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Researchers at Children’s Hospital of Philadelphia (CHOP) successfully developed and validated a new outcome measure to monitor disease severity and progression in patients with impaired skeletal muscle function caused by mitochondrial disease. This measure, named ‘Mitochondrial Myopathy-Composite Assessment Tool’ (‘MM-COAST’), is important to identify specific skeletal muscle and neurological problems in both children and adults with mitochondrial disease and may be used to measure response to treatment interventions in future clinical trials. The findings were published online in JCSM Clinical Reports.
Primary mitochondrial disease is a group of several hundred gene disorders that can result in a wide variety of debilitating symptoms. In particular, the disease can affect high-energy organs such as skeletal muscle and the brain. Mitochondrial myopathy refers to a subset within mitochondrial disease that predominantly impacts skeletal muscle function with symptoms of weakness, fatigue, and exercise intolerance.
Currently, no FDA-approved therapies exist for mitochondrial myopathy. One major barrier to developing effective therapies is the lack of specific outcome measures for mitochondrial disease. While validated and objective outcome measures exist in other neuromuscular disorders such as Spinal Muscular Atrophy (SMA) and Duchenne muscular atrophy, these focus mainly on muscle strength without capturing other key domains of mitochondrial myopathy such as exercise intolerance and muscle fatigue.
“Our findings demonstrate that identifying clinically meaningful, tolerable, and quantifiable outcome measures for mitochondrial myopathy in pediatric and adult patients is feasible,” said senior study author Zarazuela Zolkipli-Cunningham, MBChB, MRCP, an attending physician in the Mitochondrial Medicine Frontier Program at CHOP. “We identified specific clinical deficits in our patients that we would have otherwise not known about, as well as key differences in how myopathy symptoms manifest in pediatric and adult patients. The MM-COAST will enable us to accurately follow their symptoms over time in longitudinal studies and in future intervention trials.”
The MM-COAST outcome measurement evaluates a variety of key aspects of disease that contribute to the clinical problems in mitochondrial myopathy patients. Some of the measurements evaluate the degree of weakness in muscles of the elbows, hips and knees, wrists and ankles, muscle fatigue at the elbows and knees, balance, dexterity, and exercise capacity.
By integrating analyses across this series of measurements, the study team showed for the first time that mitochondrial myopathy patients presented with both proximal and distal muscle weakness, significantly impaired hand dexterity, and balance issues that differentially impacted adults and children.
“These findings are the result of the enormous multi-disciplinary effort it took to develop this first-ever validated mitochondrial myopathy outcome metric for both children and adults,” said study co-author Marni Falk, MD, an attending physician and Executive Director of the Mitochondrial Medicine Frontier Program. “Reaching this milestone of having a validated outcome measure specific for mitochondrial myopathy holds great promise that we will be able to directly improve the design and success of clinical intervention trials, as well as natural history studies, and, ultimately, the health and well-being of mitochondrial disease patients.”
This research was supported by a 2016 United Mitochondrial Disease Foundation Clinical Grant Award and the Children’s Hospital of Philadelphia Mitochondrial Medicine Frontier Program.
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Materials provided by Children’s Hospital of Philadelphia. Note: Content may be edited for style and length.

Would you like to live longer? It turns out that where you live, not just how you live, can make a big difference.
That’s the finding of an innovative study co-authored by an MIT economist, which examines senior citizens across the U.S. and concludes that some locations enhance longevity more than others, potentially for multiple reasons.
The results show that when a 65-year-old moves from a metro area in the 10th percentile, in terms of how much those areas enhance longevity, to a metro area the 90th percentile, it increases that person’s life expectancy by 1.1 years. That is a notable boost, given that mean life expectancy for 65-year-olds in the U.S. is 83.3 years.
“There’s a substantively important causal effect of where you live as an elderly adult on mortality and life expectancy across the United States,” says Amy Finkelstein, a professor in MIT’s Department of Economics and co-author of a newly published paper detailing the findings.
Researchers have long observed significant regional variation in life expectancy in the U.S., and often attributed it to “health capital” — tendencies toward obesity, smoking, and related behavioral factors in the regional populations. But by analyzing the impact of moving, the current study can isolate and quantify the effect that the location itself has on residents.
As such, the research delivers important new information about large-scale drivers of U.S. health outcomes — and raises the question of what it is about different places that affects the elderly’s life expectancy. One clear possibility is the nature of available medical care. Other possible drivers of longevity include climate, pollution, crime, traffic safety, and more.

A study led by researchers from Brigham and Women’s Hospital has established a new resource for exploring and understanding Alzheimer’s disease (AD) on an individualized level. The team generated induced pluripotent stem cell (iPSC) lines from over 50 different individuals for whom longitudinal clinical data, quantitative neuropathology data, and rich genetic and molecular profiling of brain tissue was also available. The team demonstrated the power of this new resource through a series of studies that turned these human stem cells into brain cells and then analyzed molecular pathways active in these living neurons in a dish. The team identified specific forms of amyloid beta-protein (Aβ) and tau protein associated with cognitive decline and AD, and uncovered signaling pathways influencing the production of these toxic species. Their findings are published in Neuron.
“We are finding that different genetic backgrounds in humans generate different profiles of Aβ and tau” said Tracy Young-Pearse, PhD, of the Brigham’s Division of Neurology. “Those stem cell derived neuronal profiles have a predictive nature, in terms of the clinical outcome of an individual’s Alzheimer’s disease. This large set of human cell lines from AD and cognitively normal people provide the scientific community with a powerful experimental system for untangling why some people develop AD and others do not.”
The study leveraged a large cross-institutional collaborative effort that follows a cohort of people from the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP) at Rush University. All individuals entered the ROS and MAP studies with no history of AD or any other neurological diagnosis, but over one third of them went on to develop AD over time. Stem cell lines were generated from blood samples of over 50 of these individuals, who lived to an average of 90 years of age. While the subjects were alive, detailed clinical records and full genome sequencing were collected for each person. After death, the brains of the deceased also were studied and compared to their cultured brain cells in a dish.
The researchers measured Aβ and tau generated by the stem cell-derived neurons and found that specific Aβ and tau species were associated with the levels of plaque and tangle deposition in the brain and the trajectory of cognitive decline.
“If you look across cell culture samples from 50 people, you can predict from the Aβ and tau profiles some features of the cognitive status of that person: their rate of cognitive decline and whether they developed AD, which is absolutely remarkable,” Young-Pearse said.
The authors recognize that, since participants of the ROS and MAP cohorts were primarily Caucasians of European origin, their observations may not be applicable to more diverse populations. The research team has already undertaken the development of 50 new iPSC lines which will be derived from people of color and non-Caucasian groups.
“This is a resource for the whole community, for scientists around the world to use,” said Young-Pearse. “We already have around 50 labs, all around the world, starting to use these cells in their studies.”
The research team is also exploring if the stem cell-derived neurons can be used to predict whether drugs like aducanumab, a new Alzheimer’s drug recently approved by the Food and Drug Administration, will be more effective in specific groups of AD patients.
“The new Alzheimer’s drug is an antibody that recognizes Aβ and clears it from the brain. Our work shows that different genetic backgrounds of human neurons produce different profiles of Aβ,” said Young-Pearse. “What our system provides is a platform to test who might be responsive to different AD therapeutics, for example, anti-Aβ and anti-tau immunotherapeutics. This will be important because neurons from different individuals produce different profiles of Aβ and tau, and different antibody cocktails may be more effective against one profile over another.”
The research team hopes to convey to the public that Alzheimer’s is usually not caused by a single genetic mutation but instead can have different sets of genes contributing to risk across different people. This means that the primary causes of AD can be varied, and therefore treatments may also need to be tailored to the underlying causes of disease.
“There’s a perception that this disease is one uniform disease that shows up and progresses the same way for everyone,” Young-Pearse said. “It’s important to understand that Alzheimer’s is actually quite heterogeneous in its underlying causes, ages of onset and disease course. This is the first time we have a system in place to study living human brain cells from many people to understand better why some develop AD in a very specific way and others are resistant to the disease.”
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When people set their own exercise goals — and then pursue them immediately — it’s more likely to result in lasting positive changes, according to a new study at the Perelman School of Medicine at the University of Pennsylvania. The results of this research are especially important because they were found among an underserved population that is at particularly high risk of having or developing heart conditions. The study was published in JAMA Cardiology.
“Most behavior change programs involve goal-setting, but the best way to design that process is unknown,” said lead author Mitesh Patel, MD, MBA, an associate professor of Medicine at Penn and vice president for Clinical Transformation at Ascension. “Our clinical trial demonstrated that physical activity increased the most when patients chose their goals rather than being assigned them, and when the goals started immediately rather than starting lower and gradually increasing over time. These findings are particularly important because the patients were from lower-income neighborhoods and may face a number of challenges in achieving health goals.”
This study consisted of 500 patients from low-income neighborhoods, mainly in West Philadelphia but also elsewhere in and outside of the city. Participants either had a cardiovascular disease or were assessed to have a near-10 percent risk of developing one within a decade. These high-risk patients stood to greatly gain from increased physical activity.
Patel’s previous work at the Penn Medicine Nudge Unit often focused on the use of gamification, a concept used to create behavioral change by turning it into a game. The work usually tested whether playing a game attached to physical activity goals could make significant increases against not playing a game, or between different versions of a game.
As with past studies, every participant was given a wearable step tracker that recorded their daily step counts through Penn’s Way to Health platform. But what set this study apart from many of its predecessors was that the main outcomes of the research were less about participation in the games themselves and more about how goals were established, as well as when participants were encouraged to pursue them.
Once every participant got their wearable step counter, they were given a week or two to get used to it. This time period also functioned as a baseline-setting period for everyone’s pre-intervention daily step count. After that, participants were randomly assigned to the control group, which didn’t have step goals or games attached, or one of the gaming groups with goals.

A new study from scientists at Emory Vaccine Center and Winship Cancer Institute of Emory University reports that the immune cells that are the major targets of immune checkpoint inhibitors are present in tumors from head and neck cancer patients.
The study focuses on head and neck tumors that are positive for human papillomavirus (HPV), which is becoming one of most common types of head and neck cancers treated in the Western world. The results are scheduled for publication in Nature.
It suggests checkpoint inhibitors, which have transformed the treatment of several types of cancer, could be uniquely effective against this type of head and neck cancer. The results also indicate that the experimental approach of therapeutic vaccination for HPV+ cancer could be broadened to include more elements of the virus, to potentially trigger a broader and stronger immune response.
Researchers from Rafi Ahmed’s lab at Emory Vaccine Center collaborated with the co-directors of the Winship Head and Neck Cancers working group, oncologists Nabil Saba, MD and Mihir Patel, MD, to obtain samples from patients with head and neck tumors early in the course of treatment.
“About five years ago, we began to have an influx of patients that sought out our center for surgical treatment,” Patel says. “We often heard some variation of a similar story: I was sick with cold-like symptoms and once that resolved this I noticed swelling in a lymph node on the side of my neck. Stories like this made us think about how the immune system might play a unique role, different than typical smoking-related head and neck cancers.”
The team wanted to learn more about the different kinds of CD8 or “killer” T cells present within the cancers; CD8 T cells are specialized immune cells capable of detecting and killing virus-infected or tumor cells, if they are not constrained by regulatory signals. The inhibitory receptor PD-1 is highly expressed on exhausted CD8 T cells in chronic viral infections and cancer, and stem-like PD-1+ CD8 T cells are crucial for maintaining tumor-specific CD8 T cell responses. The majority of currently available checkpoint inhibitors, such as pembrolizumab and nivolumab, block the PD-1 signaling pathway.

Human evolution has provided us a level of protection from the existential threat of cold temperature with the capacity to produce heat from fat stored in the body. However, with age, people become more susceptible to cold as well as inflammation and metabolic problems which can lead to a host of chronic diseases. Researchers at Yale and the University of California-San Francisco (UCSF) have found one culprit in this process — the same immune cells within fat that are designed to protect us from cold temperatures.
In a new study, they find that the fat tissue of older mice loses the immune cell group 2 innate lymphoid cells (ILC2) which restore body heat in presence of cold temperatures. But in a cautionary tale for those seeking easy treatments for diseases of aging, they also found that stimulating production of new ILC2 cells in aging mice actually makes them more prone to cold-induced death.
“What is good for you when you are young, can become detrimental to you as you age,” said Vishwa Deep Dixit, the Waldemar Von Zedtwitz Professor of Comparative Medicine and of Immunobiology and co-corresponding author of the study.
The results are published Sept. 1 in the journal Cell Metabolism.
Dixit and his former colleague Emily Goldberg, now an assistant professor at UCSF, were curious about why fat tissue harbors immune system cells, which are usually concentrated in areas often exposed to pathogens like nasal passages, lungs, and skin. When they sequenced genes from cells of old and young mice they found that older animals lacked ILC2 cells, a deficit which limited their ability to burn fat and raise their body temperature in cold conditions.
When scientists introduced a molecule that boosts the production of ILC2 in aging mice, the immune system cells were restored but the mice were surprisingly even less tolerant of cold temperatures.
“The simple assumption is that if we restore something that is lost, then we are also going to restore life back to normal,” Dixit said. “But that is not what happened. Instead of expanding healthy cells of youth, the growth factor ended up multiplying the bad ILC2 cells that remained in fat of old mice.”
But when researchers took ILC2 cells from younger mice and transplanted them into older mice, they found, the older animals’ ability to tolerate cold was restored.
“Immune cells play a role beyond just pathogen defense and help maintain normal metabolic functions of life,” Dixit said. “With age, the immune system has already changed and we need to be careful how we manipulate it to restore the health of elderly.”
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Materials provided by Yale University. Original written by Bill Hathaway. Note: Content may be edited for style and length.

In March 2020, not long after the first cases of COVID-19 were reported locally, health officials in the city of St. Louis and St. Louis County issued emergency public health orders intended to reduce interactions between people and slow the transmission of the novel respiratory virus. Such action likely saved thousands of lives in the region, according to new research led by Washington University School of Medicine in St. Louis.
An analysis indicates that a delay of even two weeks in issuing local public health orders could have increased the number of deaths almost sevenfold in the city and county.
The researchers analyzed an epidemiological model to examine what was likely to have happened if the epidemic trajectory in St. Louis early in March had continued without the enactment of behavior-focused public health policies for another one, two and four weeks.
The research, published Sept. 1 in JAMA Network Open, demonstrates the importance of early and coordinated implementation of local public health policies in reducing deaths from the pandemic, particularly during a critical window at the onset of a new epidemic.
“We heard a lot about the dire situations in cities such as New York and Boston in the early part of the pandemic, where thousands of people died and hospitals were completely overwhelmed, but whether a similar situation would have happened in St. Louis is not obvious,” said lead author Elvin H. Geng, MD, a professor of medicine. “Some may argue that because the same thing didn’t happen here, it could never have happened here and that, therefore, early social-distancing policies were an overreaction. But our data suggest that a large number of deaths due to the pandemic was indeed possible in St. Louis, and therefore, the early implementation of public health orders helped prevent the number of deaths that cities such as New York and other places experienced.”
The first known case of COVID-19 in St. Louis County was reported March 7, 2020. By March 13, the city and county had banned large gatherings. Four days later, they closed bars and restaurants, and the next day, March 18, they ordered all public schools to close their doors. On March 23, the city and county issued shelter-in-place orders. With these public health measures, area hospitals experienced a total of 2,246 COVID-19 hospitalizations and 482 deaths attributed to COVID-19 by June 15, 2020.

Blood and urine tests could lead to faster and less invasive methods to diagnose and monitor various types of tumors, new research indicates. Two studies led by Washington University School of Medicine in St. Louis describe the potential of liquid biopsies to identify and track tumor growth in two very different cancers: bladder cancer and peripheral nerve tumors. Despite the differences between these cancers and their associated biopsies, the studies demonstrate the possible benefits of this relatively new tool in the fight against cancer.
Both studies appear in the Aug. 31 issue of PLOS Medicine, which is a special issue of the journal dedicated to liquid biopsies.
One study reports the development of a urine biopsy to monitor bladder cancer. With an easy to collect urine sample, doctors could determine whether the initial treatment eradicated the cancer or left some remnants of disease behind. That knowledge could lead to fewer patients undergoing unnecessary surgeries. The second study describes a blood biopsy to diagnose a tumor of the sheath — or lining — that covers peripheral nerves. This rare cancer is caused by an inherited genetic disorder called neurofibromatosis type 1 (NF1). In patients with NF1, it is difficult to determine whether tumors developing in the nerve sheath are benign or malignant.
“Our studies demonstrate ways that cancer management could improve with liquid biopsies that accurately diagnose and monitor tumors at various stages of the disease,” said Aadel A. Chaudhuri, MD, PhD, an assistant professor of radiation oncology and the senior author of both papers. Chaudhuri also treats patients at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.
“For bladder cancer, if a urine biopsy can detect whether the early chemotherapy totally eradicated the tumor, it could help some patients avoid major surgery to remove the bladder,” he said. “And for NF1, if we can distinguish between tumors that are cancerous versus precancerous, we open the door to early cancer detection in hereditary conditions that predispose people to developing cancer.”
Patients with bladder cancer that has invaded the underlying muscle typically undergo chemotherapy to shrink the tumor, followed by surgery to remove the bladder. Bladder removal, which also can include removal of the prostate and seminal vesicles for men, and removal of the uterus, ovaries and part of the vagina for women, reduces the risk of the cancer returning. But some patients may respond well to the initial chemotherapy and not need to have the bladder or nearby organs removed. Unfortunately, there is no way today to identify which patients may not need to undergo bladder removal, a procedure that has a major impact on quality of life. The urine biopsy that Chaudhuri and his colleagues have implemented could, in the future, be a way to determine which patients may safely avoid bladder removal.

A new USC study published in the journal Pediatrics finds a heightened risk of death from medical causes for infants with histories of reported maltreatment, suggesting a need for ongoing care coordination between the child protection system and pediatric health providers.
“Newborns in families involved with the child protection system reflect a highly vulnerable group and it is not surprising that their rates of death are elevated relative to infants never reported,” said study author Janet Schneiderman, a research associate professor emerita and former chair of the Department of Nursing at the USC Suzanne Dworak-Peck School of Social Work.
“Families with children who are reported to the child protection system often have risk factors that make providing adequate care for their children or meeting their children’s health care needs more difficult, especially during infancy.”
Researchers used a dataset for analysis comprised of birth and death records for all children born in California between 2010 and 2016 obtained from the California Department of Public Health, and administrative child protection system and foster care placement records made available through a data-sharing agreement between USC, the California Department of Social Services and the Children’s Data Network.
After adjusting for baseline risk factors, the researchers found that the risk of death from medical causes among infants reported for maltreatment was two to three times greater than observed for infants never reported. Among infants reported for maltreatment, the study found that periods of foster care placement reduced the risk of infant death due to medical causes by roughly half.
“Foster care placement was found to be protective against infant death from medical causes, highlighting the preventable nature of many of these deaths and raising questions of missed opportunities to ensure health and other preventive services for infants who remain at home,” Schneiderman said.
“Only one quarter of infants reported for maltreatment spent any time in foster care, and infant death is a rare event. The emergence of statistically significant differences in risk of preventable death is provocative and suggests that more intensive case management and health care supports are needed for infants remaining at home following allegations of abuse or neglect,” said co-author Emily Putnam-Hornstein, a distinguished scholar at USC, the John A. Tate Distinguished Professor for Children in Need at the University of North Carolina School of Social Work and co-director of the Children’s Data Network.
In addition to Schneiderman and Putnam-Hornstein, the study was authored by John Prindle, research assistant professor for the Children’s Data Network at the USC Suzanne Dworak-Peck School of Social Work.
The study was supported by The Conrad N. Hilton Foundation and the Heising-Simons Foundation, and data infrastructure support from First 5 LA for the Children’s Data Network.
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Materials provided by University of Southern California. Note: Content may be edited for style and length.

Research continues to mount indicating that many people who’ve had COVID-19 go on to suffer a range of adverse conditions months after their initial infections. A deep dive into federal health data adds to those concerns, pointing to a significant decline in kidney function among those dubbed COVID-19 long-haulers — and even among those who had mild infections of the virus.
The data, plumbed by researchers at Washington University School of Medicine in St. Louis and the Veterans Affairs St. Louis Health Care System, show that those infected with SARS-CoV-2 are at an increased likelihood of developing kidney damage as well as chronic and end-stage kidney diseases.
The study is published online Sept. 1 in the Journal of the American Society of Nephrology.
Known as the silent killer, kidney dysfunction and disease tend to be free of pain and other symptoms — so much so that the National Kidney Foundation estimates that 90% of people with ailing kidneys don’t know it. Kidney disease affects 37 million people in the U.S. and is one of the nation’s leading causes of death.
“Our findings emphasize the critical importance of paying attention to kidney function and disease in caring for patients who have had COVID-19,” said senior author Ziyad Al-Aly, MD, an assistant professor of medicine at Washington University. “If kidney care isn’t an integral part of COVID-19 post-acute care strategy, then we will miss opportunities to help potentially hundreds of thousands of people who have no idea that their kidney function has declined due to this virus. This is in addition to the millions of Americans who suffer from kidney disease not caused by COVID-19.”
The findings coincide with a surge in COVID-19 infections spurred by the delta variant. More than 38 million people have been diagnosed with the virus since the pandemic started.