Publisher Health

LMU scientists have investigated how most people’s immune defenses are able to curb the coronavirus so effectively that pneumonia does not occur.
The immune defenses of most people are able to curtail the spread of the SARS-CoV-2 virus in the body so effectively that they do not get pneumonia. But researchers have been largely at a loss to explain how exactly the invader is contained in the upper respiratory tract. Scientists at LMU’s University of Munich Hospital led by Dr. med. Kami Pekayvaz, Alexander Leunig, Associate Professor Dr. med. Konstantin Stark, and Dr. med. Leo Nicolai, working in cooperation with other research institutions, have discovered that patients with mild disease courses had a specific, effective antiviral upregulation of so-called interferon-stimulated genes. The team’s results have been published in the journal Nature Communications.
According to current research, 90 percent of infected persons are able to successfully ward off SARS-CoV-2 such as to prevent a severe course with infection of the lungs. To find out why this is the case, the team investigated blood samples and nasal swabs from over 100 patients — and did so using various methods for the analysis of genes, proteins, and other molecules that play a role in an immune response. They combined their findings with existing clinical data. Investigating patient samples over the entire course of the disease was the main focus of the study. First, the researchers closely monitored and analyzed a cohort of patients with risk factors for a severe course of the disease, distinguishing patients with and without pulmonary involvement. The findings obtained in this way were then validated in a large cohort of outpatients with mild courses of the disease.
“We discovered that early on in the disease, patients who had hardly any or no symptoms at all exhibited a very strong antiviral response in the immune cells in the blood,” say the authors from the Medical Clinic and Polyclinic I located in the Munich district of Großhadern. The response is characterized by upregulation of interferon-stimulated genes (ISGs). “You can picture these as a whole arsenal of proteins that cells can use against viral intruders,” explain the authors. “We think that this type of immune response prevents further spread of the virus, as the body is put on alert, meaning for example that the lung tissue is prepared for the intruder.” Moreover, in mild cases so-called natural killer cells and T cells seem to be less aggressive towards other cells. This probably prevents the body’s own cells becoming damaged. Finally, there was also an anti-inflammatory monocyte signature characteristic of a protective response.
In summary, the researchers say they have found a “specific immunological signature” that can prevent the SARS-CoV-2 virus from spreading in the body. Interestingly, this immune response is initially independent of antibodies, as they are produced later in the course of the illness.
“One goal now would be to modulate the immune system of high-risk patients or of individuals after viral exposition to activate these antiviral mechanisms,” say the authors. And: “Approaches already exist towards this — for example, nasal sprays have been used that trigger such a response via interferon alfa or other mechanisms.” These approaches should now be optimized, urge the authors, noting that such promising strategies could also prove helpful in the next pandemic against other viral pathogens than SARS-CoV-2.
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Materials provided by Ludwig-Maximilians-Universität München. Note: Content may be edited for style and length.

A team led by scientists at the University of Birmingham has come a step closer to uncovering the purpose of a distinctive set of modifications found at the beginning of messenger RNA which have long remained a fundamental mystery in molecular biology.
Messenger RNAs (mRNAs) are vital for protein production. Their specific structure at the beginning of the chain, called a cap, has two main functions. It protects the mRNA from breaking down, but also it plays a key role in the way the messenger RNA produces proteins.
In addition to the cap structure, the first few nucleotides of an mRNA can carry small decorations called methylation. These occur in animals as well as in some of their parasites like SARS viruses and trypanosomes, but their purpose has remained enigmatic.
Although scientists have known about these mRNA modification for more than 45 years, its effect on the function of mRNA has not been well understood. This is because scientists have not been able to show what happens when this methylation in mRNA is ‘knocked out’, or removed from animal model organisms.
In a new study, published in Nature Communications, researchers from the Universities of Birmingham, Oxford, Nottingham and Warwick succeeded in creating a knockout model using fruit flies (Drosophila) by removing two key genes. That means they were able to show what happens when the flies don’t have the two enzymes used in the methylation process.
They found that, although the modified flies did still live, the two enzymes played an important role in the animals’ reward learning process. These flies showed a defect in their ability to learn the association of a specific odour with a sugar reward.

A treatment strategy using an antibody that inhibits a cell signalling protein called interleukin-11 (IL-11) could lead to new hope for people with a debilitating genetic kidney disease called Alport syndrome. Scientists from Duke-NUS Medical School, Singapore, reported these findings in the Journal of the American Society of Nephrology.
Alport syndrome is an inherited genetic condition that affects approximately one in every 50,000 newborns globally. The gene mutations linked to this syndrome lead to abnormal collagen formation in certain tissues, affecting kidney function, hearing and eyesight. Chronic kidney failure can eventually result, due to damage and scar tissue formation in the glomerulus, the filtering unit of the kidney responsible for removing toxins while retaining important proteins.
Currently, there are no curative treatments for the condition. Instead, doctors attempt to reduce the rate of kidney damage with angiotensin-converting enzyme inhibitors (ACEi). These drugs lower blood pressure and reduce leakage of protein into the urine. However, many individuals with Alport Syndrome progress to end-stage kidney failure despite treatment with ACEi.
Lead author of the study, Dr Anissa Widjaja, an assistant professor with Duke-NUS’ Cardiovascular & Metabolic Disorders (CVMD) Programme, said, “Together with our collaborators in Singapore and Germany, we wanted to find out if IL-11 played a role in Alport syndrome disease development. This cell signalling protein had recently been implicated by other research in kidney scarring and dysfunction.”
Using a mouse model of Alport syndrome in humans, the team found that IL11 levels began to rise in the test animals by six weeks of age causing damage to glomerular cells that make up the filtering sieve lying between the incoming blood and the outgoing urine.
“We also found that administration of anti-IL11 therapies, in the form of an antibody drug, has beneficial effects in reducing the severity of Alport syndrome in the mice,” Asst Prof Widjaja and Professor Stuart Cook, the senior author of the study, elaborated. “This happened by reducing kidney injury, inflammation and scarring. Importantly, combining ACEi and anti-IL11 therapies increased the lifespan of Alport syndrome mice by more than 400 per cent relative to those that were treated with an ACEi drug alone.”
Professor Thomas Coffman, dean of Duke-NUS Medical School and a senior co-author of the study, commented, “This discovery spells new hope for treatment in Alport syndrome — not just to arrest the progress of the disease, but even to restore lost kidney function. Also, the study suggests that anti-IL11 therapeutics can have additive effects with ACEi treatment, enhancing its potential utility in the clinical arena.”
Asst Prof Widjaja and her colleagues are continuing their research by investigating whether anti-IL11 therapies can reverse kidney failure by promoting tissue regeneration.
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Metastatic cells form in a primary tumour and then break away from it, migrate to other organs, attach to them and form new tumours. This spread reduces patients’ chances of recovery. Scientists at the University of Geneva (UNIGE) have discovered some of the mechanisms by which these cells arise. This is due to cells that have narrowly escaped cell death (apoptosis) following a chemotherapeutic treatment. Those cells reprogram themselves to acquire metastatic skills. Thanks to this study, these cells — called PAME by the researchers — now appear as new therapeutic targets. These results can be read in the journal Cell Reports.
Metastatic cells occur in many forms of cancer. They originate in primary tumours and then break away and migrate. They travel through the tissues surrounding them, through blood vessels or lymphatic channels. Along the way, they may attach to one or more organs — such as the lungs, brain, bones or liver — and form new tumours also called metastases. This spread of the disease can negatively affect a patient’s chances of recovery.
Previous studies have identified metastatic cells during migration. It is also known that certain treatments can induce them. However, the precise mechanisms of their development remain a mystery. “We don’t know why, at a given moment, certain cells separate from the primary tumour,” explains Ariel Ruiz i Altaba, a Full Professor in the Department of Genetic Medecine and Development at the UNIGE Faculty of Medicine. “The phenomenon is difficult to analyze because, before they migrate, there is nothing to distinguish future metastatic cells, or pro-metastatic cells, from other cells within the tumour.”
Cells that should have died
Professor Ruiz i Altaba’s team composed of two postdocs for this study, Arwen Conod (first author) and Marianna Silvano, has now provided some answers. Thanks to a recent research, these UNIGE scientists have discovered that the experience of imminent death within the primary tumour pushes certain cells to acquire pro-metastatic states. This near-death experience occurs in particular in the context of certain treatments aimed at depriving cancer cells of energy or oxygen. The team observed that these cells, which should have died, reprogram themselves and then present a high metastatic risk. These cells are called PAME for “post-apoptotic pro-metastatic cells.”
A storm of cytokines
To reach these conclusions, the UNIGE team used tumour samples taken from two colon cancer patients. Tumour cells from these samples were then transplanted into mice, where they grew and formed new tumours. These cells were subjected to an imminent death experience causing endoplasmic reticulum stress similar to that caused by certain chemotherapeutic drugs. This allowed the development of PAME cells.
The scientists also discovered that PAMEs trigger a storm of cytokines — proteins and other factors that ensure cell-to-cell communication — inducing adjacent cells to become PIMs, for PAME-induced migratory cells. These PIMs then associate with PAMEs and help them migrate to form metastases.
The present results open up promising new prospects for therapeutic management, including the prevention of the development of pro-metastatic fields generated by certain treatments. “Currently, one of the main criteria when defining a treatment is tumor shrinkage. Thanks to our study, PAME cells now appear as potential therapeutic and metastasis prevention targets to be taken into account,” concludes Professor Ruiz i Altaba.
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Materials provided by Université de Genève. Note: Content may be edited for style and length.

New research shows that Mindfulness-Based Cognitive Therapy (MBCT) can help promote self-kindness in people with a history of depression, thereby putting their bodies in a state of safety and relaxation.
The research, led by the University of Exeter with collaboration from the universities of Oxford and Magdeburg, indicates that MBCT may help break the cycle of highly critical thoughts and feelings of worthlessness, which often lead people with depression to relapse.
Participants treated with MBCT showed a pattern of being kind to themselves, along with body responses of reduced threat response, a state of safety and relaxation that is important for regeneration and healing.
The authors believe the study helps to better understand how MBCT prevents relapse.
MBCT is an effective group-based psychological treatment that helps people change the way they think and feel about their experiences and learn skills that reduce the likelihood of further episodes of depression.
Previous research has shown that individuals with recurrent depression benefit particularly from MBCT when they learn to become more compassionate towards themselves.

A real-time electronic decision support system helped clinicians at community hospitals provide best practice care for emergency department patients with pneumonia, resulting in decreased intensive care unit admission, more appropriate antibiotic use, and 38% lower overall mortality according to a new study by researchers at Intermountain Healthcare in Salt Lake City.
Results of the study are published online today in the American Journal of Respiratory and Critical Care Medicine.
“Treating pneumonia in emergency departments is challenging, especially in community hospitals that don’t see severe pneumonia as often as urban academic medical centers,” said Nathan Dean, MD, section chief of pulmonary and critical care medicine at Intermountain Medical Center and principal investigator of this study.
Pneumonia was the leading cause of death from infectious diseases in the United States, even before the COVID-19 pandemic, and continues to be a leading cause of death.
In the study, researchers at Intermountain Healthcare deployed the health system’s electronic, open loop, clinical decision support (ePNa) system to 16 of its community hospitals between December 2017 to June 2019.
In that time, those hospitals had 6,848 pneumonia cases, and ePNa was used by a bedside clinician in 67% of eligible patients.

Hair is an important feature of primate — including human — diversity and evolution, serving functions tied to thermoregulation, protection, camouflage and signaling. However, the evolution of wild primate hair remained relatively understudied until recently.
Researchers in the Primate Genomics Lab at the George Washington University examined what factors drive hair variation in a wild population of lemurs known as Indriidae. Specifically, the researchers aimed to assess the impacts of climate, body size and color vision on hair evolution. They found: Sifaka lemurs, which are native to Madagascar, have denser hair in dry, open environments. The researchers believe that, like early humans, the lemurs’ hair helps protect against the strong rays of the sun. Lemurs in colder regions are more likely to have dark hair. This is the first evidence in mammals for a classic pattern in nature called Bogert’s Rule, which states that dark colors could aid with thermoregulation as they help absorb heat from the sun’s rays. Red hair in lemurs is associated with enhanced color vision. According to the researchers, populations that can see a larger range of colors are more likely to have patches of red hair. Multiple evolutionary pressures may act on one trait and the strength of their influence may vary between species.”Human hair evolution remains a mystery, largely because hair does not fossilize,” Elizabeth Tapanes, lead author on the paper and a postdoctoral scholar at the University of San Diego, California, said. (Tapanes conducted the study while a doctoral student at GW.) “The lemurs we studied exhibit an upright posture like humans and live in a variety of ecosystems like early humans, so our results provide a unique window into human hair evolution.”
Brenda Bradley, an associate professor of anthropology who directs GW’s Primate Genomics Lab and is a co-author on the study, explained our understanding of hair evolution and diversity in other primates helps us fill in the gaps of our own human evolutionary story.
“Most people are intrigued by the diversity of hair on their own bodies, and the variety of hair types among people around the world,” Bradley said. “Understanding hair patterns in non-human primates, such as these lemurs, may provide a comparative context for understanding how variation arose in human hair.”
The researchers note future work should focus on samples across smaller geographic or phylogenetic (family-level, genus-level) scales and from diverse non-human and human populations.
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Women who received treatment for overactive bladder (OAB) using asynchronous telehealth visits had significant improvement in their symptoms and high satisfaction with their care, concludes an exploratory pilot study published in Menopause.
Overactive bladder is a common disorder that affects one in five women. This condition dramatically affects the quality of life of women affected by it, but treatment adherence is notoriously low. “Successful treatment of overactive bladder often requires both medication and altering behavior, such as reducing the amount of liquids consumed and cutting back on beverages containing caffeine, a bladder irritant,” says first author Marcus Ortega, MD, a female pelvic medicine and reconstructive surgeon at Massachusetts General Hospital (MGH). “Patients often discontinue medications because of side effects, and the behavioral changes aren’t easy to make without positive reinforcement and objective proof that they are effective. We wanted to test whether we could enhance treatment by keeping patients engaged in care and expediting therapy options.”
The 23 women enrolled in the pilot study had been newly diagnosed with OAB during an in-person outpatient visit at MGH. Instead of scheduling a traditional clinic follow-up visit for OAB at three months, however, the women received their first asynchronous visit approximately one month from their initial in-office visit. The telehealth visit consisted of an electronic questionnaire from a clinician asking patients about their symptoms and treatment progress. Based on the patient’s answers, the clinician responded with specific recommendations. “For example, the clinician might recommend switching to a different medication because of side effects or lack of efficacy, or reinforce certain behaviors to improve symptoms,” Ortega explains. “The patient’s answers on the validated medical questionnaires also allow us to objectively compare over time whether symptoms are improving, since it can be difficult for patients to keep track of subjective symptoms month after month.”
The study participants completed a total of 50 e-visits over a mean 135 days, with most women completing two telehealth visits. All study participants had a statistically significant improvement in urinary symptoms and a decrease in the number of incontinence episodes between their first asynchronous visit and the last one. The women reduced their fluid intake, including caffeinated and carbonated beverages, and more than 30% switched medications or had the dosage adjusted. Participants were very satisfied with the experience, rating the asynchronous visits an 8.8 on a 10-point satisfaction scale.
Despite the recent advances in overactive bladder therapies, nearly 50% of patients are frustrated with treatment results. The investigators attribute the participants’ improvement in urinary symptoms in this study to more frequent engagement with their clinicians, which ultimately led to the patients’ better compliance in behavioral changes and medication use. Asynchronous visits may also accelerate the time for patients to receive advanced therapies, such as Botox injections, tibial nerve stimulation, or sacral neuromodulation. Often, insurance companies require at least two medication trials before approving advanced treatment options, and asynchronous visits allow clinicians to more quickly optimize treatment and try different medications, as opposed to waiting 90 days for the patient to return for a follow-up office visit.
The investigators plan to conduct a randomized clinical trial to test whether asynchronous visits improve outcomes in OAB compared with regular office-based care. “If we can confirm the efficacy of this delivery model in a randomized trial, we hope this platform will become more widely available for other medical conditions,” says Ortega. In addition to keeping patients engaged in follow-up care, asynchronous visits offer many other advantages, such as not requiring a camera, reduction in unnecessary medical visits, and the convenience of receiving care at a distance, especially in rural areas where few specialists practice.
Ortega is an instructor at Harvard Medical School (HMS) and a Massachusetts General Physicians Organization Management Fellow. Other key authors are Marcela del Carmen, MD, MPH, president of the Massachusetts General Physicians Organization and professor of Obstetrics, Gynecology, and Reproductive Biology at HMS; May Wakamatsu, MD, director of Female Pelvic Medicine and Reconstructive Surgery and vice chair of Gynecology at MGH; and Jason Wasfy, MD, MPhil, medical director of the Massachusetts General Physicians Organization, director of Quality and Analytics at the MGH Heart Center, and associate professor of Medicine at HMS.
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Researchers at the University of California, San Francisco, have successfully leveraged an FDA-approved drug to halt growth of tumors driven by mutations in the RAS gene, which are famously difficult to treat and account for about one in four cancer deaths.
Taking advantage of what they discovered to be the cancer cells’ appetite for a reactive form of iron, the researchers tweaked an anticancer drug to operate only in these iron-rich cells, leaving other cells to function normally. The achievement, described in the March 9, 2022 issue of the Journal of Experimental Medicine could open doors to more tolerable chemotherapy for many cancers in which current treatments can be as challenging as the disease.
“RAS mutations, by themselves, cause more misery than all other cancers combined, and take so many lives worldwide,” said Eric Collisson, MD, a senior author of the study and member of the UCSF Helen Diller Family Comprehensive Cancer Center. “This study brings us much closer to addressing the unmet need for better treatment of these cancers.”
A Cancer Drug with an Iron Sensor
To do so, Collisson and lead author Honglin Jiang, MD, both oncologists at UCSF, teamed up with Adam Renslo, PhD, a pharmaceutical chemist also at UCSF and co-senior author, to focus on RAS-mutated pancreatic and gastrointestinal cancers. The RAS gene plays a role in tamping down pathways in the cell that drive it to grow and divide. Mutations in the gene usually mean that these growth forces are going unchecked, leading to cancer.
Current treatments, such as a drug called cobimetinib, do a good job of blocking this excessive growth activity set in motion by the mutation, but they do so in many other, non-cancerous tissues as well, leading to serious side effects that many patients find intolerable.

SharecloseShare pageCopy linkAbout sharingImage source, ReutersAustria has decided to suspend its mandate for compulsory Covid-19 vaccinations for over-18s, days before it was due to start enforcing it.It was the first EU country to adopt the measure. The government now says it considers it disproportionate to the threat posed by the Omicron variant. Health Minister Johannes Rauch said the decision would be reviewed again in three months, and could be reintroduced if a new variant made it necessary.It comes as nearly 48,000 new infections were announced in Austria, more than at any time since the pandemic began.More than 2,500 people are being treated in normal hospital wards and 182 in intensive care, but the Omicron variant has not led to a surge in admissions as feared.Austria first introduced the law on 16 February but promised not to enforce it for a month.Austria’s vaccine mandate kicks in amid resistanceHow new drugs are finally taming the virusThe plan was then to start fining those who were unable to produce proof of vaccination when asked.But Constitutional Affairs Minister Karoline Edtstadler said a commission of health and legal experts had recommended a suspension.”There are many convincing arguments at the moment that this infringement of fundamental rights is not justified,” she said.The mandate was introduced partly because of Austria’s relatively low vaccination rate – 70% of Austria’s 8.9 million people are double-vaccinated and 54% have also had a booster.Like other European countries, Austria has been removing restrictions for vaccinated people.Remaining restrictions, except for rules on masks, are expected to be lifted on 20 March. More on this storyAustria and Germany decide to ease Covid rulesAustria’s vaccine mandate kicks in amid resistanceHow new drugs are finally taming the virus