Publisher Health

The first large study showing that leisure time physical activity and occupational physical activity have opposite, and independent, associations with cardiovascular disease risk and longevity is published today in European Heart Journal, a journal of the European Society of Cardiology (ESC).
“We adjusted for multiple factors in our analysis, indicating that the relationships were not explained by lifestyle, health conditions or socioeconomic status,” said study author Professor Andreas Holtermann of the National Research Centre for the Working Environment, Copenhagen, Denmark.
The World Health Organization (WHO) recommends physical activity during both recreation and work to improve health.* Previous studies have suggested that occupational activity is related to an increased risk for heart disease and mortality but have been too small to fully explain whether this was due to the manual work or because employees had unhealthy lifestyles or low socioeconomic status (e.g. low level of education).
This study included 104,046 women and men aged 20-100 years from the Copenhagen General Population Study with baseline measurements in 2003-2014. Participants completed questionnaires about activity during leisure and employment and were categorised as low, moderate, high, or very high activity for each.
During a median follow-up of 10 years, there were 9,846 (9.5%) deaths from all causes and 7,913 (7.6%) major adverse cardiovascular events (MACE, defined as fatal and nonfatal myocardial infarction, fatal and non-fatal stroke, and other coronary death).
Compared to low leisure time physical activity, after adjustment for age, sex, lifestyle, health, and education, moderate, high, and very high activity were associated with 26%, 41%, and 40% reduced risks of early death, respectively. In contrast, compared to low work activity, high and very high activity were associated with 13% and 27% increased risks of death, respectively.

From 12 April people in England will be able to visit shops, gyms and hairdressers, as well as the outdoor spaces of pubs and restaurants.So with the next stages of lockdown easing on the horizon, how can you keep yourself and others safe from transmitting coronavirus in these new locations?The BBC’s science editor David Shukman explains the risks and what to look out for.Producers: Aisha Doherty and Kate StephensGraphics: Mel Lou

Victoria Spence, an influencer and life coach from Manchester, told the BBC she fell into a “deep, dark hole” about her body image as a teenager, leading to her developing an eating disorder. But when her parents tried to seek help, her doctor told her that her Body Mass Index (BMI) wasn’t low enough for treatment.A report released by the women and equalities committee has called for the BMI to be scrapped altogether. Victoria, who is now 26, shares her experiences with her disorder, and her path to recovery on social media, with the BBC.

New insights into the immune response to SARS-CoV-2 infections could bring better treatments for COVID-19 cases.
An international team of researchers unexpectedly found that a biochemical pathway, known as the immune complement system, is triggered in lung cells by the virus, which might explain why the disease is so difficult to treat. The research is published this week in the journal Science Immunology.
The researchers propose that the pairing of antiviral drugs with drugs that inhibit this process may be more effective. Using an in vitro model using human lung cells, they found that the antiviral drug Remdesivir, in combination with the drug Ruxolitinib, inhibited this complement response.
This is despite recent evidence that trials of using Ruxolitinib alone to treat COVID-19 have not been promising.
To identify possible drug targets, Majid Kazemian, assistant professor in the departments of computer science and biochemistry at Purdue University, said the research team examined more than 1,600 previously FDA-approved drugs with known targets.
“We looked at the genes that are up-regulated by COVID-19 but down-regulated by specific drugs, and Ruxolitinib was the top drug with that property,” he said.

After a year of virtual gathering, getting back to real-life relationships can be intimidating. These eight simple exercises can help.As we move through the spring of The Great Vaccination, many of us are feeling cautious optimism, and also its flip side: creeping dread.Maybe you have a sense of ambivalence about how to interact with others again. If you used to work in an office, you might be worried about returning to work — but eager to see people again. Or you find yourself having to confront a neighbor about a longstanding problem — but you’re out of practice with conflict resolution. (I’m not sure I remember how to talk to another human anymore, let alone one I disagree with.)Whatever the specifics, “there will be new forms of social anxiety, said Dacher Keltner, a professor of psychology and the director of the Social Interaction Lab at the University of California, Berkeley.“People are really anxious about being out in restaurants with friends, or about dancing with a big sweaty group of people — or even about sharing a yoga mat,” he said. “It’s always good to remember individual differences — there’s a lot of variability. But there will be a lasting societal legacy around intimacy, the noise that comes with returning to school, the complexity of the playground and of work.”Dr. Keltner has studied human behavior and the biological and evolutionary underpinnings of emotions for decades, with a focus on “pro-social” states — behavior that strengthens connections between individuals — that are especially good for society.“We’re hyper-social mammals — it’s our most signature strength,” said Dr. Keltner, a co-founder of the Greater Good Science Center who was also a scientific consultant on emotions for the Pixar film “Inside Out.” “It’s what sets us apart from other primates: We help, we laugh, we collaborate, we assist.”Lately, we’ve been living our lives siloed away online, missing many of the essential face-to-face experiences that are key to human interaction. It’s notable that Dr. Vivek Murthy, the newly reappointed U.S. Surgeon General, has talked not only about the physical and economic toll of the pandemic, but also of “the social recession.”Before Covid, this kind of post-isolation anxiety was most often suffered by people who re-enter the civilian world after prison, wartime deployment, humanitarian aid work or remote expeditions. The challenge now is that so many more of us will be experiencing some aspect of this all at once, and coming back to social situations with others who likely have their own fears too. It is stalled social development, on a societal level.Debra Kaysen, a clinical psychologist and a professor of psychiatry and behavioral sciences at Stanford University, said that coming back to so-called “civilian life” can be disorienting, surreal and difficult — and not just for combat veterans. Her clinical and research work focuses on anxiety disorders and trauma, and she has worked on developing coping strategies for health care workers dealing with mental health concerns during the pandemic.Now, everyone is trying to navigate conflicting threat levels in a way that used to be specific to those populations, she said. Cues that used to be neutral or positive, like being around other people (I love my friends and family!) are now associated with threat (my friends and family might infect me with Covid!). And we are confronting the challenge of how to turn off that alarm. “What’s a true alarm and what’s a false alarm has gotten more confusing for all of us,” Dr. Kaysen said.So how do we relearn how to be together?Give yourself permission to set small, achievable goals. And accept that other people are going to have different responses than you — the friend or family member who wants to eat inside the restaurant when you don’t, for example, or who is ready to get on a plane and take a vacation.Accept that certain activities may feel tough for awhile. Driving an hour to a meeting. Flying a red-eye to a conference. Attending a family reunion, say, or four pandemic-postponed weddings in one month.All of this can prompt you to ask, of your family or your boss or even yourself: “Is it really worth the time?” and “Now that I know things can be different, do I want to go back to my old life?”Recovering doesn’t mean you go back to the way you were before, Dr. Kaysen said, using kintsugi, the Japanese technique of repairing broken pottery with gold, as an analogy for coming out of hard times with awareness of the change, and stronger than before. “It’s that you create a new normal, one that’s functional and beautiful — and different.”Dr. Keltner agreed that we may need to “re-educate ourselves” — “like, how do we hug again?” Your timing might be off for a hug, or a joke or even a compliment. “How do you look someone in the eye so that it’s not intrusive? How do you compliment someone? You might not have done it for a year.”Rather than be overwhelmed by everything at once — for example, going to a party where you have to adjust to greeting acquaintances, eating with others and attempting to make small talk — all at the same time — why not take things step by step? This moment can be an opportunity.8 Exercises to Strengthen Your Social MusclesHere are eight small, science-based exercises Dr. Keltner recommends to help ease back into your community. Go at your own pace.Share food with someone.Eating a meal together boosts mood and is a potent antidote for loneliness — aiming for in-person interaction around the ritual of eating is a great goal, even if you don’t meet it every single day. An outdoor picnic or a distanced backyard happy hour is a great and safe option for reconnecting with friends and family.Tell someone a joke in person.You may be out of practice and have to work on your timing. But making eye contact and laughing together is essential to feeling connected to someone else — even if the joke falls flat, being silly together will feel really good.Ask someone what they’re listening to or reading right now.Music and literature can be a community-building gift. Listen to music together; exchange books and have an in-person discussion afterward. This is a social exercise, but also one that will give you a much-needed hit of novelty along with the insight.Reach out to someone you’ve lost touch with.Make a phone call, send a meaningful text, write an email. It’s time to start rebuilding the larger social infrastructure outside our immediate circles.Strike up a conversation with a stranger.Pick someone with whom you have passing contact: a fellow dog-walker, the cashier at a grocery store, a delivery person on your doorstep. Make eye contact; talk to each of them as a person rather than as a function. It’s so easy to ignore the human behind a mask. Make the effort to ask something outside the normal transaction — what’s changed since the last time you saw each other, what they’re looking forward to.Move with someone.Dance, walk, run, swim, bike — or even do the dishes and fold the laundry together. Physical synchronicity is one of the most important ways we have to connect with someone else.Sit quietly with someone …and remember how to comfortably be, without talking, in companionable silence, with someone else. Let the other person know it’s OK to not always fill the air. Nonverbal communication is important to practice — and it’s a way to deepen your relationship.Make a date for the future.Think of something fun to do with someone you love — it could be a summer beach weekend, or maybe a ski trip next winter. Having something to look forward to is essential for well-being. Practice optimism, in anticipation of normalcy. Plan with hope.Bonnie Tsui’s books include “Why We Swim” and “The Uncertain Sea.”

Modern humans are fundamentally different from our closest living relatives, the great apes: We live on the ground, walk on two legs and have much larger brains. The first populations of the genus Homo emerged in Africa about 2.5 million years ago. They already walked upright, but their brains were only about half the size of today’s humans. These earliest Homo populations in Africa had primitive ape-like brains — just like their extinct ancestors, the australopithecines. So when and where did the typical human brain evolve?
CT comparisons of skulls reveal modern brain structures
An international team led by Christoph Zollikofer and Marcia Ponce de León from the Department of Anthropology at the University of Zurich (UZH) has now succeeded in answering these questions. “Our analyses suggest that modern human brain structures emerged only 1.5 to 1.7 million years ago in African Homo populations,” Zollikofer says. The researchers used computed tomography to examine the skulls of Homo fossils that lived in Africa and Asia 1 to 2 million years ago. They then compared the fossil data with reference data from great apes and humans.
Apart from the size, the human brain differs from that of the great apes particularly in the location and organization of individual brain regions. “The features typical to humans are primarily those regions in the frontal lobe that are responsible for planning and executing complex patterns of thought and action, and ultimately also for language,” notes first author Marcia Ponce de León. Since these areas are significantly larger in the human brain, the adjacent brain regions shifted further back.
Typical human brain spread rapidly from Africa to Asia
The first Homo populations outside Africa — in Dmanisi in what is now Georgia — had brains that were just as primitive as their African relatives. It follows, therefore, that the brains of early humans did not become particularly large or particularly modern until around 1.7 million years ago. However, these early humans were quite capable of making numerous tools, adapting to the new environmental conditions of Eurasia, developing animal food sources, and caring for group members in need of help.
During this period, the cultures in Africa became more complex and diverse, as evidenced by the discovery of various types of stone tools. The researchers think that biological and cultural evolution are probably interdependent. “It is likely that the earliest forms of human language also developed during this period,” says anthropologist Ponce de León. Fossils found on Java provide evidence that the new populations were extremely successful: Shortly after their first appearance in Africa, they had already spread to Southeast Asia.
Brain imprints in fossil skulls reveal evolution of humans
Previous theories had little to support them because of the lack of reliable data. “The problem is that the brains of our ancestors were not preserved as fossils. Their brain structures can only be deduced from impressions left by the folds and furrows on the inner surfaces of fossil skulls,” says study leader Zollikofer. Because these imprints vary considerably from individual to individual, until now it was not possible to clearly determine whether a particular Homo fossil had a more ape-like or a more human-like brain. Using computed tomography analyses of a range of fossil skulls, the researchers have now been able to close this gap for the first time.
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The millions of people who have chronic sinusitis deal not only with stuffy noses and headaches, they also commonly struggle to focus, and experience depression and other symptoms that implicate the brain’s involvement in their illness.
New research links sinus inflammation with alterations in brain activity, specifically with the neural networks that modulate cognition, introspection and response to external stimuli.
The paper was published today in JAMA Otolaryngology-Head & Neck Surgery.
“This is the first study that links chronic sinus inflammation with a neurobiological change,” said lead author Dr. Aria Jafari, a surgeon and assistant professor of Otolaryngology-Head & Neck Surgery at the University of Washington School of Medicine.
“We know from previous studies that patients who have sinusitis often decide to seek medical care not because they have a runny nose and sinus pressure, but because the disease is affecting how they interact with the world: They can’t be productive, thinking is difficult, sleep is lousy. It broadly impacts their quality of life. Now we have a prospective mechanism for what we observe clinically.”
Chronic rhinosinusitis affects about 11% of U.S. adults, according to the Centers for Disease Control and Prevention. The condition can necessitate treatment over a span of years, typically involving antibiotics. Repeated cycles of inflammation and repair thicken sinus tissues, much like calloused skin. Surgery may resolve the issue, but symptoms also can recur.

New research has uncovered a surprising role for so-called “jumping” genes that are a source of genetic mutations responsible for a number of human diseases. In the new study from Children’s Medical Center Research Institute at UT Southwestern (CRI), scientists made the unexpected discovery that these DNA sequences, also known as transposons, can protect against certain blood cancers.
These findings, published in Nature Genetics, led scientists to identify a new biomarker that could help predict how patients will respond to cancer therapies and find new therapeutic targets for acute myeloid leukemia (AML), the deadliest type of blood cancer in adults and children.
Transposons are DNA sequences that can move, or jump, from one location in the genome to another when activated. Though many different classes of transposons exist, scientists in the Xu laboratory focused on a type known as long interspersed element-1 (L1) retrotransposons. L1 sequences work by copying and then pasting themselves into different locations in the genome, which often leads to mutations that can cause diseases such as cancer. Nearly half of all cancers contain mutations caused by L1 insertion into other genes, particularly lung, colorectal, and head-and-neck cancers. The incidence of L1 mutations in blood cancers such as AML is extremely low, but the reasons why are poorly understood.
When researchers screened human AML cells to identify genes essential for cancer cell survival, they found MPP8, a known regulator of L1, to be selectively required by AML cells. Curious to understand the underlying basis of this connection, scientists in the Xu lab studied how L1 sequences were regulated in human and mouse leukemia cells. They made two key discoveries. The first was that MPP8 blocked the copying of L1 sequences in the cells that initiate AML. The second was that when the activity of L1 was turned on, it could impair the growth or survival of AML cells.
“Our initial finding was a surprise because it’s been long thought that activated transposons promote cancer development by generating genetic mutations. We found it was the opposite for blood cancers, and that decreased L1 activity was associated with worse clinical outcomes and therapy resistance in patients,” says Jian Xu, Ph.D., associate professor in CRI and senior author of the study.
MPP8 thus suppressed L1 in order to safeguard the cancer cell genome and allow AML-initiating cells to survive and proliferate. Cancer cells, just like healthy cells, need to maintain a stable genome to replicate. Too many mutations, like those created by L1 activity, can impair the replication of cancer cells. Researchers found L1 activation led to genome instability, which in turn activated a DNA damage response that triggered cell death or eliminated the cell’s ability to replicate itself. Xu believes this discovery may provide a mechanistic explanation for the unusual sensitivity of myeloid leukemia cells to DNA damage-inducing therapies that are currently used to treat patients.
“Our discovery that L1 activation can suppress the survival of certain blood cancers opens up the possibility of using it as a prognostic biomarker, and possibly leveraging its activity to target cancer cells without affecting normal cells,” says Xu.
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Researchers at the Francis Crick Institute have found that blocking a specific protein could increase tumour sensitivity to treatment with PARP inhibitors. Their work published in Science , suggests combining treatments could lead to improved therapy for patients with inheritable breast cancers.
Some cancers, including certain breast, ovarian and prostate tumours, are caused by a fault in the BRCA1 or BRCA2 genes, which are important for DNA repair. Treatment for these cancers has greatly improved thanks to the discovery of PARP inhibitors, drugs which capitalise on this weakness in the cancer as they block a back-up repair mechanism. This means the cancer cells cannot repair breaks in their DNA, which stops the tumour from growing.
However, in many cases, the cancer eventually develops resistance to this treatment and the tumour starts to regrow aggressively. Finding new ways to effectively kill cancer cells before this resistance develops, or re-sensitise them to treatment, is crucial to offer patients an improved chance of survival.
In their study, the research team used human cells to screen for proteins that affect their sensitivity to PARP inhibitor drugs. They found that blocking a protein, DNPH1, sensitised BRCA-defective cancer cells to treatment with the PARP inhibitor, leading to cell death in the laboratory.
Importantly, cells that had acquired resistance to the PARP inhibitor were killed when this protein was also blocked. And, as the combination did not affect healthy cells, this discovery suggests that DNPH1 is a promising target for future drug development.
Stephen West, lead author and group leader of the DNA Recombination and Repair Laboratory at the Crick says: “PARP inhibitors were a great breakthrough in the treatment of certain cancers, extending the lives of many people. However, patients have to take these drugs for the rest of their lives which sadly gives most tumours time to mutate and eventually develop resistance.
“We want to improve treatments for these patients by finding a way to strengthen PARP inhibitors so they completely kill the cancer. While more work needs to be done, in the lab and then in clinical trials, we’ve found a really promising potential treatment combination.”
In further experiments, the researchers characterised the role of the DNPH1 protein. It acts as a ‘scavenger’, removing faulty nucleotides from the pool of nucleotides which are used to build DNA. Without this process, this nucleotide ‘junk’ is incorporated into strands of DNA. The incorporation of faulty nucleotides is the key determinant that makes the cells more susceptible to the effects of PARP inhibitors.
Kasper Fugger, lead author and postdoc in the DNA Recombination and Repair Laboratory at the Crick says: “By investigating the function of DNPH1 and finding the molecules it interacts with, we have a good understanding of how the protein works in cells. This knowledge should help us to more effectively kill cancer cells by developing an inhibitor drug, which is specific enough to be used safely in people.”
The researchers are now collaborating with pharmaceutical companies to develop an inhibitor of the DNPH1 protein which, if shown to be safe and effective in clinical trials, could be used alongside PARP inhibitors as a cancer treatment.
The topic of DNA repair in cancer was the focus of a virtual conference, Medicine at the Crick, held in February. The event was part of a series which showcases major advances in biomedical science and brings together lab-based scientists together and clinicians to consider the potential impact on patient treatment.
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Two studies published in the open-access journal PLOS Pathogens provide new evidence supporting an important role for the immune system in shaping the evolution of SARS-CoV-2, the virus that causes COVID-19. These findings — and the novel technology behind them — improve understanding of how new SARS-CoV-2 strains arise, which could help guide treatment and vaccination efforts.
For the first study, Rachel Eguia of Fred Hutchinson Cancer Research Center in Seattle, Washington, and colleagues sought to better understand SARS-CoV-2 by investigating a closely related virus that has circulated widely for a far longer period of time: the common-cold virus 229E.
229E and SARS-CoV-2 are both in the coronavirus family, which features a “spike protein” that enables infection of human cells. A person who is infected with 229E develops an immune response against the spike protein that protects them from reinfection, but only for a few years. Whether reinfection then occurs because the immune response wears off or because 229E evolves to escape it has been unclear.
Eguia and colleagues addressed this question by testing the activity of serum samples collected from patients in the 1980s-90s against spike proteins from both old 229E strains and strains that evolved later on. They found that the old spike proteins were vulnerable to the older sera. However, modern spike proteins were able to evade older sera while remaining vulnerable to sera from modern patients.
This analysis suggests that modern strains of 229E have accumulated spike protein mutations that enable them to evade older sera. These findings raise the possibility that SARS-CoV-2 and other coronaviruses could undergo similar evolution, and that COVID-19 vaccines may require periodic updates to remain effective against new strains.
The authors add, “The human common-cold coronavirus evolves over the span of years to decades to erode neutralization by human polyclonal serum antibodies. This work suggests that human coronaviruses undergo significant antigenic evolution that may contribute to eventual re-infections.”
For the second study, Sung Hee Ko of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, and colleagues developed new technology for genetic sequencing of the SARS-CoV-2 spike protein, enabling detection of multiple SARS-CoV-2 strains that may be present at the same time within a single infected patient.
Previous studies have used standard sequencing methods to produce a single genetic sequence from an individual patient, obscuring the potential presence of multiple SARS-CoV-2 strains. By contrast, the new technology highlights virus diversity within each patient and enables tracking of the evolution of new SARS-CoV-2 strains during acute infection.
Indeed, when the researchers applied the new method to human respiratory samples, they found new SARS-CoV-2 variants arising within the same patient over the course of acute infection. The precise mutations in these variants suggest that they arose in response to selective pressure from the immune system.
Future application of the new technology could improve understanding of how the evolution of new SARS-CoV-2 variants within a single patient impacts their outcomes. The findings also suggest that patients might see greater benefits from early treatment with antiviral drugs capable of targeting multiple strains, than from delayed treatment with a single antiviral drug.
The authors add, “We used new technology to show that coronavirus variants with mutated spike proteins can arise early in the course of infection. Our results suggest more virus evolution in each person than previously thought, with potential implications for clinical outcomes and for the emergence of transmissible variant strains.”
Together, these two studies deepen understanding of how new SARS-CoV-2 strains arise in response to immune system activity, potentially paving the way for additional research and improved treatment.
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