Publisher Health

Crowding in prisons dramatically increases the risk for COVID-19 infections among inmates, according to a new study by researchers at Massachusetts General Hospital (MGH). The authors of the study, published in JAMA Internal Medicine, argue that policy changes are necessary to protect the vulnerable population of incarcerated men and women.
Earlier studies found that the incidence of COVID-19 infection is significantly higher in prisons than in the general population, but the degree to which crowding contributed to the problem was unknown. The senior author of the JAMA Internal Medicine study, MGH infectious diseases physician Amir Mohareb, MD, has worked on a pro bono basis with several advocacy groups working to ensure that infection control measures are implemented in prisons during the coronavirus pandemic. One group he advised, Prisoners’ Legal Services of Massachusetts, was suing the state’s Department of Correction over its practices. Mohareb and his colleagues analyzed a trove of data in Massachusetts that allowed them to examine more closely what’s driving the high incidence of COVID-19 in prisons.
One element the data lacked was detailed information about each individual inmate who became ill, which would have allowed Mohareb and his team to study the characteristics of who got COVID-19 and who didn’t. However, they had other critical data, including weekly reports on the number of positive COVID-19 tests at 14 Massachusetts state prisons, the population of each prison, and the number of inmates the facility was designed to hold (known as design capacity). “So we asked, What are characteristics of these facilities that might lead to more COVID-19 transmission?” says Mohareb, who is also a researcher at MGH’s Medical Practice Evaluation Center.
Their analysis found that crowding at the facilities varied greatly during the observation period, with the population at some dropping as low as 25 percent of design capacity, while others were extremely crowded, reaching up to 155 percent of design capacity. Mohareb and his colleagues found that as facilities became more crowded, the threat to inmates rose: Every increase of 10 percentage points in a prison population relative to the facility’s design capacity raised the risk of getting infected with COVID-19 by 14 percent. As Mohareb notes, that means a facility doesn’t have to be exceeding its design capacity to increase the danger for inmates, since a prison that’s operating at 80 percent capacity is riskier than one at 70 percent capacity. “We may need to have stricter thresholds for where we draw the line on how crowded a facility can be,” he says.
To study the effect of crowding another way, Mohareb’s team calculated the percentage of inmates in each prison who were housed in single cells during each week of the observation period. They found that every 10-percentage-point increase in the proportion of inmates living in single cells reduced the risk of COVID-19 infection in that prison by 18 percent.
Similar to other studies, this investigation found that inmates in prisons have a significantly greater risk — more than sixfold — for becoming infected with COVID-19 compared to the general public. But in a novel finding, Mohareb and colleagues showed that infection rates in prisons tended to reflect those of their surrounding communities. “We found a very close association,” says Mohareb. When numbers of COVID-19 cases were low in Massachusetts during the summer of 2020, they tended to be low in prisons, too. And as numbers spiked in many communities late last year, they also soared in local prisons. “Prisons are intricately linked to their surrounding communities,” says Mohareb, noting that greater attention to infection control (through vaccination and routine testing) among guards, support staff, vendors, and others who come and go from these facilities is essential.
While COVID-19 vaccination became available to inmates in Massachusetts state prisons earlier this year, it is optional; what’s more, news reports indicate that a significant portion of prison workers remain unvaccinated. Mohareb and his coauthors argue that policymakers should strongly consider decarceration — releasing prisoners deemed to be at low risk for reoffending — as a way to lower the risk for COVID-19 in prisons. “It was the almost universal opinion of experts in public health, infectious disease and epidemiology from the start of the pandemic that prisons were going to be places of immense suffering unless inmates were released in a coordinated manner,” says Mohareb. “And that really didn’t happen.”
Mohareb is also an instructor in Medicine at Harvard Medical School (HMS). Abigail I. Leibowitz, the first author of the paper, completed this work while earning a master’s degree in public health at the Harvard T.H. Chan School of Public Health and is currently a medical student at the University of Colorado. Other authors include MGH infectious disease physician Mark Siedner, MD, MPH, an associate professor of Medicine at HMS, and MGH psychiatrist Alexander C. Tsai, MD, PhD, an associate professor of Psychiatry at HMS.
Support for this work was provided by the National Institutes of Health and the Sullivan Family Foundation.

An alarming percentage of children and adolescents are experiencing a global-wide mental crisis due to the COVID-19 pandemic according to a new University of Calgary study published in the medical journal JAMA Pediatrics.
The UCalgary study is a meta-analysis, pooling together data from 29 separate studies from around the world, including 80,879 youth globally. The new findings show that depression and anxiety symptoms have doubled in children and adolescents when compared to pre-pandemic times.
“Estimates show that one in four youth globally are experiencing clinically elevated depression symptoms while one in five have clinically elevated anxiety symptoms,” says Dr. Nicole Racine, PhD, a postdoctoral associate, clinical psychologist and lead author of the paper. Further alarming, these symptoms are compounding over time.
The UCalgary study — which incorporates 16 studies from East Asia, four from Europe, six from North America, two from Central and South America and one from the Middle East — also shows that older adolescents and girls are experiencing the highest levels of depression and anxiety.
“We know from other studies that rates of depression and anxiety in youth tend to ebb and flow with restrictions,” says Dr. Sheri Madigan, PhD, co-author of the paper, a UCalgary clinical psychologist and Canada Research Chair in Determinants of Child Development. “When more restrictions are imposed, rates go up. Being socially isolated, kept away from their friends, their school routines, and social interactions has proven to be really hard on kids.”
She adds: “When COVID-19 started, most people thought it would be difficult at the outset but that kids would be better over time, as they adjusted and got back to school. But when the pandemic persisted, youth missed a lot of milestones in their lives. It went on for well over a year and for young people that’s a really substantial period of their lives.”
For many adolescents that loss was especially impactful. “Once you enter adolescence you begin differentiating from your family members and your peers can actually become your most important source of social support,” says Racine. “That support was greatly reduced, and in some cases absent altogether, during the pandemic.”

Researchers have found a way to reduce organ rejection following a transplant by using a special polymer to coat blood vessels on the organ to be transplanted.
The polymer, developed by UBC medicine professor Dr. Jayachandran Kizhakkedathu and his team at the Centre for Blood Research and Life Sciences Institute, substantially diminished rejection of transplants in mice when tested by collaborators at SFU and Northwestern University.
“We’re hopeful that this breakthrough will one day improve quality of life for transplant patients and improve the lifespan of transplanted organs,” said Dr. Kizhakkedathu.
The findings were published today in Nature Biomedical Engineering.
The discovery has the potential to eliminate the need for drugs — typically with serious side effects — on which transplant recipients rely to prevent their immune systems from attacking a new organ as a foreign object.
Dr. Kizhakkedathu explained how that problem arises: “Blood vessels in our organs are protected with a coating of special types of sugars that suppress the immune system’s reaction, but in the process of procuring organs for transplantation, these sugars are damaged and no longer able to transmit their message.”
Dr. Kizhakkedathu’s team synthesized a polymer to mimic these sugars and developed a chemical process for applying it to the blood vessels. He worked with UBC chemistry professor Dr. Stephen Withers and the study’s co-lead authors, PhD candidate Daniel Luo and recent chemistry PhD Dr. Erika Siren.

Inspired by the sticky substance that barnacles use to cling to rocks, MIT engineers have designed a strong, biocompatible glue that can seal injured tissues and stop bleeding.
The new paste can adhere to surfaces even when they are covered with blood, and can form a tight seal within about 15 seconds of application. Such a glue could offer a much more effective way to treat traumatic injuries and to help control bleeding during surgery, the researchers say.
“We are solving an adhesion problem in a challenging environment, which is this wet, dynamic environment of human tissues. At the same time, we are trying to translate this fundamental knowledge into real products that can save lives,” says Xuanhe Zhao, a professor of mechanical engineering and civil and environmental engineering at MIT and one of the senior authors of the study.
Christoph Nabzdyk, a cardiac anesthesiologist and critical care physician at the Mayo Clinic in Rochester, Minnesota, is also a senior author of the paper, which appears today in Nature Biomedical Engineering. MIT Research Scientist Hyunwoo Yuk and postdoc Jingjing Wu are the lead authors of the study.
Natural inspiration
Finding ways to stop bleeding is a longstanding problem that has not been adequately solved, Zhao says. Sutures are commonly used to seal wounds, but putting stitches in place is a time-consuming process that usually isn’t possible for first responders to perform during an emergency situation. Among members of the military, blood loss is the leading cause of death following a traumatic injury, and among the general population, it is the second leading cause of death following a traumatic injury.

The risk that both tobacco and electronic cigarettes can pose to regular smokers’ health has been well documented, but a new UCLA study illustrates just how quickly vaping can affect the cells of even healthy younger nonsmokers.
The findings, published on Monday in JAMA Pediatrics, show that a single 30-minute vaping session can significantly increase cellular oxidative stress, which occurs when the body has an imbalance between free radicals — molecules that can cause damage to cells — and antioxidants, which fight free radicals.
“Over time, this imbalance can play a significant role in causing certain illnesses, including cardiovascular, pulmonary and neurological diseases, as well as cancer,” said the study’s senior author, Dr. Holly Middlekauff, a professor of cardiology and physiology at the David Geffen School of Medicine at UCLA.
E-cigarettes, devices that deliver nicotine with flavoring and other chemicals in a vapor rather than smoke, are seen by many as a safer alternative to regular cigarettes, but research by Middlekauff and others has demonstrated that vaping is associated with a number of adverse changes in the body that can presage future health problems.
For the current study, 32 male and female study participants, who ranged in age from 21 to 33, were divided into three groups: 11 nonsmokers, nine regular tobacco cigarette smokers and 12 regular e-cigarette smokers. Middlekauff and her colleagues collected immune cells from each individual before and after a half-hour vaping session to measure and compare changes in oxidative stress among the groups.
The researchers performed the same process during a control session in which participants spent 30 minutes “sham-vaping,” or puffing on an empty straw.

If heart attacks blared a warning signal, patients would have a better chance of avoiding them. That’s the idea behind a new imaging technique developed by a Spartan-led team of researchers.
“We shine light into an artery where we’ve delivered certain types of particles that can absorb that light,” said Bryan Smith, an associate professor in Michigan State University’s College of Engineering. “As a product of the release of that energy, they can literally shout back at us in ways that we can detect and use to create 3D images.”
To be clear, the sound signal isn’t audible to human ears, but it’s easily captured by an ultrasound’s transducer. Thanks to Smith and his colleagues, this technique can now be used to directly image atherosclerotic plaques, the medical term for fatty clumps that accumulate in arteries that can lead to strokes and heart attacks.
The researchers showcased the new technique in mice, the first step towards advancing the technology for use in humans. The team published its results in an article that’s now available online in the journal Advanced Functional Materials. The journal will also feature the work as an inside cover story in a September issue.
“The power of our new technique is in its selectivity,” said Smith, who is the director of the Translational NanoImmunoEngineering Lab located at MSU’s Institute for Quantitative Health Science and Engineering, or IQ.
“There are certainly other methods to image plaques, but what distinguishes this strategy is that it’s cellular,” Smith said. “We’re specifically looking at the cells — called macrophages and monocytes — that are most responsible for making a plaque vulnerable in the first place.”
Although it’s difficult to prove whether a particular plaque is responsible for a stroke or heart attack in a patient, the prevailing idea is that vulnerable plaques are the most dangerous, Smith said. These are inflammatory plaques that can rupture and consequently block blood vessels.

Researchers from the group of Hans Clevers (Hubrecht Institute) corrected mutations that cause cystic fibrosis in cultured human stem cells. In collaboration with the UMC Utrecht and Oncode Institute, they used a technique called prime editing to replace the ‘faulty’ piece of DNA with a healthy piece. The study, published in Life Science Alliance on August 9th, shows that prime editing is safer than the conventional CRISPR/Cas9 technique. “We have for the first time demonstrated that this technique really works and can be safely applied in human stem cells to correct cystic fibrosis.”
Cystic fibrosis (CF) is one of the most prevalent genetic diseases worldwide and has grave consequences for the patient. The mucus in the lungs, throat and intestines is sticky and thick, which causes blockages in organs. Although treatments are available to dilute the mucus and prevent inflammations, CF is not yet curable. However, a new study from the group of Hans Clevers (Hubrecht Institute) in collaboration with the UMC Utrecht and Oncode Institute offers new hope.
Correcting CF mutations
The researchers succeeded in correcting the mutations that cause CF in human intestinal organoids. These organoids, also called mini-organs, are tiny 3D structures that mimic the intestinal function of patients with CF. They were previously developed by the same research group from stem cells of patients with CF and stored in a biobank in Utrecht. For the study, published in Life Science Alliance, a technique named prime editing was used to replace the piece of mutated DNA that causes CF with a healthy piece of DNA in these organoids.
Safer than CRISPR/Cas9
Prime editing is a newer version of the better-known gene editing technique CRISPR/Cas9. CRISPR/Cas9 cuts the DNA before correcting it. Although this corrects the mutated piece of DNA, it also causes damage in other regions in the genome. “In our study, prime editing proves to be a safer technique than the conventional CRISPR/Cas9. It can build in a new piece of DNA without causing damage elsewhere in the DNA. That makes the technique promising for application in patients,” says Maarten Geurts, first author on the publication.
Swelling
The mutations that cause CF are localized in the CFTR channel, which is present in the cells of various organs including the lungs. Due to the mutations, the channel does not function properly, leaving the layer of mucus that covers the cells with too little water: the mucus becomes sticky. The addition of a substance called forskolin causes healthy organoids to swell, but this does not happen in organoids with mutations in the CFTR channel. “We applied prime editing to the mutations, after which the treated organoids demonstrated the same response as the healthy organoids: they became swollen. That provided us with proof that our technique worked and replaced the mutated DNA,” Geurts explains.
Curing genetic diseases
Now that the researchers showed that the mutations that cause CF can be safely corrected, applications in the clinic come one step closer. “New variants of CRISPR/Cas9, such as prime editing, can safely correct mutations without causing damage in other regions of the DNA. This will hopefully enable us to cure or even prevent genetic diseases in the future.” But before that, some challenges still lie ahead for the researchers. The technique for example still needs to be adapted for safe use in humans. “But this is a great step towards successfully applying prime editing in the clinic,” Geurts concludes.
Hans Clevers is group leader at the Hubrecht Institute for Developmental Biology and Stem Cell Research and at the Princess Máxima Center for Pediatric Oncology. He is also University Professor at the Utrecht University and Oncode Investigator.
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Researchers used to believe that individual primary touch-sensitive neatly responded to specific types of touch. Now a Northwestern University study finds that touch-sensitive neurons communicate touch in a much messier and jumbled manner.
In the study, the team developed a new technique to stimulate rats’ whiskers in three dimensions while simultaneously recording first-stage touch-sensitive neurons in the rats’ brains. The researchers discovered that, instead of responding to distinct types of touch, these neurons — which are the first to receive early touch signals — responded to many types of touch and to varying degrees.
The research was published online todayin the Proceedings of the National Academy of Sciences.
“Many people used to think that each neuron was very precisely tuned for some aspect of the touch stimulus,” said Northwestern’s Mitra Hartmann, one of the study’s senior authors. “We didn’t find that at all. Some neurons respond more than others to some features of the stimulus, so there is some degree of tuning. But these neurons respond to many combinations of different forces and torques applied to the whisker.”
“When we compared all the recorded neurons, we found that the stimuli they responded to overlapped with each other but not perfectly,” added Nicholas Bush, the paper’s first author. “It’s similar to a painter’s palette: We expected to find a handful of ‘primary colors,’ where a neuron could be one of a few different types. But we found the ‘palette’ had already been mixed. Each neuron was a little different from all the others, but together they covered an entire spectrum.”
Hartmann is a professor of biomedical and mechanical engineering at Northwestern’s McCormick School of Engineering, where she is a member of the Center for Robotics and Biosystems. A former Ph.D. candidate in Hartmann’s laboratory, Bush now is a postdoctoral fellow at the Seattle Children’s Research Institute. Sara Solla, a professor of physiology at Northwestern University Feinberg School of Medicineand of physics and astronomy in the Weinberg College of Arts and Sciences, is the other senior author of the study.

In a randomized control study of 10 healthy young men, researchers compared how consuming the single amino acid leucine or its two-molecule equivalent, dileucine, influenced muscle-building and breakdown. They found that dileucine boosts the metabolic processes that drive muscle growth 42% more than free leucine does.
They report their findings in the Journal of Applied Physiology.
Leucine, isoleucine and valine all are branched-chain amino acids, famous among body builders and health enthusiasts for their purported muscle-enhancing benefits. Like other amino acids, they are the building blocks of proteins. But leucine also acts as a signaling molecule that triggers muscle-building pathways in cells, said University of Illinois Urbana-Champaign kinesiology and community health professor Nicholas Burd, who led the new research with kinesiology graduate student Kevin Paulussen.
Digestion breaks the chemical bonds between the amino acids that make up proteins, resulting in a stew of shorter molecules, including free amino acids and dipeptides. Previous studies have suggested that the small intestine absorbs dipeptides like dileucine more rapidly than their single-molecule counterparts, Burd said.
“But few studies have examined whether dileucine in the diet makes it into the blood as a dipeptide or is first broken down into two leucine molecules,” he said. “And no studies have examined its effects on acute muscle-building and breakdown.” Burd’s laboratory is one of a small number of research facilities set up to study muscle protein metabolism in human participants.
For the new study, participants came to the lab after a 12-hour fast and were infused with stable isotopes, chemical probes that allow researchers to track the process of muscle protein synthesis and breakdown in their muscles. Then biopsies of muscle tissue were taken from the upper leg.

Emergency department physicians who saw patients with a pulmonary embolism — a blood clot in the lung — were about 15% likelier over the next 10 days to test subsequent patients for the same thing.
Rules of thumb, also known as heuristics, could influence how physicians deliver care. One such rule of thumb is the “availability heuristic,” under which a person assesses an event’s likelihood by how easily the event comes to mind. For physicians, recent conditions seen may be particularly notable. Under this heuristic, if a physician sees a condition in a recent patient, they may be more likely to test for the condition in the next patient they see.
Dr. Dan Ly, assistant professor of medicine in the division of general internal medicine and health services research at the David Geffen School of Medicine at UCLA, examined 2011 to 2018 data from 7,400 emergency department physicians who cared for 417,000 patients with shortness of breath at 104 Veterans Affairs hospitals. He examined how often a physician tested for pulmonary embolism immediately after seeing the same diagnosis in a previous patient.
The findings provide large-scale evidence that the availability heuristic plays a role in how physicians make complex testing decisions. For patients, how physicians make care decisions may be influenced by things such as what that physician saw in the patient they had just cared for. For physicians, awareness of such heuristics may help lessen their influence.
This work was supported by the National Institute on Aging.
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