more widely used.

Whether anti-CTLA-4 is an effective treatment for glioblastoma remains unknown since anti-PD-1 took precedence in clinical trials. Unfortunately, anti-PD-1 was found to be ineffective in multiple clinical trials for glioblastoma—a failure that inspired Kaech to see whether anti-CTLA-4 would be any different.

As for the specialized immune cells, CD4+ T cells are often overlooked in cancer research in favor of a similar immune cell, the CD8+ T cell, because CD8+ T cells are known to directly kill cancer cells. Microglia live in the brain full time, where they patrol for invaders and respond to damage—whether they play any role in tumor death was not clear.

First, the researchers compared the life spans of mice with glioblastoma when treated with anti-CTLA-4 versus anti-PD-1. After discovering that blocking CTLA-4 prolonged their life spans considerably, but blocking PD-1 did not, the team moved on to figure out what made that outcome possible.

They found that after anti-CTLA-4 treatment, CD4+ T cells secreted a protein called interferon gamma that caused the tumor to throw up "stress flags" while simultaneously alerting microglia to start eating up those stressed tumor cells. As they gobbled up the tumor cells, the microglia would present scraps of tumor on their surface to keep the CD4+ T cells attentive and producing more interferon gamma—creating a cycle that repeats until the tumor is destroyed.

"Our study demonstrates the promise of anti-CTLA-4 and outlines a novel process where CD4+ T cells and other brain-resident immune cells team up to kill cancerous cells," says co-first author Dan Chen, a postdoctoral researcher in Kaech's lab.

To understand the role of microglia in this cycle, the researchers collaborated with co-author and Salk Professor Greg Lemke, holder of the Françoise Gilot-Salk Chair. For decades, Lemke has investigated critical molecules, called TAM receptors, used by microglia to send and receive crucial messages. The researchers found that TAM receptors told microglia to gobble up cancer cells in this novel cycle.

"We were stunned by this novel codependency between microglia and CD4+ T cells," says co-first author Siva Karthik Varanasi, a postdoctoral researcher in Kaech's lab. "We are already excited about so many new biological questions and therapeutic solutions that could radically change treatment for deadly cancers like glioblastoma."

Connecting the pieces of this cancer-killing puzzle brings researchers closer than ever to understanding and treating glioblastoma.

"We can now reimagine glioblastoma treatment by trying to turn the local microglia that surround brain tumors into tumor killers," says Kaech, holder of the NOMIS Chair. "Developing a partnership between CD4+ T cells and microglia is creating a new type of productive immune response that we have not previously known about."

Next, the researchers will examine whether this cancer-killing cell cycle is present in human glioblastoma cases. Additionally, they aim to look at other animal models with differing glioblastoma subtypes, expanding their understanding of the disease and optimal treatments.

More information: Susan M. Kaech, CTLA-4 blockade induces a MHC-II+ microglia-Th1cell partnership that stimulates microglial phagocytosis and anti-tumor function in glioblastoma, Immunity (2023). DOI: 10.1016/j.immuni.2023.07.015. www.cell.com/immunity/fulltext … 1074-7613(23)00328-X

https://medicalxpress.com/news/2023-08-benefit-harnessing-body-immune-cells.html

Raising awareness of long COVID 'blue legs' symptom

 An unusual case of a long COVID patient's legs turning blue after 10 minutes of standing highlights the need for greater awareness of this symptom among people with the condition, according to new research. The study, "Venous insufficiency and acrocyanosis in long COVID: dysautonomia," has been published in The Lancet.

The paper, authored by Dr. Manoj Sivan at the University of Leeds, focuses on the case of one 33-year-old man who developed with acrocyanosis—venous pooling of blood in the legs.

A minute after standing, the patient's legs began to redden and became increasingly blue over time, with veins becoming more prominent. After 10 minutes the color was much more pronounced, with the patient describing a heavy, itchy sensation in his legs. His original color returned two minutes after he returned to a non-standing position.

The patient said he had started to experience the discoloration since his COVID-19 infection. He was diagnosed with postural orthostatic tachycardia syndrome (POTS), a condition that causes an abnormal increase in heart rate on standing.

Dr. Sivan, Associate Clinical Professor and Honorary Consultant in Rehabilitation Medicine in the University of Leeds' School of Medicine, said, "This was a striking case of acrocyanosis in a patient who had not experienced it before his COVID-19 infection.

"Patients experiencing this may not be aware that it can be a symptom of long COVID and dysautonomia and may feel concerned about what they are seeing. Similarly, clinicians may not be aware of the link between acrocyanosis and long COVID.

"We need to ensure that there is more awareness of dysautonomia in long COVID so that clinicians have the tools they need to manage patients appropriately."

Long COVID affects multiple systems in the body and has an array of symptoms, affecting patients' ability to perform daily activities. The condition also affects the autonomic nervous system, which is responsible for regulating blood pressure and heart rate.

Patient standing at two minutes. Credit: Use crediting University of Leeds

Acrocyanosis has previously been observed in children with dysfunction of the autonomic nervous system (dysautonomia), a common symptom of post-viral syndromes.

Previous research by Dr. Sivan's team has shown that both dysautonomia and POTS frequently develop in people with long COVID.

Patient standing at 10 minutes. Credit: Use crediting University of Leeds

Dysautonomia is also seen in a number of other long-term conditions such as fibromyalgia and myalgic encephalomyelitis, also known as chronic fatigue syndrome or ME.

Dr. Sivan said, "We need more awareness about dysautonomia in long term conditions; more effective assessment and management approaches, and further research into the syndrome. This will enable both patients and clinicians to better manage these conditions."

The research is the latest work by the team in the field of autonomic medicine. Other developments include a home test for people with symptoms of autonomic dysfunction in conditions such as long COVID, chronic fatigue syndrome, fibromyalgia, and diabetes 1 and 2, where people experience dizziness or blackouts.

More information: Venous insufficiency and acrocyanosis in long COVID: dysautonomia, The Lancet (2023).

https://medicalxpress.com/news/2023-08-awareness-covid-blue-legs-symptom.html

Pfizer, Scripps Sue to Block Copy of ‘Most Expensive’ Heart Drug

 Pfizer Inc. and the Scripps Research Institute allege in a new lawsuit that a copy of Vyndamax proposed by Dexcel Pharma Technologies Ltd. infringes three patents for the blockbuster heart drug, an increasingly important source of Pfizer’s revenue.

Pfizer and Scripps “together own all substantial rights” to the patents, according to a complaint filed Thursday in the US District Court for the District of Delaware. Two were assigned to Scripps and one to Pfizer.

Vyndamax is used to reduce the risk of death and hospitalization from a rare heart condition called transthyretin amyloid cardiomyopathy, or ATTR-CM. The disease is caused by a buildup of proteins in the heart.

The average survival time for untreated ATTR-CM patients ranges from 2.5 to 3.5 years, but studies have shown that patients who take tafamidis—Vyndamax’s active ingredient—tend to live nearly five years after diagnosis.

Dexcel didn’t immediately respond to a request for comment.

The drug has an annual wholesale cost of more than $240,000, Bloomberg Intelligence analyst Marc Engelsgjerd wrote in a note last October. In the wake of its May 2019 approval by the US Food and Drug Administration, researchers critical of its cost—then $225,000 a year—called Vyndamax “the most expensive cardiac medication in history” and said older adults were struggling to afford it.

Both of the Scripps patents—US Patent Nos. 7,214,695 and 7,214,696—cover methods of treating ATTR-CM using Vyndamax. The ’696 patent will expire in December 2023, followed by ’695 in April 2024, according to the entry for Vyndamax in the FDA’s registry of approved drugs, the Orange Book.

Pfizer’s US Patent No. 9,770,441, covering a crystalline form of tafamidis, will expire in August 2035. The three are the only Orange Book-listed patents for Vyndamax.

Vyndamax had US sales of $818 million during the first six months of 2023—46% higher than the $561 million it had in the same period in 2022, Pfizer said in its quarterly earnings report. The growth, Pfizer said, was “largely driven by continued strong uptake of the ATTR-CM indication, primarily in the US and developed Europe.”

Excluding revenue from Comirnaty and Paxlovid—Pfizer’s Covid-19 vaccine and antiviral pill, respectively—Vyndamax and its European and Japanese counterparts accounted for Pfizer’s fourth-highest revenue of any drug in 2022. The family of medicines together had sales of $2.45 billion last year, 2.4% of Pfizer’s revenue, according data compiled by Bloomberg LP. Of that, Vyndamax’s US sales were $1.25 billion.

Williams & Connolly LLP and Morris, Nichols, Arsht & Tunnell LLP represent Pfizer and Scripps.

The case is Pfizer Inc. v. Dexcel Pharma Techs. Ltd., D. Del., No. 23-cv-879, complaint filed 8/10/23.

https://news.bloomberglaw.com/ip-law/pfizer-scripps-sue-to-block-copy-of-most-expensive-heart-drug

Plus Lead Candidate Shows Preliminary Safety, Efficacy In Type Of Brain Cancer

 Plus Therapeutics Inc (NASDAQ: PSTV) reported data from the ReSPECT-LM study evaluating the company’s lead radiotherapeutic, rhenium (186Re) obisbemeda, for leptomeningeal metastases (LM).

LM is cancer in cerebrospinal fluid and leptomeninges, the membranes surrounding your brain and spinal cord.

The data were shared at the Society for Neuro-Oncology/American Society of Clinical Oncology Central Nervous System Cancer Conference.

Ten treated patients received a single escalating dose of rhenium (186Re) obisbemeda, which circulated throughout the cerebrospinal fluid (CSF) space within minutes following administration and had durable CSF retention for at least seven days.

No dose-limiting toxicities were observed, and a maximum tolerated or feasible dose was not reached.

Most adverse events were mild (Grade 1, 58.7%) or moderate (Grade 2, 24%), with the majority not related to treatment.

Five of the ten treated patients remain alive with a median overall survival (OS) of 10 months.

CSF tumor cell counts decreased from pre-dose levels 28 days after treatment by up to 91% (mean decrease = 53%).

Increases in administered dose correlated with linear increases in absorbed dose to the target tissue were observed.

Non-CNS organ dosimetry analysis of rhenium (186Re) obisbemeda confirmed these radiation levels were low, with the spleen, liver, and bladder having the most prominent rhenium (186Re) obisbemeda clearance but still significantly below critical organ toxicity levels.

The FDA has approved continued dose escalation.

https://finance.yahoo.com/news/exclusive-plus-therapeutics-lead-candidate-120011013.html