Publisher Health

Many human experiences were uniquely altered during the COVID-19 pandemic including a significant rise in the number of people seeking outdoor recreation options during quarantine. In a series of studies looking at this trend, researchers at the University of New Hampshire found a dramatic increase during the pandemic of visitors to the parks and protected areas of New England that resulted in significant social, situational and ecological impacts on people’s behavior, decision making and experience quality.
“At the height of the pandemic, in the summer of 2020, outdoor recreation visitation within New England national forests increased by more than 60%, or approximately two million visitors, a majority of which came from out of state,” said Michael Ferguson, assistant professor of recreation management and policy. “While it was great to see so many people rediscovering the outdoors and taking advantage of recreation opportunities, it also raised questions and concerns about these already overwhelmed natural resources.”
The extensive suite of research, which includes a study recently published in the journal Society and Natural Resources, assesses the status of the so-called outdoor renaissance at the peak of the pandemic by examining visitation increases and shifts in behavior and decision making at the White Mountain National Forest and the Green Mountain National Forest. While the pandemic fueled visitation issues, these national forests were already seeing significant problems as early as 2017, including social (crowding and conflict), situational (site access and litter) and ecological (snowpack and ticks). During the summer of 2020, resource managers at the White Mountain National Forest commissioned the researchers to take a closer look at these concerns. The results of this study, published in the Journal of Outdoor Recreation and Tourism, found never-before-seen visitation numbers resulting in even more pervasive recreation challenges including long traffic lines, lack of parking, trail congestion and unprecedented instances of overcrowding and discord.
However, researchers found for the most part, visitors were largely able to cope and deal with most of the situations they encountered, but the one factor that was consistently difficult for them to tolerate was visitor conflict. This included arguments or disagreements, mostly between in-state and out-of-state visitors, largely based on perceived violations of pandemic safety protocols like not wearing masks or honoring physical distancing.
“Our data and modeling suggest that approximately 10% of annual visitation, which represents nearly 400,000 visitors, noted they would likely never return for outdoor recreation because of the issues they experienced,” said Ferguson.
To validate these initial findings, the researchers took a deeper dive into the impact of the pandemic on outdoor recreation visitors, with a specific focus on historically marginalized populations. This paper, published in the Journal of Outdoor Recreation and Tourism, confirmed the huge surge in national forest visitation during the pandemic and explored the significant increase in adverse interactions. The researchers also found that historically marginalized populations stated unique hurdles. For instance, low income visitors reported significantly less substitution options as opposed to high income visitors and female visitors reported significantly higher instances of conflict during the pandemic.
“COVID-19 unleashed a phenomenon that we didn’t anticipate,” said Ferguson. “It really changed the outdoor recreation experience and the manner in which these resources and experiences must be managed.”
Researchers say more studies are needed to determine next steps but hope this extensive research will help pinpoint continued issues and improve the decision-making process for resource managers, elected officials and visitors. The study team also noted that many parks and protected areas across the country experienced similar issues and moved to managed access systems to combat increasing visitation. Researchers are hopeful that future studies will help determine the best solutions for the New England national forest system.
Funding for this research was provided by the USDA Forest Service.
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Materials provided by University of New Hampshire. Original written by Robbin Ray. Note: Content may be edited for style and length.

A new study led by UC San Francisco has shown that people who are vaccinated against SARS-CoV-2, and have a history of certain psychiatric conditions, have a heightened risk of COVID-19 — a finding that may be related to impaired immune response as well as risky behaviors associated with some disorders.
The researchers from UCSF and the San Francisco VA Health Care System found that patients over 65 with substance abuse, psychotic disorders, bipolar disorder, adjustment disorder and anxiety, faced increased risks of up to 24% for breakthrough COVID. For those under 65, risks were up to 11% higher than for those without a psychiatric history.
For both age groups, data was adjusted for age, sex, race, ethnicity and vaccine type, as well as for smoking and underlying conditions like obesity, diabetes, sleep apnea, cardiovascular, lung, kidney and liver diseases, HIV and cancer.
In the study, which publishes on April 14, 2022, in JAMA Network Open, researchers tracked data from more than a quarter of a million U.S. Department of Veterans Affairs patients, who had completed their vaccine regimen and had at least one test for SARS-CoV-2. Just over a half (51.4%) of the patients had received at least one psychiatric diagnosis within the last five years and 14.8% developed breakthrough COVID, confirmed by a positive test.
Waning Immunity, Less Protection to New Variants May Explain Higher Rates
“Our research suggests that increased breakthrough infections in people with psychiatric disorders cannot be entirely explained by socio-demographic factors or pre-existing conditions,” said senior author Aoife O’Donovan, PhD, of the UCSF Weill Institute for Neurosciences and the San Francisco VA Health Care System. “It’s possible that immunity following vaccination wanes more quickly or more strongly for people with psychiatric disorders and/or they could have less protection to newer variants.”
A study earlier this year, led by the same UCSF researchers, found that people with elevated anxiety and probable post-traumatic stress disorder, conditions associated with impulsivity, were more likely to engage in behaviors that put them at higher risk for COVID.

More than 2,000 children die every day around the world simply because they lack clean drinking water, according to the U.S. Centers for Disease Control.
Engineers, including those at Tufts, have devised simple, low-cost ways to purify drinking water in low-income countries using chlorine, but a common concern is that adding chlorine to water could harm the beneficial bacteria in children’s developing gut microbiomes, which play an important role in keeping health intact.
Now a team of scientists led by Tufts, the University of California at Berkeley, the International Centre for Diarrheal Disease Research, Bangladesh, and Eawag in Switzerland have found that using chlorine to treat drinking water in Dhaka, Bangladesh does not disrupt the normal population of bacteria in the digestive tract of children, in addition to reducing diarrhea and antibiotic use.
The children’s microbiomes — tested from stool samples collected one year after the dispensers were installed — had a similar diversity and abundance of bacteria as children who didn’t receive chlorinated water. Some slight differences were observed, including the enrichment of beneficial bugs and increases in the presence of some antibiotic resistance genes, but those changes were small and the overall make-up of their microbiomes was similar.
While chlorine inactivates microorganisms present in water during storage, transport, and delivery through the tap, this study suggests that it’s not killing the good bacteria after the chlorinated water is consumed. In fact, by keeping the bad bugs out of the water supply, chlorination is allowing kids’ microbiomes to thrive and do their good work maintaining health.
That’s very important especially in the first few years of life. The gut microbiome of infants is seeded at birth, then grows and stabilizes to its adult-like state by the time a child is about three years old. The progressive colonization by different bacteria in the microbiome may be important to several developmental milestones related to metabolism and weight maintenance, allergy development, disease susceptibility, and even mental health.
“No doubt further studies may be helpful for understanding all the long-term health effects of drinking chlorinated water,” said Maya Nadimpalli, research assistant professor in civil and environmental engineering at Tufts, “but this study makes it clear that the microbiome is protected after at least one year of exposure, so that the benefits of water chlorination — which can save hundreds of thousands of lives each year — continue to outweigh diminishing concerns about its safety.”
Amy Pickering, formerly of Tufts and now Blum Center Distinguished Chair in Global Poverty and Practice at the University of California, Berkeley, has been working on developing and field testing automated chlorination devices that are compatible with water infrastructure in Africa and Asia.
“It’s very encouraging that such a widely used and low-cost water treatment method doesn’t harm children’s developing microbiomes,” said Pickering, who led the original trial and this study’s research team.
Nadimpalli, whose research is conducted in collaboration with the Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance at Tufts, notes that since children in Bangladesh are frequently exposed to pathogens, they are also treated with antibiotics at a rate five times higher than children in the U.S.
“The treatments themselves have a harmful effect on diversity in the gut microbiome, and you end up with worse health outcomes and potentially more antibiotic-resistant pathogens,” she said. “So chlorination can help reduce incidence of disease, limit use of antibiotics, and still keep microbiomes healthy.”
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Materials provided by Tufts University. Original written by Mike Silver. Note: Content may be edited for style and length.

Ovarian cancer is a difficult to diagnose malignancy that is often caught at a more advanced stage. Treatments for this cancer have changed little over the past few decades, with surgery and chemotherapy being the most common therapeutic approaches. Immunotherapy, a type of treatment that activates a patient’s immune system to target cancer cells, has been successful in many diseases but not ovarian cancer and it is unclear why.
Researchers at Moffitt Cancer Center want to improve their understanding of the immune environment in ovarian cancer in hopes of making immunotherapy an option for these patients. In a new study published in Cancer Cell, they report on key characteristics of immune cells in ovarian cancer and identify cell types important for mediating an immune response.
Checkpoint inhibitors are a specific type of immunotherapy that work by activating an immune cell called T cells. In order for checkpoint inhibitors to work, patients must have T cells that are ready to be activated in close proximity to tumor cells. Ovarian cancer is considered a type of tumor that should be impacted by checkpoint inhibitors because of T cell presence; yet clinical studies in ovarian cancer for these drugs have not been successful.
Moffitt researchers, led by Immunology Department Chair Jose Conejo-Garcia, M.D., Ph.D., wanted to determine whether ovarian cancer has the proper T cells to initiate an immune response and characterize the properties of the T cells present within ovarian cancer tumors. They performed a comprehensive analysis of ovarian cancer patient samples at the single-cell and tissue levels. They discovered that ovarian cancer is an immunogenic type of tumor that should be impacted by drugs that activate the immune system; however, immune activity against tumor cells is dependent on a small subset of immune cells.
The researcher team analyzed the types of T cells present in ovarian tumors and discovered that tissue-resident memory like T cells do a better job of recognizing tumor cells than T cells that are circulating and infiltrating the tumor. They also discovered that tissue-resident memory like T cells arise from circulating T cells and undergo a differentiation process into a tissue-resident memory stem cell that can generate T cells that actively target cancer cells. Some of these active T cells will eventually differentiate into an exhausted, inactivated state. The researchers confirmed that tissue-resident memory stem cells were important for anti-tumor immune activity by demonstrating that high numbers of them were associated with improved patient survival in ovarian cancer.
Interestingly, some of these lymphocytes show features of trogocytosis, a process where T cells take up a chunk of the membrane of target tumor cells. A trajectory of differentiation of tissue-resident memory T cells from stemness to irreversible exhaustion, in addition to evidence of trogocytic activity, identifies the T cells truly relevant to determine ovarian cancer patients’ outcome.
These results demonstrate that ovarian cancer, despite resistance to existing immunotherapies, is indeed an immunogenic disease and provide a roadmap for the design of improved immunotherapy options, which could be applicable to other tumors with similar mutational burden.
This study was supported by the National Institutes of Health (R01CA157664, R01CA124515, R01CA178687, R01CA211913, U01CA232758, R01CA184185, RO1CA262121, T32CA009140, P30CA076292) and the American Cancer Society.
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Materials provided by H. Lee Moffitt Cancer Center & Research Institute. Note: Content may be edited for style and length.

A study at McMaster University has found that brown adipose tissue (BAT) is less active in boys with obesity compared to boys with a normal body mass index (BMI).
Senior author Katherine Morrison said that BAT, also known as brown fat, helps the body burn regular fat and is activated by cold, but her research team noticed reduced BAT activity in the boys with obesity in response to a cold stimulus.
The researchers of McMaster’s Centre for Metabolism, Obesity and Diabetes Research performed MRI scans to measure BAT activity in 26 boys between the ages of eight and 10. They studied the BAT tissue in the neck before and after one hour of exposure to a cold suit set at a temperature of 18 degrees Celsius. The patient sample included 13 boys with a normal BMI and the same number again with obesity, in the first study of its kind in children.
“The promise of this study is that if we can better understand BAT and how to mimic or stimulate its effects, it might offer us new therapies to treat obesity,” said Morrison, a professor in the university’s Department of Pediatrics and pediatrician at the McMaster Children’s Hospital.
“Beyond helping families improve their nutrition, physical activity, and sleep, we have few treatments to assist children and adolescents with obesity. There are new medications that reduce appetite used in some adolescents. Investigating BAT activity holds out the hope of developing a new class of drugs that increase the amount of energy you burn.”
However, Morrison said that it is still unknown whether a lack of BAT activity causes obesity, or if the condition simply impairs brown fat’s ability to burn energy.
She said that newborn babies have large amounts of BAT, but it steadily decreases through childhood, so that by adulthood it is mostly present only in the neck region. The reason for decreasing brown fat levels in children remains unknown.
Morrison said her team used MRI scans to measure BAT activity as it did not expose the boys to ionizing radiation, unlike CT or PET scans. This potential safety risk has impeded research in children until now.
This study was funded by an internal grant from the Boris Family and external funding for the study was provided by the Canadian Institutes of Health Research.
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Materials provided by McMaster University. Note: Content may be edited for style and length.

Nearly 12 years after the Deepwater Horizon oil spill, scientists are still examining the potential health effects on workers and volunteers who experienced oil-related exposures.
To help shape future prevention efforts, one West Virginia University researcher — Caroline Groth, assistant professor in the School of Public Health’s Department of Epidemiology and Biostatistics — has developed novel statistical methods for assessing airborne exposure. Working with collaborators from multiple institutions, Groth has made it possible for researchers to characterize oil spill exposures in greater detail than has ever been done before.
With very few Ph.D. biostatisticians in the area of occupational health, there were few appropriate statistical methodologies for the assessment of inhalation exposures for the GuLF STUDY, a study launched by the National Institute of Environmental Health Sciences shortly after the Deepwater Horizon oil spill. The purpose of the study, which is the largest ever following an oil spill: examine the health of persons involved in the response and clean-up efforts. Groth was part of the exposure assessment team tasked with characterizing worker exposures and led by Patricia Stewart and Mark Stenzel.
Groth’s statistical methods, which she began in 2012, laid the framework for a crucial step for determining whether there are associations between exposures and health outcomes from the oil spill and clean-up work, which involved over 9,000 vessels deployed in the Gulf of Mexico waters across Alabama, Florida, Louisiana and Mississippi and tens of thousands of workers on the water and on land.
The Deepwater Horizon oil spill is considered the largest marine oil spill in the history of the U.S.
“Workers were exposed differently based on their activities, time of exposure, etc., and our research team’s goal was to develop exposure estimates for each of those scenarios and then link them to the participants’ work history through an ‘exposure matrix,'” Groth said.

Some brain cancers are easier to treat than others. Many solid tumors can be carefully excised by a skilled neurosurgeon, but others, such as diffuse midline gliomas, or DMGs, are much trickier. Children who have been diagnosed with a DMG tumor are projected to live for less than a year.
New research from the University of Pittsburgh School of Medicine points to a potentially better, non-invasive way to treat these tumors in the future.
In a paper published in Nature Cancer today, physician-scientists from Pitt and UPMC Children’s Hospital of Pittsburgh discovered that DMG tumors are uniquely dependent on methionine — an amino acid that humans must receive from food. Developing drugs that specifically target methionine-processing machinery in cancerous cells in the brain but not in the rest of the body might pave way for new non-invasive treatments.
“The Achilles’s heel of these tumors is that they are rapidly growing and use a lot of nutrients,” said Sameer Agnihotri, Ph.D., assistant professor of neurological surgery at Pitt. “Combining metabolic approaches — changes in diet — with next-generation scientific tools might become a way of harnessing our understanding of how nutrient needs of cancer cells differ from normal cells and lead to more effective personalized cancer therapies in the future.”
Brain cancer is the second-most common type of cancer in children, surpassed only by leukemia. But unlike leukemia, which has relatively high survival rates thanks to the medical advancements of the last century, brain cancers represent the No. 1 cause of cancer deaths among children. And, of all brain cancers, DMGs are especially deadly.
Midbrain, where DMG tumors often arise, is a critical connection point linking the brain cortex — an area responsible for complex information processing, logical reasoning and thinking — to the spinal cord. Because those tumors are buried deep inside the brain, surgery is often impossible, and they often don’t respond to radiation therapy.

Researchers from Georgia Tech’s Colleges of Engineering and Computing have completed the first published study on the link between America’s mass transit use and Covid-19 cases at the beginning of the pandemic.
Using data from the Federal Highway Administration’s National Household Travel Survey, the team looked at the nation’s 52 largest metropolitan areas and each community’s likelihood of riding buses and trains. They then compared the numbers with the 838,000 confirmed Covid cases on the Johns Hopkins Center for Systems Science and Engineering’s dashboard from Jan. 22 — May 1, 2020.
The timeframe covers the initial days, weeks, and months of the pandemic, before mask mandates were in place and prior to widespread social distancing. Ventilation on public transit had yet to be addressed, along with other public health measures that have since become the norm.
The study found that cities with high-usage public transportation systems displayed higher per capita Covid incidence. This was true when other factors, such as education, poverty levels, and household crowding, were accounted for. The association continued to be statistically significant even when the model was run without data from transit-friendly New York City.
The paper, “Investigating the association between mass transit adoption and COVID-19 infections in US metropolitan areas,” is published in the journal Science of the Total Environment. While the researchers don’t suggest that transit is the sole cause of the high incidence rates, they say it could have been an important factor early in the pandemic.
“This is what we expected, but we wanted to run the models to know for sure. Policymakers shouldn’t make decisions based on what they assume to be true,” said Michael Thomas, one of the study’s co-authors and a Ph.D. student in Georgia Tech’s School of Computational Science and Engineering. “This study is similar to dusting off a dinosaur dig site and finding a leg bone. This isn’t the entire dinosaur. There are many ways of making the argument about Covid spread, and transit is just part of it.”
The team got the idea of tracking transit and Covid cases after watching early reports from Wuhan, China, and reflecting on how differences in public transportation systems may factor into pandemic spread patterns. As assumptions were being made about how American cities should react based on ridership patterns on the other side of the globe, Professor John Taylor thought the pandemic shouldn’t be treated as a “one size fits all” situation.

Researchers have published the results of a clinical trial that led the U.S. Food and Drug Administration to recently approve mitapivat for the treatment of adults with pyruvate kinase deficiency — a rare genetic condition that leads to the destruction of red blood cells, or hemolytic anemia. The primary results from the global, phase 3, randomized, placebo-controlled ACTIVATE trial, which was conducted by an international team including investigators at Massachusetts General Hospital (MGH), are published in the New England Journal of Medicine.
“The lifelong anemia associated with pyruvate kinase deficiency results in chronic fatigue, reduced exercise tolerance, and a reduced ability to concentrate at work or school, which can make it a challenge to get through even a normal day,” says lead author Hanny Al-Samkari, MD, a hematologist and clinical investigator at MGH and an assistant professor of Medicine at Harvard Medical School. “Moreover, most patients develop other potentially serious complications, like iron overload in the liver and/or heart (which can cause cancer or death), osteoporosis, gallbladder disease, blood clots, and other issues.”
Pyruvate kinase deficiency is characterized by mutations in the PKLR gene that encodes the pyruvate kinase enzyme in red blood cells. This enzyme is critical for maintaining red blood cells’ energy levels and, therefore, their normal life span. Mitapivat can activate and stabilize the mutated pyruvate kinase that’s expressed in patients’ red blood cells, thereby restoring the enzyme’s activity.
“This is a ‘disease modifying’ therapy because it targets the underlying problem to improve or eliminate anemia and potentially prevent or reverse many of the other complications associated with pyruvate kinase deficiency,” says Al-Samkari. “It is the first disease-modifying medication for pyruvate kinase deficiency, which up until now has been treated only with supportive measures like blood transfusion or removing a patient’s spleen.”
In the ACTIVATE trial designed and conducted by Al-Samkari and his colleagues, 80 patients were randomized to receive either mitapivat (5 mg twice daily, with potential escalation to 20 or 50 mg twice daily) or placebo for 24 weeks. The primary end point was a hemoglobin response (an indicator of red blood cell levels) that was sustained at two or more scheduled assessments at weeks 16, 20, and 24.
Sixteen of the 40 patients (40%) who received mitapivat had a hemoglobin response, compared with none of the patients who received placebo. Patients who received mitapivat also had a greater response than those who received placebo with respect to secondary end points, which included other markers of red blood cell health. Patients treated with mitapivat also had a significant improvement in quality of life compared with patients receiving placebo as measured by disease-specific instruments.
The most common adverse events were nausea (in 18% of patients in the mitapivat group and 23% of patients in the placebo group) and headache (in 15% of patients in the mitapivat group and 33% of patients in the placebo group).
“The opportunity to develop a disease-modifying therapy for a disease like pyruvate kinase deficiency not only helps patients with this disease but also brings hope to patients with other similar disorders,” says Al-Samkari. “Because energy is everything to red blood cells, this drug may help patients with more common anemias like sickle cell disease and thalassemia. We are looking at this right now in other clinical trials, and early studies have been very promising.”
Additional study authors include Frédéric Galactéros, MD, PhD, Andreas Glenthøj, MD, Jennifer A. Rothman, MD, Oliver Andres, MD, Rachael F. Grace, MD, Marta Morado-Arias, MD, D. Mark Layton, M.B., BS, Koichi Onodera, MD, Madeleine Verhovsek, MD, Wilma Barcellini, MD, Satheesh Chonat, MD, Malia P. Judge, BS, Erin Zagadailov, PharmD, Rengyi Xu, PhD,?Peter Hawkins, PhD, Vanessa Beynon, MD, Sarah Gheuens, MD, PhD, and Eduard J. van Beers, MD.
This work was supported by Agios Pharmaceuticals.

Combining a retrospective analysis of clinical records with in-depth laboratory studies, researchers at The University of Texas MD Anderson Cancer Center have discovered that vitamin E can enhance immunotherapy responses by stimulating the activity of dendritic cells in the tumor. The findings were published today in Cancer Discovery.
The researchers demonstrated that vitamin E directly binds and blocks the activity of the SHP1 checkpoint protein in dendritic cells, which increases antigen presentation and primes T cells for an anti-tumor immune response. The results point to possible new therapeutic approaches to improve immunotherapy outcomes, including combinations with vitamin E as well as directly targeting SHP1 in dendritic cells.
“This study broadens our understanding of factors that can influence responses to immunotherapies,” said corresponding author Dihua Yu, M.D., Ph.D., chair ad interim of Molecular & Cellular Oncology. “We demonstrated that vitamin E can reinvigorate dendritic cell antigen presentation via the inhibition of SHP1. These results indicate that vitamin E-treated or SHP1-silenced dendritic cells and dendritic cell-derived extracellular vesicles could be developed as potent immunotherapies for future clinical applications.”
Vitamin E connected with improved immunotherapy responses
Immune checkpoint inhibitors, a type of immunotherapy, provide long-lasting responses for many patients with cancer, but not all benefit. There is a need to understand these varied responses in order to improve outcomes for more patients.
Dietary supplements are thought to boost immunity, but little is known about the effects of supplements on immunotherapy activity. To explore the connection, the researchers performed a retrospective analysis of clinical data from MD Anderson patients treated with immunotherapy.