Publisher Health

New evidence shows that patients with Long COVID syndrome continue to have higher measures of blood clotting, which may help explain their persistent symptoms, such as reduced physical fitness and fatigue.
The study, led by researchers from RCSI University of Medicine and Health Sciences, is published in the Journal of Thrombosis and Haemostasis.
Previous work by the same group studied the dangerous clotting observed in patients with severe acute COVID-19. However, far less is known about Long COVID syndrome, where symptoms can last weeks to months after the initial infection has resolved and is estimated to affect millions of people worldwide.
The researchers examined 50 patients with symptoms of Long COVID syndrome to better understand if abnormal blood clotting is involved.
They discovered that clotting markers were significantly elevated in the blood of patients with Long COVID syndrome compared with healthy controls. These clotting markers were higher in patients who required hospitalisation with their initial COVID-19 infection, but they also found that even those who were able to manage their illness at home still had persistently high clotting markers.
The researchers observed that higher clotting was directly related to other symptoms of Long COVID syndrome, such as reduced physical fitness and fatigue. Even though markers of inflammation had all returned to normal levels, this increased clotting potential was still present in Long COVID patients.
“Because clotting markers were elevated while inflammation markers had returned to normal, our results suggest that the clotting system may be involved in the root cause of Long COVID syndrome,” said Dr Helen Fogarty, the study’s lead author, ICAT Fellow and PhD student at the Irish Centre for Vascular Biology in the RCSI School of Pharmacy and Biomolecular Sciences.
This work was funded by the Welcome Trust, the Health Research Board (HRB) Irish Clinical Academic Training (ICAT) programme as well as the HRB-funded Irish COVID-19 Vasculopathy Study (ICVS). The work was also supported by a philanthropic grant from the 3M Foundation to RCSI University of Medicine and Health Sciences in support of COVID-19 research.
“Understanding the root cause of a disease is the first step toward developing effective treatments,” said Professor James O’Donnell, Director of the Irish Centre for Vascular Biology, RCSI and Consultant Haematologist in the National Coagulation Centre in St James’s Hospital, Dublin.
“Millions of people are already dealing with the symptoms of Long COVID syndrome, and more people will develop Long COVID as the infections among the unvaccinated continue to occur. It is imperative that we continue to study this condition and develop effective treatments.”
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The United States recently secured 1.7 million doses of a compound that could help to treat Covid-19 patients. In preliminary studies, Molnupiravir reduced the transmission of the Sars-CoV-2 coronavirus. Researchers at the Max Planck Institute for Biophysical Chemistry in Göttingen and the Julius Maximilians University Würzburg have now elucidated the underlying molecular mechanism. The antiviral agent incorporates RNA-like building blocks into the RNA genome of the virus. If this genetic material is further replicated, defective RNA copies are produced and the pathogen can no longer spread. Molnupiravir is currently being tested in clinical trials.
Since the onset of the coronavirus pandemic, numerous scientific projects set out to investigate measures against the new virus. At full stretch, researchers are developing various vaccines and drugs — with different degrees of success. Last year, the antiviral drug Remdesivir gained attention when it became the first drug against Covid-19 to be approved. Studies, including work by Patrick Cramer at the Max Planck Institute for Biophysical Chemistry in Göttingen and Claudia Höbartner at the Julius Maximilians University Würzburg (Germany), showed why the drug has a rather weak effect on the virus.
Molnupiravir, another antiviral drug candidate, was originally developed to treat influenza. Based on preliminary clinical trials, the compound promises to be highly effective against Sars-CoV-2. “Knowing that a new drug is working is important and good. However, it is equally important to understand how Molnupiravir works at the molecular level in order to gain insights for further antiviral development,” Max Planck Director Cramer explains. “According to our results, Molnupiravir acts in two phases.”
Mutations in the genome stop the virus
Molnupiravir is an orally available drug which becomes activated through metabolization in the body. When it enters the cell, it is converted into RNA-like building blocks. In the first phase, the viral copying machine, called RNA polymerase, incorporates these building blocks into the RNA genome of the virus. However, unlike Remdesivir, which slows down the viral RNA polymerase, Molnupiravir does not directly interfere with the function of the copying machine. Instead, in the second phase, the RNA-like building blocks connect with the building blocks of the viral genetic material. “When the viral RNA then gets replicated to produce new viruses, it contains numerous errors, so-called mutations. As a result, the pathogen can no longer reproduce,” says Florian Kabinger, a doctoral student in Cramer’s department. Together with the other first authors, Carina Stiller and Jana Schmitzová, he conducted the crucial experiments for the study.
Molnupiravir also appears to trigger mutations in other RNA viruses, preventing them from spreading further. “The compound could potentially be used to treat a whole spectrum of viral diseases,” tells Höbartner, a professor of chemistry at the University of Würzburg. “Molnupiravir has a lot of potential.” Currently, the promising drug candidate is in phase III studies, where it is being tested on a large number of patients. Whether Molnupiravir is safe to be approved as a drug will probably be announced in the second half of the year. The U.S. government is already optimistic and has recently secured about 1.7 million doses worth more than a billion dollars.
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Materials provided by Max-Planck-Gesellschaft. Note: Content may be edited for style and length.

For the more than 5 million people in the world who have undergone an upper-limb amputation, prosthetics have come a long way. Beyond traditional mannequin-like appendages, there is a growing number of commercial neuroprosthetics — highly articulated bionic limbs, engineered to sense a user’s residual muscle signals and robotically mimic their intended motions.
But this high-tech dexterity comes at a price. Neuroprosthetics can cost tens of thousands of dollars and are built around metal skeletons, with electrical motors that can be heavy and rigid.
Now engineers at MIT and Shanghai Jiao Tong University have designed a soft, lightweight, and potentially low-cost neuroprosthetic hand. Amputees who tested the artificial limb performed daily activities, such as zipping a suitcase, pouring a carton of juice, and petting a cat, just as well as — and in some cases better than — those with more rigid neuroprosthetics.
The researchers found the prosthetic, designed with a system for tactile feedback, restored some primitive sensation in a volunteer’s residual limb. The new design is also surprisingly durable, quickly recovering after being struck with a hammer or run over with a car.
The smart hand is soft and elastic, and weighs about half a pound. Its components total around $500 — a fraction of the weight and material cost associated with more rigid smart limbs.
“This is not a product yet, but the performance is already similar or superior to existing neuroprosthetics, which we’re excited about,” says Xuanhe Zhao, professor of mechanical engineering and of civil and environmental engineering at MIT. “There’s huge potential to make this soft prosthetic very low cost, for low-income families who have suffered from amputation.”
Zhao and his colleagues have published their work today in Nature Biomedical Engineering. Co-authors include MIT postdoc Shaoting Lin, along with Guoying Gu, Xiangyang Zhu, and collaborators at Shanghai Jiao Tong University in China.

Scientists at the National Institutes of Health (NIH) have developed a new sample preparation method to detect SARS-CoV-2, the virus that causes COVID-19. The method bypasses extraction of the virus’ genetic RNA material, simplifying sample purification and potentially reducing test time and cost. The method is the result of a collaboration among researchers at the National Eye Institute (NEI), the NIH Clinical Center (CC), and the National Institute of Dental and Craniofacial Research (NIDCR).
Diagnostic testing remains a crucial tool in the fight against the COVID-19 pandemic. Standard tests for detection of SARS-CoV-2 involve amplifying viral RNA to detectable levels using a technique called quantitative reverse transcription PCR (RT-qPCR). But first, the RNA must be extracted from the sample. Manufacturers of RNA extraction kits have had difficulty keeping up with demand during the COVID-19 pandemic, hindering testing capacity worldwide. With new virus variants emerging, the need for better, faster tests is greater than ever.
A team led by Robert B. Hufnagel, M.D., Ph.D., chief of the NEI Medical Genetics and Ophthalmic Genomic Unit, and Bin Guan, Ph.D., a fellow at the Ophthalmic Genomics Laboratory at NEI, used a chelating agent made by the lab supply company Bio-Rad called Chelex 100 resin to preserve SARS-CoV-2 RNA in samples for detection by RT-qPCR.
“We used nasopharyngeal and saliva samples with various virion concentrations to evaluate whether they could be used for direct RNA detection,” said Guan, the lead author of a report on the technique, which published this week in iScience. “The answer was yes, with markedly high sensitivity. Also, this preparation inactivated the virus, making it safer for lab personnel to handle positive samples.”
Hufnagel’s team made their discovery by testing a variety of chemicals using synthetic and human samples to identify those that could preserve the RNA in samples with minimal degradation while allowing direct detection of the virus by RT-qPCR.
To validate the test, NIDCR’s Blake M. Warner, D.D.S., Ph.D., M.P.H., and his team collected patient samples (on Research Protocol NIH IRB 20-D-0094) and stored them in either viral transport media, or the newly developed chelating-resin-buffer at the NIH Symptomatic Testing Facility.
The samples in viral transport media were tested by the COVID-19 testing team at NIH’s Clinical Center, led by Karen M. Frank, M.D., Ph.D., using conventional RNA extraction and RT-qPCR testing. The samples in the chelating-resin-buffer were heated and the viral RNA was, then, tested by RT-qPCR. The new preparation significantly increased the RNA yield available for testing, compared to the standard method.
“We think this novel methodology has clear benefits of increasing sensitivity, cost and time savings for testing,” said Hufnagel, “The method stabilizes the RNA at room temperature for easier transport, storage, and handling in clinical settings.”
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Materials provided by NIH/National Eye Institute. Note: Content may be edited for style and length.

Supportive social interactions in adulthood are important for your ability to stave off cognitive decline despite brain aging or neuropathological changes such as those present in Alzheimer’s disease, a new study finds.
In the study publishing August 16 in JAMA Network Open, researchers observed that simply having someone available most or all of the time whom you can count on to listen to you when you need to talk is associated with greater cognitive resilience — a measure of your brain’s ability to function better than would be expected for the amount of physical aging- or disease-related changes in the brain, which many neurologists believe can be boosted by engaging in mentally stimulating activities, physical exercise, and positive social interactions.
“We think of cognitive resilience as a buffer to the effects of brain aging and disease,” says lead researcher Joel Salinas, MD, the Lulu P. and David J. Levidow Assistant Professor of Neurology at NYU Grossman School of Medicine and member of the Department of Neurology’s Center for Cognitive Neurology. “This study adds to growing evidence that people can take steps, either for themselves or the people they care about most, to increase the odds they’ll slow down cognitive aging or prevent the development of symptoms of Alzheimer’s disease — something that is all the more important given that we still don’t have a cure for the disease.”
An estimated 5 million Americans are living with Alzheimer’s disease, a progressive condition that affects mostly those over 65 and interferes with memory, language, decision-making, and the ability to live independently. Salinas says that while the disease usually affects an older population, the results of this study indicate that people younger than 65 would benefit from taking stock of their social support. For every unit of decline in brain volume, individuals in their 40s and 50s with low listener availability had a cognitive age that was four years older than those with high listener availability.
“These four years can be incredibly precious. Too often we think about how to protect our brain health when we’re much older, after we’ve already lost a lot of time decades before to build and sustain brain-healthy habits,” says Salinas. “But today, right now, you can ask yourself if you truly have someone available to listen to you in a supportive way, and ask your loved ones the same. Taking that simple action sets the process in motion for you to ultimately have better odds of long-term brain health and the best quality of life you can have.”
Salinas also recommends that physicians consider adding this question to the standard social history portion of a patient interview: asking patients whether they have access to someone they can count on to listen to them when they need to talk. “Loneliness is one of the many symptoms of depression, and has other health implications for patients,” says Salinas. “These kinds of questions about a person’s social relationships and feelings of loneliness can tell you a lot about a patient’s broader social circumstances, their future health, and how they’re really doing outside of the clinic.”
How the Study Was Conducted
Researchers used one of the longest running and most closely monitored community-based cohorts in the U.S., the Framingham Heart Study (FHS), as the source of their study’s 2,171 participants, with an average age of 63. FHS participants self-reported information on the availability of supportive social interactions including listening, good advice, love and affection, sufficient contact with people they’re close with, and emotional support.
Study participants’ cognitive resilience was measured as the relative effect of total cerebral brain volume on global cognition, using MRI scans and neuropsychological assessments taken as part of the FHS. Lower brain volumes tend to associate with lower cognitive function, and in this study, researchers examined the modifying effect of individual forms of social support on the relationship between cerebral volume and cognitive performance.
The cognitive function of individuals with greater availability of one specific form of social support was higher relative to their total cerebral volume. This key form of social support was listener availability and it was highly associated with greater cognitive resilience.
Researchers note that further study of individual social interactions may improve understanding of the biological mechanisms that link psychosocial factors to brain health. “While there is still a lot that we don’t understand about the specific biological pathways between psychosocial factors like listener availability and brain health, this study gives clues about concrete, biological reasons why we should all seek good listeners and become better listeners ourselves,” says Salinas.
In addition to Salinas, researchers from the Boston University School of Medicine, Harvard Medical School, the McCance Center for Brain Health at Massachusetts General Hospital, the Turner Institute for Brain and Mental Health at Monash University, the Harvard TH Chan School of Public Health, the Boston University School of Public Health, the University of California Davis, and the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at the University of Texas Health Sciences Center San Antonio were also involved in the study.

A gene called PfAP2-HS allows the malaria parasite to defend itself from adverse conditions in the host, including febrile temperatures, according to a new study led by the Barcelona Institute for Global Health (ISGlobal), an institution supported by “la Caixa” Foundation. The study, published in Nature Microbiology, resolves a long-standing question on how the parasite responds to changes in its environment.
Infection by Plasmodium falciparum, which causes one of the most severe forms of malaria in humans, is characterised by periodic fevers (each time a cycle of asexual reproduction is completed and parasites are released into the blood stream). This is because fever is an important element in our body’s response against pathogens, since it affects the stability of cellular proteins and helps reduce parasite burden. In turn, most organisms have a defence mechanism against increased temperatures: the expression of heat-shock proteins (HSP), which act as chaperones.
“In most of the eukaryotic organisms, from yeasts to mammals, the expression of these proteins depends on a highly conserved transcription factor called HSF1,” explains Alfred Cortés, ICREA researcher at ISGlobal and study coordinator. “However, malaria parasites — which are also eukaryotes — lack the HSF1 gene, although we know that they can survive at febrile temperatures,” he adds.
In this study, Cortés and his team set out to investigate how the malaria parasite regulates its response to higher temperatures (or heat shock) despite the absence of HSF1. They observed that a P. falciparum cell line, grown in the laboratory, had lost its capacity to survive when exposed to a temperature of 41.5ºC, and that this was due to a mutation in a gene which they named PfAP2-HS. They showed that PfAP2-HS acts as a transcription factor that activates the expression of heat shock proteins hsp70-1 and hsp90 by binding to their respective promoters (i.e. the “on-off button” of a gene). They also showed that engineered parasites lacking the PfAP2-HS gene not only had a lower survival when exposed to higher temperatures, but also showed reduced growth at “normal” temperatures of 37ºC.
“This means that, in addition to its role in the protective heat-shock response, PfAP2-HS is also important for maintaining protein stability in the parasite at basal temperatures,” says Elisabet Tintó-Font, first author of the study. Moreover, absence of PfAP2-HS in P. falciparum led to a higher susceptibility of the parasite to the antimalarial drug artemisinin, due to alterations in protein balance.
The research team found homologues of PfAP2-HS in all Plasmodium species analysed, even in those that infect mice and do not cause fever. “This suggests that, at least in those species, the response orchestrated by AP2-HS could protect against other adverse conditions in the host,” says Cortés. “This is the first transcription factor described in Plasmodium capable of regulating responses to adverse host conditions, including fever. PfAP2-HS acts as “an orchestra director,” coordinating the other proteins involved in the response,” he adds.
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Materials provided by Barcelona Institute for Global Health (ISGlobal). Note: Content may be edited for style and length.

Preterm birth has been shown to increase the risk of autism spectrum disorders and other developmental problems, particularly in males. The more premature a baby is, the greater the risk of either motor or cognitive deficits. What does the preterm baby lose that is so critical to long-term outcomes?
A new study, in mice, suggests that one factor may be the loss of a placental hormone that the developing brain would normally see in the second half of pregnancy.
The study is the first to provide direct evidence that loss of a placental hormone alters long-term brain development.
In the study, researchers in the laboratory of Anna Penn, MD, PhD, now at Columbia University Vagelos College of Physicians and Surgeons and previously at Children’s National Hospital in Washington, D.C., found that reducing amounts of a single hormone, called allopregnanolone(ALLO), in the placenta caused brain and behavior changes in male offspring that resemble changes seen in some people with autism spectrum disorder.
The study also found that both brain structure and behavioral changes in the mice could be prevented with a single injection of ALLO in late pregnancy.
“Our study provides new and intriguing insights into how the loss of placental hormones — which happens in preterm birth or if the placenta stops working well during pregnancy — can lead to long-term structural changes in the brain that increase the risk for autism or other neuropsychiatric disorders,” says lead author Claire-Marie Vacher, PhD, assistant professor of neonatal sciences in the Department of Pediatrics at Columbia University’s Vagelos College of Physicians and Surgeons. “What’s encouraging is that these disorders may be preventable if diagnosed and treated early.”
The study was published online August 16 in the journal Nature Neuroscience.

People who work night shifts are at increased risk of developing an irregular and often abnormally fast heart rhythm called atrial fibrillation (AF), according to research published in the European Heart Journal.
The study is the first to investigate the links between night shift work and AF. Using information from 283,657 people in the UK Biobank database, researchers found that the longer and more frequently that people worked night shifts over their lifetimes, the greater their risk of AF. Night shift work was also linked to an increased risk of heart disease, but not to stroke or heart failure.
In addition, the researchers, led by Professor Yingli Lu, of Shanghai Ninth People’s Hospital and Shanghai JiaoTong University School of Medicine, Shanghai, China, and Professor Lu Qi, of Tulane University School of Public Health and Tropical Medicine, New Orleans, USA, investigated whether genetic predisposition to AF could play a role in the increased risk. They evaluated the overall genetic risk on the basis of 166 genetic variations known to be associated with the condition but found that the genetic risk levels did not affect the link between working night shifts and AF risk, regardless of whether participants had a low, medium or high genetic risk.
Prof. Lu said: “Although a study like this cannot show a causal link between night shifts and atrial fibrillation and heart disease, our results suggest that current and lifetime night shift work may increase the risk of these conditions.
“Our findings have public health implications for preventing atrial fibrillation. They suggest that reducing both the frequency and the duration of night shift work may be beneficial for the health of the heart and blood vessels.”
The study included 286,353 people who were in paid employment or self-employed. A total of 283,657 of these participants did not have AF when they enrolled in UK Biobank, and 276,009 did not have heart failure or stroke. Information on genetic variants was available for 193,819 participants without AF, and 75,391 of them answered in-depth questions about their lifetime employment in a questionnaire sent out in 2015. Among the participants free of heart disease and stroke when they joined the study, 73,986 provided information on their employment history. During an average follow-up time of over ten years, there were 5,777 AF cases.

There are a number of simple, practical steps that families can take — including reducing passive screen time and news consumption, having a structured daily schedule and getting enough sleep — that can promote resilience against mental health problems in youth during the COVID-19 pandemic, according to a new study published this week in the open-access journal PLOS ONE by Maya Rosen of Harvard University, US, and colleagues.
The COVID-19 pandemic has introduced unprecedented change into the lives of children and adolescents. Many of these disruptions, coupled with pandemic-related stressors, are likely to increase risk for depression, anxiety and behavioral problems in youth.
In the new study, researchers recruited participants from two ongoing longitudinal studies of children and adolescents in the greater Seattle area. 224 youth and their caregivers completed an initial questionnaire assessing social behaviors, psychopathology and pandemic-related stressors in April and May 2020; 184 of these youth and their caregivers completed a similar battery of assessments six months later, in November 2020 through January 2021. Since data on each youth was available from prior to the pandemic, results at each time point could be controlled for pre-pandemic symptoms. The youth ranged in age from 7 to 15 years old, were 47.8% female, and their racial and ethnic background reflected the Seattle are, with 66% of participants White, 11% Black, 11% Asian and 8% Hispanic or Latino.
The number of pandemic-related stressors was strongly associated with increases in both internalizing (β=0.345, p

Among individuals who survive a trauma that resulted in the loss of a close friend or loved one, symptoms of post-traumatic stress disorder can predict complicated grief — a sense of persistent sadness and an inability to cope — years after the trauma, according to research published by the American Psychological Association.
“Grief is a normal response to the loss of someone close, but traumatic losses may severely harm survivors for years,” said Kristin Alve Glad, PhD, a researcher at the Norwegian Centre for Violence and Traumatic Stress Studies and lead author of the study. “Our findings suggest that when treating trauma survivors, targeting symptoms of PTSD early might help them avoid complicated grief later on.”
For most people who experience grief, feelings of distress and bereavement tend to diminish over time, according to Glad. In the case of complicated grief, instead of fading, symptoms can often linger or worsen and can impair or prevent people from living their normal lives.
“Complicated grief has been defined as a persistent, intense yearning, longing and sadness, usually accompanied by insistent thoughts or images of the deceased and a sense of disbelief or an inability to accept the painful reality of the person’s death,” said Glad.
In the study, published in the journal Psychological Trauma: Theory, Research, Practice and Policy, researchers interviewed survivors of a 2011 domestic terrorist attack on Utøya, an island in Norway, who lost someone close to them in the attack. Of the 275 participants, 256 lost a close friend, six lost a family member and 13 lost a close friend and a family member/partner.
Participants took part in individual, face-to-face interviews with experienced health care personnel three times following the attack on Utøya: 4-5 months, 14-15 months and 30-32 months after the attack. The interviews included questions about the post-traumatic stress symptoms and complicated grief reactions (e.g., trouble accepting the death of their loved one, interference of grief in their daily life, troubling thoughts relating to death, avoidance of reminders of the loss and feelings of isolation or distance from others).
Researchers found that participants who reported symptoms of PTSD were significantly more likely to report symptoms of complicated grief as well. They also found that participants who experienced early symptoms of PTSD a year after the attack experienced even greater symptoms of complicated grief years later.
“The fact that we found that PTSD symptoms predicted complicated grief reactions at a subsequent time point, but complicated grief did not predict the development of PTSD, is interesting, because it suggests that targeting PTSD symptoms may hinder later development of complicated grief,” said Glad. “This may have important implications for clinicians working with bereaved trauma survivors.”
The researchers believe that the effects of the terrorist attack on the survivors were particularly severe because they did not just lose a loved one — they were directly exposed to the attack as well. This dual burden of the unexpected loss and the survivors’ high exposure to trauma may result in a different trajectory of PTSD symptoms and complicated grief than for bereaved who are not directly exposed to the trauma.
These findings could apply to anyone who has lost a loved one in a potentially traumatizing way, according to Glad. Knowledge about the relationship between symptoms of PTSD and complicated grief over time may help clinicians develop more effective treatment strategies and formulate better treatment plans for the survivors who struggle the most to cope, the researchers said.