SARS-CoV-2 study on mechanisms involved in alveolar infection

Universitätsmedizin Berlin, a team of Berlin-based researchers have simulated SARS-CoV-2 infection in human lungs, thereby generating key insights into the mechanisms involved. Using cultured lung tissue samples, the researchers showed that the virus responsible for COVID-19 has only limited capacity for directly infecting cells within human alveoli. The majority of viruses which reach the lungs are ingested by macrophages (cells of the innate immune system). Ingestion activates a targeted anti-viral immune response within these immune cells. Results from this study have been published in the European Respiratory Journal.
Researchers across the globe continue their endeavors to improve our understanding of the mechanisms underlying COVID-19 infection and the pneumonia and lung damage occasionally associated with it. As part of these endeavors, researchers from Charité, the Berlin Institute of Health at Charité (BIH), the Max Delbrück Center for Molecular Medicine (MDC), the Robert Koch Institute, and Freie Universität Berlin have analyzed the propagation of, and immune activation by, SARS-CoV-2 viruses inside human lungs. Specifically, the researchers focused on cells within the alveoli and alveolar macrophages. The latter are phagocytic cells of the innate immune system which clean the lungs by ingesting and eliminating foreign particles, including infective pathogens such as viruses and bacteria.
Led by Prof. Dr. Andreas Hocke of Charité’s Department of Infectious Diseases and Respiratory Medicine, the team of researchers found that SARS-CoV-2 infects very few of the epithelial cells lining the alveolar surface, meaning that it causes very little direct tissue damage. In this respect, the virus differs significantly from both MERS-CoV and influenza viruses. Using comprehensive spectral microscopy-based analyses, the researchers were also able to show that only very few alveolar epithelial cells possess ACE2 receptors, which are required by SARS-CoV-2 to gain entry into host cells.
“Using human lungs and lung organoids — models of human alveoli developed using stem cells harvested from human lung tissue — we were able to show that SARS-CoV-2 is directly dependent on its receptor. By doing so, we were able to exclude other, alternative receptors,” explains the study’s first author, Dr. Katja Hönzke of Charité’s Department of Infectious Diseases and Respiratory Medicine. When large quantities of SARS-CoV-2 reach the alveoli from the upper respiratory tract, these do not propagate widely within the lungs’ epithelial cells, as is often the case in other severe viral infections. Instead, they are subject to ingestion by macrophages. “Using detailed bioinformatics analyses and COVID-19 autopsy samples, we observed that the macrophages change after ingesting coronaviruses,” says co-first author Dr. Benedikt Obermayer-Wasserscheid of the BIH. These changes in turn trigger a range of reactions which are associated with pneumonia. The macrophages release inflammatory messengers and can occasionally set off severe inflammatory cascades. The researchers also observed that the virus does not replicate inside these immune cells.
Explaining the researchers’ findings, Prof. Hocke says: “Our study suggests that severe lung injury in COVID-19 is more likely to be due to macrophage-induced immune activation than direct, virus-induced damage to the alveoli. As such, it makes a major contribution to our understanding of disease progress during the early phase of potential COVID-19 pneumonia and shows why, in contrast to MERS coronaviruses, most cases of SARS-CoV-2 infection show relatively moderate disease severity.” It is therefore safe to assume that, in most cases of SARS-CoV-2 infection, local immune mechanisms within human lung tissues are effective at removing the virus and limiting inflammatory response. Where this fails to happen — something which may be affected by individual risk factors — the infection may, in rare cases, prove severe and even fatal. Prof. Hocke continues: “The lung models we used provide an excellent example of how human cell-based alternatives to animal models are particularly useful in zoonotic diseases research. We were able to do this thanks to our close collaboration with Charité 3R, a facility dedicated to developing alternatives to animal-based research.”
Subsequent research will focus on patient-derived organoid models, which will be used for a more detailed study of how general risk factors such as age, gender, concomitant disease and different medicines affect the activation of the immune response. This knowledge may then enable the identification of possible treatment approaches targeting the immune system.
About this study
This research received funding from the German Research Foundation (DFG) as part of the Collaborative Research Center SFB-TR84 ‘Innate Immunity of the Lung’. Additional funding was provided by the Einstein Foundation Berlin (Einstein Center 3R), as well as the ‘Organ-specific Stratification in COVID-19’ (Organo-Strat) research collaboration, which is funded by the Federal Ministry of Education and Research (BMBF). This research collaboration was conducted under the auspices of the NUM, an academic research network initiated and coordinated by Charité. The NUM brings together the combined strength of Germany’s 36 university hospitals.
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Materials provided by Charité – Universitätsmedizin Berlin. Note: Content may be edited for style and length.

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Exercise-induced central fatigue — low oxygen supply clouds judgment

When physically demanding activities are performed at high altitude or in other low-oxygen environments, excellent coordination, judgment, and decision-making are important. In some cases, such as when mountaineering, these capabilities may be the difference between life and death.
What is executive function and why is it important? Executive functions control and coordinate other brain functions, like memory, emotions, and movement control, to enable more complex behaviors — for example, learning, planning, judgment, and decision-making.
In a study published this month in Scientific Reports, researchers at the University of Tsukuba showed that reductions in neural activity in brain regions responsible for executive control-related cognitive functions and cognitive performance during exercise in low-oxygen conditions could be prevented by maintaining oxygen saturation.
Demonstrating causality — that the decreases in neural activity and performance are caused by low oxygen availability to brain tissue — is not straightforward because of the complexity exhibited by the brain and all its functions. Yet the University of Tsukuba research team have done just that. “We compared the effects of hypoxic conditions in which blood oxygen levels is reduced with those in which blood oxygen levels remains stable during exercise,” says senior author Professor Hideaki Soya. “By doing this, we isolated low oxygen saturation as a factor for decreased neural activity and decreased performance.”
Neural activity in the prefrontal cortex was measured with functional near-infrared spectroscopy to show change in oxygenated hemoglobin (i.e., oxygen usage from regional blood supply). Cognitive performance was assessed using Stroop interference, which is the difference in completion time (or number of errors) between neutral and incongruent trials. In incongruent trials, the color of the text must be identified when, for example, the word red is written in green. In neutral trials, only the color of a swatch must be identified.
“When blood oxygen levels remained stable during exercise, the Stroop effect was not as pronounced,” says senior author Dr. Genta Ochi. “In the brain region of interest — the left dorsolateral prefrontal cortex — there was less of a decrease in activation from the neutral to the incongruent trial.”
The study suggests that oxygen supply is important for maintaining cognitive function during exercise in low-oxygen environments. Furthermore, regions of the brain with newer (from an evolutionary point of view), less critical functions may be lower priority than those responsible for functions that keep us alive. Thus, the effects of cognitive fatigue must be taken into account when physical activities that require judgment and critical thinking are performed in low-oxygen environments.
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Materials provided by University of Tsukuba. Note: Content may be edited for style and length.

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Skin's protective chains uncovered

The skin’s top layer contains a diverse set of hundreds of lipid molecules called ceramides with varying chain lengths that play a vital role in its barrier function.
Ceramides are a type of lipid that are found in abundance in the top layer of the skin, called the stratum corneum. They play a crucial role in the skin’s barrier function, preventing entrance of pathogens and allergens and the loss of water and electrolytes. Mutations in the genes involved in the production of ceramides lead to a wide range of skin diseases.
A new analytical approach has revealed the full range of different ceramides found in the top layer of human skin. The results were published by Hokkaido University scientists in the Journal of Lipid Research and could improve understanding of skin diseases like psoriasis and dermatitis.
Scientists have struggled to get a full picture of the types of ceramides present in the stratum corneum due to difficulties in separating them from each other and then specifically identifying each one. The technological approaches that have so far been used to do this have not been sensitive enough.
Professor Akio Kihara and fellow biochemists at Hokkaido University in Japan developed an approach to address this. They used a method called liquid chromatography with tandem mass spectrometry using the multiple reaction monitoring mode. This approach separates the various ceramides in the skin and then selectively quantifies them by converting molecules into ions that are manipulated in electric and magnetic fields to sort them according to their mass-to-charge ratios.
By doing so, the team identified 1,327 different unbound ceramides and another 254 that are bound to proteins. They were also able to discover certain details of the ceramides, such as the lengths of their basic structural unit, called the long-chain base and the types of fatty acids they are conjugated to. They found, for example, that the long-chain bases ranged in length from 16 to 26 carbon atoms and that the 18-carbon-atom length was the most abundant.
Further analyses revealed that an enzyme called serine palmitoyltransferase was important for the diversity in ceramide long-chain base length in human stratum corneum.
“Total ceramide chain length is reduced in people with atopic dermatitis,” says Kihara. “We think that the presence of the longer long-chain bases in ceramides is required for normal skin barrier function. In the future, comprehensive measurements of ceramides in people with skin disease could reveal the relationship between changes in ceramide composition and the pathology of each disease.”
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Study paves the way towards a more precise use of CRISPR

Human imagination is the only limit when it comes to the potential of genetic engineering — especially after the breakthrough of CRISPR technology.
A new Danish research project can help refine the method and is a step towards a more precise and effective use of ‘genetic scissors’.
“Our study shows that, by better understanding the CRISPR/Cas9 protein and its gRNA component, we can more accurately hit and cut the DNA and thereby optimise the effectiveness of gene modification,” says Yonglun Luo, associate professor at the Department of Biomedicine, Aarhus University.
Revolutionary technology
Ten years ago, researchers identified a protein in bacteria that can cut DNA, and which uses a so-called guide RNA to recognise where DNA needs to be cut. The CRISPR method has been hailed as a revolution within gene technology ever since.
CRISPR makes it possible to remove or insert the exact genes you want in any living organism — from bacteria to plants to humans.

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These TikTok Creators Are Fighting Health Myths

Meet the medical experts fighting bogus science, one “stitch” at a time.“I’m willing to bet you know at least one girl that’s using steroids every single day,” starts a young man in a TikTok video.He stares into the camera, continuing his big, yet notably false, reveal: “One in three girls these days is taking the birth control pill, and believe it or not, the birth control pill is actually an analog of the bodybuilding steroid nandrolone.”Another face swiftly crowds the screen. Dressed in a white lab coat, the debunker Mustafa Dhahir, a practicing pharmacist and medical student based in Australia, interrupts the video with his own commentary: “One of the most annoying things when it comes to busting misinformation is that the people who spread the misinformation use hints of truth to spread their lies.”Mr. Dhahir explains what a steroid is and then goes point by point to illustrate why the original video — which claims oral contraception causes a medley of symptoms, including changes in sexual attraction — is inaccurate. “This guy is simply using scare tactics,” Mr. Dhahir tells the viewer, noting that there are many birth control options with varying sets of side effects.

@pharmustafa #myth #fyp #misinformation #pharmacist #doctor #pharmacy #medicine #health #contraception ♬ original sound – Mustafa D Mr. Dhahir is part of a growing cohort of scientists, physicians, health care professionals and academics who debunk health misinformation on TikTok by “stitching” videos, which involves clipping existing videos into new ones and then offering one’s own input. While social media platforms including TikTok have developed systems to flag vaccine misinformation, an ocean of other dubious health claims often go unscrutinized — except when individual users like him, who have actual medical knowledge, push back.“Misinformation impacts medical decisions and health,” said Mr. Dhahir, who began responding to false claims on TikTok at the start of the pandemic and has since amassed 9.5 million likes on his videos. He has debunked claims that contraception makes women infertile, that only “natural” medicine can be trusted and that Tylenol is linked to autism.The work is often draining. Unqualified influencers posting misinformation far outnumber the experts debunking it, who are often harassed by other users for their efforts. “For every large creator who is genuinely evidence-based, you’ve got 50 or 60 big creators who spread misinformation,” said Dr. Idrees Mughal, a Britain-based physician with an additional masters in nutritional research, whose account, @dr_idz, has 1.3 millions followers. He debunks fad diets, unsupported claims that food ingredients are “cancer-causing” and the myth that certain vegetables contain harmful “toxic” chemicals. Misinformation is so ubiquitous that Dr. Mughal says he is tagged in 100 to 200 videos a day from users requesting that he debunk claims. “People are looking for genuine science-based, evidence-based creators,” he said.Fertile ground for pseudoscienceMisinformation is widespread on all of the major social media platforms, but TikTok’s audio capabilities can give false claims particular longevity. Bits of misinformation clipped and saved as what TikTok calls sounds “operate like viral chain messages,” according to a 2021 blog post from the Institute for Strategic Dialogue, a London-based center that researches disinformation and extremism online. Even if a video is taken down, the original audio often survives in the work of users who have already borrowed it for their own content.TikTok has enacted policies to flag such content, including adding informational banners to Covid-19 vaccine content, but one I.S.D. study of more than 6,000 videos related to the vaccines found that 58 percent lacked banners. When it comes to combating health misinformation in general, all social media platforms face a daunting task, given the sheer volume of inaccurate posts. In a statement, TikTok wrote, “We work diligently to take action on content and accounts that spread misinformation, while also promoting authoritative content about vaccines through our Covid-19 information hub.”When asked if TikTok was addressing general health misinformation, the company replied that ​​it both removes violations of the platform’s policies and works “with credible voices to elevate authoritative content on topics related to public health.”Abbie Richards, a misinformation and disinformation researcher and research fellow with the Accelerationism Research Consortium, an organization aimed at understanding and addressing the threat of extremism, said TikTok’s video format was also advantageous in spreading conspiracies. Creators speak directly into the camera as if they’re on a video call with the viewer. “It feels more authentic than disembodied text,” Ms. Richards said, which can make it seem more credible.Timothy Caulfield, the Canada research chair in health law and policy at the University of Alberta, studies misinformation on social media and said that research had shown that a powerful personal anecdote, testimonial or narrative could overwhelm people’s ability to think scientifically. Coupled with creative visuals, “those elements have made it a very consumable and powerful way to spread misinformation,” he said.Pseudoscience creators have built on the inherent velocity of social media platforms with tactics of their own. Many use shock and fear to make bogus health claims seem more urgent and credible. One video that Dr. Mughal debunked claimed that many people unknowingly have parasites living in their gut that cause chronic illnesses and that the solution is buying “parasitic cleansing kits.”Then there is “science-washing,” a term debunkers use to describe how pseudoscience creators deploy scientific-sounding language to weigh in on health issues, cherry-pick studies to support false claims or cite studies that seem relevant but are not.In TikTok’s beauty circles, Michelle Wong, a cosmetic chemist who runs Lab Muffin Beauty Science, a blog and social media accounts that explain the science behind skin care and cosmetic products, has made a new career out of fighting misinformation. She often encounters creators who take ingredients out of context, sometimes conflating topical use with ingestion — an important distinction, as consumers don’t drink their moisturizers. Ms. Wong also sees pseudoscience creators who back up false, fear-mongering claims about sunscreen with white papers the creators either don’t have full access to or don’t understand. “That in itself is quite convincing, because very few people are actually going to look up every single paper listed,” she said.The lack of science literacy online was partly what inspired Katrine Wallace, an epidemiologist and a professor at the University of Illinois at Chicago, to start debunking inaccurate content on TikTok. At the start of the pandemic, she noticed that users were debating whether Covid was even real, and she has since debunked videos stating that Covid vaccines cause death within six months, for example, and that microscopic worms or parasites are found in surgical face masks. That topic recirculates every six months, she said in an interview, adding, “People are obsessed.”

@epidemiologistkat Answer to @natmatmom no there are not worms or parasites in masks #conspiracytherory #worms #parasites #masks #epidemiology #prevention #publichealth ♬ original sound – Dr Kat, Epidemiologist Viewers are drawn to surprising or extreme statements, and highly engaged content is promoted by the app’s algorithm, which is why debunkers often find themselves responding to provocative assertions. For the same reasons, myth-busting response videos like Dr. Dhahir’s on oral contraception often get more views than simple explainers. “People like drama,” Dr.. Wallace said.In refuting claims, debunkers try to engage respectfully with other creators. Dr. Mughal said he refrained from insulting or attacking creators who disseminated misinformation and instead focused on addressing the health claims. Dr.. Wallace takes a different approach. She said she would first reach out privately to the original poster to explain why the video is problematic and urge them to take it down or publicly address the misinformation. “And if they block me or delete my comments,” she said, “then I’m like, ‘OK, it’s on.’”On the brink of burnout?The business of debunking is time-consuming. Scripting, filming and editing, not to mention managing comments — which sometimes also breed misinformation when users share counterarguments — can take hours each day. To attract an audience, each video must accurately convey the science but must also be entertaining and approach the topic with nuance and sensitivity, all while grabbing the viewer’s attention within 15 seconds.When Ms. Wong was a full-time science educator, she found herself working an extra 30 hours a week creating content for social media and her blog. “It was just destroying my personal life,” she recalled, adding that her relationship with her partner had ended partly because she was spending so much time on content creation.It doesn’t help that debunking often won’t pay the bills, as many myth busters refrain from accepting sponsorships to prevent a conflict of interest. Ms. Wong accepts sponsorships, but like others who work with brands, she is selective, avoiding clients with deceptive marketing practices or cure-all claims.“It is possible to work with brands and still remain fact-based and science-based,” she said, but she acknowledged that “part of it is necessity — because debunking was taking up so many of my hours.”Ms. Wong quit her job in 2019 to devote herself full-time to Lab Muffin Beauty Science, but she still sometimes works up to 70 hours per week. “Science just takes so much longer than misinformation, because you have to do the research properly,” she said.Once a debunker has an audience, the work of maintaining and building an account can also lead to burnout. Like most influencers, they put pressure on themselves to excel. As Dr. Austin Chiang, a gastroenterologist with over a half-million TikTok followers, explained, they often blame themselves if their content underperforms. “We think, is it because my messaging isn’t good?” he said. “Is it because the quality of the video isn’t good?”Dr.. Wallace said the most exhausting element, though, was the harassment. Commenters repeatedly insult her, and when she posts in favor of vaccination, they accuse her of being a “shill for Big Pharma.” “I block accounts every day,” Dr.. Wallace said. She also received threatening and sexually violent messages through her university email account — a situation that she said had required the university police to become involved early this year.For health care professionals, harassment can also lead to professional consequences, or the fear of them. “Many people’s institutions don’t want them to be attracting tons of negative attention,” said Renée DiResta, a misinformation expert and the technical research manager at the Stanford Internet Observatory, which studies internet propaganda. Doctors are encouraged to treat patients. Scientists are encouraged to conduct research and submit their findings for peer review. To create content on TikTok? Less so.Mr. Dhahir considered quitting TikTok after users found the address of his pharmacy and spread rumors about his professional and personal lives. He also had to meet with the dean of medicine at the University of Sydney and explain why the university had received complaints. Mr. Dhahir said he felt supported by his university but worried that that could change quickly. “One wrong move, and then my work can fire me or the university can kick me out,” he said. “I have to make sure I don’t screw up.”Dr. Mughal said he had heard from fellow doctors who balked at making educational content on social media lest complainers “get them into trouble.” “There’s not a lot of protection for health care professionals that make content for the public,” he said. Creators said they feared losing their licenses or memberships in professional associations. Doctors who work in private practice worry that critics will flood Yelp with negative reviews.Ms. DiResta stressed the importance of health experts’ engaging with the public on social media, but until there is stronger support from institutions, she hestitates to recommend that they do so: “They have to know what’s going to happen to them when they do it. That’s the problem,” she said.Many solutions, though not always agreementWith debunker burnout on the horizon and a never-ending flow of pseudoscience, researchers said they needed more data to determine which strategies worked best for countering misinformation. Some say that TikTok should promote evidence-based health content on the “For You” page, the platform’s personalized feed of recommended content, so it doesn’t get lost among similar-sounding videos pushing misinformation.Not everyone is eager to see a platform artificially elevating health experts, though. Dr. Karan Raj, a surgeon for Britain’s National Health Service who has garnered 4.8 million followers on TikTok by discrediting claims like the warning that holding in gas causes appendicitis or that desiccant tablets found in pregnancy tests are a form of Plan B, argued that top-down promotion could erode audience trust.“People should want to watch content because they enjoy the content,” Dr. Raj said, insisting that videos needed to gain popularity of their own accord. “If I get on the ‘For You’ page, it’s because people like my content.”Ms. Richards pointed out that ensuring that a video from, say, the W.H.O. gets millions of views doesn’t ensure that the information will affect users, noting that impact is gauged through a mixed methodology that analyzes several factors, including engagement, watch time and shares.Some researchers recommend that TikTok work with health organizations to identify experts who can explain complex health issues in layperson’s terms, as the platform did with Covid-19 efforts. Ciaran O’Connor, an analyst who studies disinformation at the Institute for Strategic Dialogue, suggested that TikTok offer experts verified badges as a stamp of authority.But misinformation experts and creators alike argued that social media platforms are not solely responsible for amplifying accurate information. They want institutions and health departments to further invest in influencers. They also want stronger initiatives to support creators, like financial compensation, mental health resources or help handling harassment. “For all of the experts who are on there trying to put out high-quality information, if we want that to be sustainable for them, we need to be building infrastructure that doesn’t rely on the platforms,” Ms. Richards said. Right now, she said, “It’s viewed as a hobby, almost like charity work.”Despite the hurdles, debunkers do see their efforts paying off. Followers have told Dr. Wallace that they got vaccinated after watching her videos. Mr. Chiang heard from viewers who got screened for medical conditions they might have otherwise ignored. And Mr. Dhahir’s fans sometimes reach out to say thank you.“They’ll say, ‘I appreciate everything,’ or, ‘You’ve inspired me,’” Mr. Dhahir said, adding, “Then I’ll be like: ‘You know what? This is actually worth it.’”Rina Raphael is the author of the forthcoming book “The Gospel of Wellness.”

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Measuring levels of proteins in eye fluid may accurately predict need for lifelong macular degeneration therapy

In a study of eye fluid from 38 patients, Johns Hopkins Medicine researchers say they have found that levels of a specific protein appears to help accurately predict whether people with the wet form of age-related macular degeneration may need lifelong, frequent eye injections to preserve vision or if they can be safely weaned off the treatments.
The researchers say the protein could also be targeted by new therapies to halt vision loss among patients with the disorder, caused by abnormal growth of blood vessels that leak fluid or bleed into the portion of the retina needed for central vision
The researchers’ findings were published online June 2 in the Journal of Clinical Investigation Insight.
Overall, age-related macular degeneration is the most common cause of vision loss among people age 50 and older, affecting an estimated 7.3 million individuals in the United States.
Standard treatment of wet age-related macular degeneration requires monthly or twice-monthly eye injections of so-called anti-VEGF drugs that slow or stop the growth of leaky blood vessels and, in most cases, stave off further vision loss.
Because the injections are inconvenient, costly, uncomfortable, and carry risk of infection, retinal detachment and other side effects,
Sodhi’s research team has long been studying ways to identify subgroups of patients who can safely reduce — or even cease — eye injection therapies without further vision loss.

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Off-shelf glucose monitors prove accurate for dialysis patients

In what is believed to be the first study of its kind, new UVA Health research reveals that a factory-calibrated continuous glucose monitor (CGM) may be sufficiently accurate for use by people on dialysis, a group often plagued by dangerous swings in blood-sugar levels.
The findings suggest that factory-calibrated blood glucose monitors could offer an important diabetes-management tool for patients on dialysis and those suffering end-stage renal disease [ESRD], the researchers conclude.
“Patients with end-stage renal disease are often excluded from clinical research trials, as they are medically complex. Therefore, these CGM devices — often considered ‘game changers’ for patients with diabetes to monitor their sugars — are not yet FDA approved for patients with ESRD on dialysis,” said researcher Meaghan M. Stumpf, MD, an expert on diabetes and diabetes-management technology at UVA Health. “However, ESRD patients and their physicians may still benefit from their use. Our research team conducted this pilot study so that we could begin to understand the accuracy of these devices for patients with ESRD on hemodialysis. This study is not large enough to lead to FDA approval, but it is important to take the first step.”
Continuous glucose monitors are becoming widely used by patients with diabetes. These devices allow patients to track their blood-sugar (glucose) levels automatically, helping them prevent their blood-sugar levels from getting dangerously high or low.
Managing blood-sugar levels is a particular challenge for patients on dialysis, which is a procedure to filter blood for patients whose kidneys can no longer do so adequately. Patients on dialysis often suffer from “hypoglycemia,” or low blood sugar, which is potentially deadly. That means that these patients need highly reliable, accurate ways to track their blood sugar. Until now, physicians and researchers did not have accuracy data for factory-calibrated continuous glucose monitors, so it was unclear if these devices would be up to the job.
To determine this, Stumpf and her colleagues enlisted 20 volunteers receiving hemodialysis at UVA to test such a device, the Dexcom G6-Pro. Most of the participants were male, African-American, and on insulin, with an average age of 61. The participants were asked to wear the CGM for 10 days and to take four to seven fingerstick blood-sugar readings per day with a home glucometer. Venous blood samples were also collected during their hemodialysis sessions. The researchers compared the CGM glucose results with the blood-sugar results collected by the patients and during the patients’ thrice-weekly dialysis sessions.
The researchers determined that the continuous glucose monitor, overall, showed “clinical reliability,” meaning that they were sufficiently accurate for estimating blood-sugar levels. Almost 99% of the readings were accurate enough to be used without confirmatory fingerstick blood sugar readings.
When the devices erred, they tended to overestimate, rather than underestimate, blood-sugar levels, prompting the researchers to note that additional research is warranted, especially considering that people on dialysis tend to be at elevated risk for low blood sugar.
“Although we certainly need larger studies, I am encouraged that these factory- calibrated continuous glucose monitors may be reasonably accurate for patients on hemodialysis therapy,” Stumpf said. “CGM use for these patients could lead to improved glucose control, improved safety from life-threatening hypoglycemia and, very importantly, improved quality of life.”
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Materials provided by University of Virginia Health System. Note: Content may be edited for style and length.

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Combining genetics and brain MRI can aid in predicting chances of Alzheimer's disease

Simon Fraser University researchers are studying how a combination of genetics and brain MRIs may be used to predict the chances of developing Alzheimer’s disease in the future.
In a newly published study, researchers from SFU’s Functional and Anatomical Imaging & Shape Analysis Lab (FAISAL) identified distinct properties of brain MRIs and genetics that impact the prediction of Dementia of Alzheimer’s Type, or DAT, for patients at various stages of the disease, then developed a biomarker that can help predict future conversion to DAT.
“Our findings reveal that while genetic features have lower predictive power than MRI features, combining both modalities can improve the performance in predicting the future conversion to DAT,” says study lead author Ghazal Mirabnahrazam, a research assistant currently completing a master’s degree in engineering science at SFU.
Dementia scores based on genetic data were shown to better predict future DAT progression in currently normal patients who will develop DAT at a later time, while MRI data, which reflects anatomical changes in the brain, was shown to better predict future DAT in those with mild cognitive impairment.
“In a clinical setting, clinicians can use our model to predict a quantitative score indicating the similarity between a subject’s observed patterns based on MRI and genetic data at the time of clinical visit and DAT patterns,” says senior author Mirza Faisal Beg, a professor in SFU’s School of Engineering Science.
“This is extremely useful, specifically at the MCI (mild cognitively impaired) stage in identifying those who will progress to DAT in the future. Being able to accurately estimate the chance of future conversion to DAT using only baseline information is extremely valuable because it provides practitioners with deep insight and enough time to plan appropriate care for each patient based on their probability of developing Alzheimer’s disease.
“Furthermore, it can provide potentially critical information for drug trials and the development of preventative measures,” adds Beg. “This information can aid in the selection of the appropriate cohort of patients for clinical trials, which can lead to a more promising outcome.”
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Materials provided by Simon Fraser University. Note: Content may be edited for style and length.

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Targeting a human protein to squash SARS-CoV-2 and other viruses

More than two years into the COVID-19 pandemic, people are realizing that the “new normal” will probably involve learning to co-exist with SARS-CoV-2. Some treatments are available, but with new variants emerging, researchers are looking toward new strategies. In ACS Infectious Diseases, scientists now report that apratoxin S4, an anticancer drug candidate that targets a human protein, can interfere with the replication of many viruses, including SARS-CoV-2 and influenza A, offering a possible pan-viral therapy.
Although COVID-19 vaccines exist, some people who received the shots have still become sick with the disease, and only a fraction of the world’s population is vaccinated. That means treatments are still needed, and a few are now available that target the virus’s RNA polymerase — the enzyme it uses to make more of its own RNA inside human cells. But some of these drugs, such as remdesivir, don’t work unless given at very early stages and can require injections.
In the hunt for new ways to treat COVID-19, various teams have revisited drugs that are already known to fight other diseases, a strategy called “repurposing.” One such preclinical stage compound is apratoxin S4 (Apra S4), which is a molecule based on a natural product that has anti-cancer activity. Previous studies have shown that apratoxins can target a human protein called Sec61, which ensures that certain proteins are properly glycosylated and folded correctly. Since viruses don’t have their own machinery to do this, they hijack the process and force human cells to make functional viral proteins. Sec61 is essential for the influenza A, HIV and dengue viruses to cause infection, so Hendrik Luesch and colleagues wondered if apratoxins could be a broadly effective, pan-viral medication that could also combat SARS-CoV-2.
In tests with monkey and human cells exposed to SARS-CoV-2, the researchers found that treatment with Apra S4 reduced the number of infected cells compared with remdesivir treatment. The molecule was also effective against influenza A, Zika virus, dengue and West Nile virus infections. Further testing revealed that Apra S4 didn’t prevent SARS-CoV-2 from entering cells, but it reduced the amount of viral protein that was produced and transported in cells, especially the spike protein, and it decreased viral RNA replication. With electron microscopy, the team observed that Apra S4 also largely blocked the formation of new viruses, with many vesicles in SARS-CoV-2-exposed monkey cells having no or very few brand-new viral particles in them. The researchers say more studies are needed, but these results suggest that Apra S4 and other inhibitors of the human Sec61 protein are broadly acting antivirals that could help in the fight against future pandemics.
The authors acknowledge funding from the National Institutes of Health, the Debbie and Sylvia DeSantis Chair professorship, the Department of Defense, the Dengue Human Immunology Project Consortium, philanthropic donations, JPB Foundation, the Open Philanthropy Project and the Swiss National Science Foundation.
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Materials provided by American Chemical Society. Note: Content may be edited for style and length.

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When more is more: Identifying cognitive impairments with multiple drawing tasks

Changes in drawing traits have been reported in people with early-stage cognitive impairments, but most studies have used a single drawing task only. In a study published recently in the Journal of Alzheimer’s Disease, researchers from the University of Tsukuba and IBM Research have found that they could classify people with normal cognition, mild cognitive impairment (MCI), and Alzheimer’s disease (AD) with much greater accuracy by combining traits extracted from five different drawing tasks than by using just one or two tasks.
Around 75% of people with dementia have not been diagnosed, and this is partly because there is a lack of accurate screening tests that can be done outside of a doctor’s office or hospital. Recently, the quest for better screening techniques has become more important as new therapies are developed that can slow the progression of cognitive impairment. Researchers at the University of Tsukuba wanted to address this lack of accurate screening tests using the automatic analysis of drawing.
“Although it’s clear that motion- and pause-related drawing traits can be used to screen for cognitive impairments, most screening tests remain relatively inaccurate” says senior author of the study Professor Tetsuaki Arai. “We wondered what might happen if we were to analyze these traits while people performed a range of different drawing tasks.”
To do this, the researchers used five different drawing tests that capture different aspects of cognition and are commonly used when diagnosing AD and MCI. While these tests were being performed, 22 different drawing features — relating to pen pressure, pen posture, speed, and pauses — were automatically analyzed per test. The researchers then compared these features with scores from seven different tests of cognitive function, and used a computer-based program to see how well the drawing traits could be used to identify people with normal cognition, MCI, or AD.
“We were surprised by how well the combination of drawing traits extracted from multiple tasks worked by capturing different, complementary aspects of cognitive impairments,” explains Professor Arai. “The three-group classification accuracy of all five tests was 75.2%, which was almost 10% better than that of any of the tests by themselves.”
In addition, the majority of the drawing features that were different between the three groups had greater changes between the normal and AD subjects compared with the normal and MCI subjects — this is important because MCI is often considered an early (and less severe) form of AD.
“Although this was a relatively small study, the results are encouraging,” says Professor Arai. “Our results pave the way for better screening tests for cognitive impairments.”
With the ever-increasing numbers of therapies targeting the early stages of cognitive impairment, screening tests are becoming more important. Better screening will lead to earlier diagnoses, which will in turn improve patients’ quality of life.
This work was supported by the Japan Society for the Promotion of Science, KAKENHI (grants 19H01084 and 18K18164). The funders did not play any active role in either the scientific investigation or the reporting of the study.
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Materials provided by University of Tsukuba. Note: Content may be edited for style and length.

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