Tag: health

Poor Sleep Linked with Future Amyloid-β Build Up

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by Abby Olena

There’s evidence in people and animals that short-term sleep deprivation can change the levels of amyloid-β, a peptide that can accumulate in the aging brain and cause Alzheimer’s disease. Scientists now show long-term consequences may also result from sustained poor sleep. In a study published September 3 in Current Biology, researchers found that healthy individuals with lower-quality sleep were more likely to have amyloid-β accumulation in the brain years later. The study could not say whether poor sleep caused amyloid-β accumulation or vice versa, but the authors say that sleep could be an indicator of present and future amyloid-β levels.

“Traditionally, sleep disruptions have been accepted as a symptom of Alzheimer’s disease,” says Ksenia Kastanenka, a neuroscientist at Massachusetts General Hospital who was not involved in the work. Her group showed in 2017 that improving sleep in a mouse model of Alzheimer’s disease, in which the animals’ slow wave sleep is disrupted as it usually is in people with the disease, halted disease progression.

Collectively, the results from these studies and others raise the possibility that “sleep rhythm disruptions are not an artifact of disease progression, but actually are active contributors, if not a cause,” she says, hinting at the prospect of using these sleep measures as a biomarker for Alzheimer’s disease.

As a graduate student at the University of California, Berkeley, Joseph Winer, who is now a postdoc at Stanford University, and his colleagues were interested in whether or not sleep could predict how the brain changes over time. They collaborated with the team behind the Berkeley Aging Cohort Study, which includes a group of 32 cognitively healthy adults averaging about 75 years of age. They participated in a sleep study, then had periodic cognitive assessments and between two and five positron emission tomography (PET) scans to check for the presence of amyloid-β in their brains for an average of about four years after the sleep study.

The researchers found at their baseline PET scan, which happened within six months of their sleep study, that 20 of the 32 participants already had some amyloid-β accumulation, which was not unexpected based on their average age. They also showed that both slow wave sleep, an indicator of depth of sleep, and sleep efficiency, the amount of time sleeping compared to time in bed, were both predictive of the rate of amyloid change several years later. In other words, people with lower levels of slow wave sleep and sleep efficiency were more likely to have faster amyloid build up.

The subjects all remained cognitively healthy over the duration of the study, says Winer. “We do expect that they’re at higher risk for developing Alzheimer’s in their lifetime because of the amyloid plaque.”

The strengths of the study include the well-characterized participants with detailed sleep assessments, as well as cognitive testing and longitudinal amyloid PET imaging, says Brendan Lucey, a sleep neurologist at Washington University in St. Louis who did not participate in the work.

There are still open questions about the link between sleep and amyloid deposition over time. “Amyloid accumulation on PET increases at different rates in amyloid-negative and amyloid-positive individuals, and even within amyloid-positive individuals,” Lucey explains. “Without adjusting for participants’ starting amyloid [levels], we don’t know if some participants would have been more likely to have increased amyloid compared to others, independent of sleep.”

“It is very hard to untangle this question of baselines,” acknowledges Winer. Because the sleep measures the team identified in the study are related to amyloid levels, to actually tease apart the effect of sleep quality on amyloid deposition and vice versa, it’d be necessary to study people starting as early as their fifties, when they’re much less likely to have amyloid accumulation, he says.

This study is “a great start,” David Holtzman, a neurologist and collaborator of Lucey at Washington University in St. Louis who did not participate in the work, tells The Scientist. In addition to controlling for the amount of amyloid deposition that is present in a subject’s brain at the beginning of the study, it would be important to see if the findings bear out in larger numbers of people and what role genetic factors play.

“The most important question down the road is to test the idea in some sort of a treatment paradigm,” Holtzman adds. “You can do something to improve the quality of sleep or increase slow wave sleep, and then determine if it actually slows down the onset of Alzheimer’s disease clinically.”

J.R. Winer et al., “Sleep disturbance forecasts β-amyloid accumulation across subsequent years,” Current Biology, doi:10.1016/j.cub.2020.08.017, 2020.

https://www.the-scientist.com/news-opinion/poor-sleep-linked-with-future-amyloid-build-up-67923?utm_campaign=TS_OTC_2020&utm_medium=email&_hsmi=95303853&_hsenc=p2ANqtz–8BBfH3OsENS0A5GHEfhRVVh3ox2uWli04iEz1JAIpGp_Zeq9dMKwhb5f5X1AeB01d4d07al4rDaOWz_GzA5Ax6TXrGQ&utm_content=95303853&utm_source=hs_email

Does washing clothes kill all the germs?

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BY MARKHAM HEID

Laundry serves far nobler purposes than stamping out body odor. It also protects you from getting sick. (Brace yourself, because this is going to get gross in a hurry.)

Imagine that someone who lives in your house is ill. A single gram of his fecal matter contains millions of viruses, and exposure to just a hundred of those viruses can make you sick, says Kelly Reynolds, a germ researcher and associate professor of environmental health at the University of Arizona.

Regardless of how assiduously he wipes, the average person has about a tenth of a gram of fecal residue in his underwear, says Chuck Gerba, a professor of microbiology at Arizona. If you’re washing that sick person’s underwear with your own, chances are very good that his sickness-causing organisms are going to make their way onto your clothing.

“We’ve found that one germy item in the washer will spread to 90% of the other items,” Reynolds says. And no, it doesn’t matter how hot you set the water temperature on your machine. “When it comes to molds that cause skin or respiratory infections, or organisms that cause colds, flu and stomach flu, most of them will survive the wash cycle,” she says.

It’s the dryer—not the washing machine—that lays waste to harmful microorganisms. “High heat drying for at least 28 minutes is the most effective way to kill viruses,” Reynolds says. The “high heat” setting is key. Energy efficient, low-heat settings may not get the job done, she says.

You’re not even safe if you wash your sick housemate’s clothing separately from your own, since his germs will hang out in the washer even after the clothing is gone. Run a wash cycle with bleach or another type of disinfectant to clean it of sickness-cause organisms, Reynolds says.

The good news is that if no one in your household is sick, you can relax a bit about killing the germs in your load. “It’s when someone is ill that you really want to up your game,” Reynolds says. If your housemate catches something, have him or her wear clothing and sleep on sheets that you can wash and dry using high heat.

And yes—it’s ok to spare your expensive, line-dry only gym gear from the dryer. Your big worry there is probably foul odors, not viral pathogens. If you’re diligent about washing your hands (and wiping down the machines at the gym before you climb aboard) you shouldn’t have much to worry about, Reynolds says. Just be sure to wash your duds soon after you finish exercising. “The longer those clothes remain damp with sweat, the more mold and bacteria are going to proliferate,” she says.

If your first instinct after reading this is to double down on detergent, don’t. A washing machine’s cycles are designed to break up and wash away only so much cleaning agent, says Jolie Kerr, an author, cleaning expert and host of the podcast Ask a Clean Person. If you have a heavy hand with the pump or scoop, the excess detergent can build up on your clothing and lock in bacteria and odors, she says. (Fabric softener, too, can coat your clothing in a residue that traps smells, she adds.)

If you can’t dry your stuff on high heat—or at all—hang it up outdoors or in direct sunlight. The sun’s ultraviolet light has disinfecting properties, Reynolds says.

Finally, be mindful of transferring your clothes from the washer to the dryer. “Unless you’ve used bleach or some other disinfectant, those items are not sanitized,” Reynolds says, so be sure to wash your hands after handling them.

https://time.com/4676920/washing-machine-germs/

Thanks to Mr. C for bringing this to the It’s Interesting commmunity.

Public restroom hand dryers found to harbor Staphylococcus and fecal matter

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Automatic hand dryers in men’s and women’s public restrooms can harbor and spread bacteria, including Staphylococcus and fecal matter, according to research presented during ASM Microbe, which is being held virtually this year.

To assess the contamination of public restroom hand dryers, Craig Oberg, PhD, Brady Distinguished Professor of Microbiology at Weber State University in Ogden, Utah, and two undergraduate students collected samples using 3M Quickswabs from three different locations in each hand dryer — the top of the dryer above the air vents, in the middle beneath the air vents on the internal part of the dryer and the bottom of the dryer.

“Initially, the students were looking for contamination on exercise equipment, then they started looking at other common use equipment in gym areas and restrooms when they settled on hand dryers, especially since they have the potential to aerosolize into the surrounding area,” Oberg told Healio.

Results of the study showed that the bottom of dryers in both the men’s and women’s restrooms had the most contamination, with an average of about 300 organisms/5 cm2, followed by the middle section, which had roughly half as many organisms, averaging 140 organisms/5 cm2 and the top of the dryer, which contained 75 organisms/5 cm2. The researchers said there was no overall difference between the two brands of dryers tested in the study — Dyson Airblade and Mediclinics Dualflow Plus.

As far as finding safer ways to use the dryers, Oberg said the best option is to redesign them with internal ultraviolet light sources to prevent the buildup of microorganisms inside the dryer.

“We recommend that the inside of the dryer be cleaned as part of the bathroom cleaning schedule, which would mean turning off the dryer, then cleaning the hand chamber manually with disinfectant,” he said, adding that using paper towels is likely a safer option, provided that they are not already carrying some microorganisms.

“I think there is certainly the possibility of thinking your hands are clean when they may have been inoculated with micrograms while being dried,” Oberg said. “Our next study is to determine if microorganisms residing on the inside of the dryer readily transmit to the hand. I suspect that would be the case.”

https://www.healio.com/news/infectious-disease/20200803/bathroom-hand-dryers-can-harbor-spread-staphylococcus-fecal-matter?utm_source=selligent&utm_medium=email&utm_campaign=news&m_bt=1162769038120

UCSF Researchers Discover How Coronavirus Makes ‘Zombies’ Of Human Cells, Causes Them To Sprout Tentacles

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Fluorsecence microscopy image of human epithelial cells form the colon and infected with the novel coronovirus shows production of filopodia (white) extending our from the cell surface and containing viral particlea.

Most of us have already absorbed the idea that the coronavirus does some weird and sinister things to the human body that are unlike most other respiratory viruses known to man. But now a new study finds yet another unsettling thing that the virus appears to do to help spread from cell to cell.

A new study by an international team led by UC San Francisco finds that cells infected with SARS-CoV-2 quickly begin to grow new arms or dendrites — referred to clinically as filopodia — which are themselves studded with fresh virus particles. These filopodia then seek to reach into and through the walls of neighboring cells, thereby infecting them. And this appears to be a second mode that the virus has for replicating and spreading itself in the body.

As the LA Times reports via the study, up until now, researchers believed that this virus spread itself like most other viruses, by docking itself onto healthy cells, invading, and then turning those cells into copying machines. A team in UCSF’s Quantitative Biosciences Institute led by systems biologist Nevan Krogan launched a project in February to rapidly identify existing drugs and compounds that might treat or slow the spread of the coronavirus. They published initial findings in late April pointing to 10 existing drugs and experimental compounds that showed promise in lab settings when it came to targeting the human proteins this virus most needs to survive.

The latest study is an extension of that work, and Krogan is one of the lead authors of the paper published today in the journal Nature. The important new finding, Krogan and the team hope, will lead to some rapid study of several existing cancer treatments that themselves inhibit the growth of filopedia — thereby shutting down this second means that the virus is using to invade cells.

“It’s just so sinister that the virus uses other mechanisms to infect other cells before it kills the cell,” Krogan says, speaking to the LA Times.

Krogan says that while other viruses — including HIV and the family of viruses that cause smallpox — also use filopedia as mechanisms of spreading infection, the way this virus so rapidly prompts the growth of these tentacles is highly unusual. And the shape of them, branching off the cell and each other like trees, is also apparently strange. Other infectious diseases like HIV don’t cause these kinds of prolific, mutant growths.

Expanding the earlier list of promising drugs, the latest study points to seven cancer drugs already in use that could prove effective against COVID-19. Those include a drug already being used to treat acute myeloid leukemia called Xospata (generic name: gilteritinib); the experimental drug Silmitasertib, which is being studied as a treatment for bile duct cancer and one form of childhood brain cancer; and ralimetinib, another cancer drug which was developed by Eli Lilly to treat multiple forms of cancer.

“We’ve tested a number of these kinase inhibitors and some are better than remdesivir,” Krogan says, via the Milwaukee Journal-Sentinel.

Another experimental drug called Dinaciclib was found by the research team to stop the virus’s assault on a family of kinases called CDKs, which are responsible for cell growth and dealing with DNA damage.

Other infectious disease researchers are just waking up to the revelations of the paper, but most reactions seem fairly excited. While much research is being done on shutting down virus proteins, Krogan’s field of study, called proteomics, instead focuses on the less-likely-to-mutate human proteins involved in helping the virus do its dirty work.

“This paper shows just how completely the virus is able to rewire all of the signals going on inside the cell,” says University of Wisconsin-Madison medical professor Andrew Mehle to the Journal-Sentinel. “That’s really remarkable and it’s something that occurs very rapidly (as soon as two hours after cells are infected).”

And Lynne Cassimeris, a professor of biological sciences at Lehigh University, calls the latest findings “an amazing leap.” “We know that the virus has to be manipulating these human proteins,” Cassimeris says. “Now we have a list of what is changing over time.”

While Krogan’s lab at UCSF got this research off the ground just as the pandemic was emerging in February, there were 70 authors listed on the latest paper, with Krogan as the lead. The work was also done by scientists at Mt. Sinai Hospital in New York, Rocky Mountain Labs in Montana, the Pasteur Institute in Paris, and the University of Freiburg in Germany

https://sfist.com/2020/06/26/ucsf-researchers-discover-how-coronavirus-makes-zombies-of-human-cells-causes-them-to-sprout/

Thanks to Kebmodee for bringing this to the It’s Interesting community.

After saving his own life with a repurposed drug, a Professor David Fajgenbaum reviews every drug being tried against Covid-19

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By Ryan Prior

Every morning, Dr. David Fajgenbaum takes three life-saving pills. He wakes up his 21-month-old daughter Amelia to help feed her. He usually grabs some Greek yogurt to eat quickly before sitting down in his home office.

Then he spends most of the next 14 hours leading dozens of fellow researchers and volunteers in a systematic review of all the drugs that physicians and researchers have used so far to treat Covid-19. His team has already pored over more than 8,000 papers on how to treat coronavirus patients.

The 35-year-old associate professor at the University of Pennsylvania Perelman School of Medicine leads the school’s Center for Cytokine Storm Treatment & Laboratory. For the last few years, he has dedicated his life to studying Castleman disease, a rare condition that nearly claimed his life.

Against epic odds, he found a drug that saved his own life six years ago, by creating a collaborative method for organizing medical research that could be applicable to thousands of human diseases.

But after seeing how the same types of flares of immune-signaling cells, called cytokine storms, kill both Castleman and Covid-19 patients alike, his lab has devoted nearly all of its resources to aiding doctors fighting the pandemic.

During a cytokine storm, the body’s overactive immune response begins to attack its own cells rather than just the virus. When that inflammatory response occurs in Covid-19 patients, cytokines are often the culprit for the severe lung damage, organ failure, blood clots or pneumonia that kills them.

Having personal experience tamping down his own cytokine responses gives him a unique insight.
“I’m alive because of a repurposed drug,” he said.

Now, repurposing old drugs to fight similar symptoms caused by a novel virus has become a global imperative.


Researchers from Fajgenbaum’s lab gather in a video call to discuss Covid-19 treatment data.

A global repository for Covid-19 treatment data

Researchers working with his lab have reviewed published data on more than 150 drugs doctors around the world have to treat nearly 50,000 patients diagnosed with Covid-19. They’ve made their analysis public in a database called the Covid-19 Registry of Off-label & New Agents (or CORONA for short).

It’s a central repository of all available data in scientific journals on all the therapies used so far to curb the pandemic. This information can help doctors treat patients and tell researchers how to build clinical trials.

The team’s process resembles that of the coordination Fajgenbaum used as a medical student to discover that he could repurpose Sirolimus, an immunosuppressant drug approved for kidney transplant patients, to prevent his body from producing deadly flares of immune-signaling cells called cytokines.

The 13 members of Fajgenbaum’s lab recruited dozens of other scientific colleagues to join their coronavirus effort. And what this group is finding has ramifications for scientists globally.

Based on their database, the team published the first systematic review of Covid-19 treatments in the journal Infectious Diseases and Therapy in May.

In that first analysis of the data, the team reviewed 2,706 journal articles published on the topic between December 1, 2019, and March 27, 2020. Just 155 studies met the team’s criteria for being included in the meta-review based on standards such as the size of the cohort, the nature of the study and the end points researchers chose for concluding their inquiries.

“It’s frustrating because we all want a drug that works for everyone,” he said. But that isn’t happening because the coronavirus affects people in ways that are much more complex.

They’re sorting through oceans of data

The first key thing to consider, Fajgenbaum said, was the huge variety of Covid-19 patient experiences. It’s hard to zero in on one particular therapy because there can be such significant differences in the timing of when the drug is administered, how severely Covid-19 strikes a given individual and the stage at which the disease has progressed.

Any change in one of those variables can render an otherwise effective drug impotent. But with massive amounts of patients, the clinical data was bearing out a few noticeable themes, he said.

First, the Covid-19 patients with more severe cytokine storms were more likely to need drugs targeted toward suppressing the immune system. Those with less severe cytokine storms were likely to benefit from an immune-boosting drug.

Outside of drugs designed to boost or suppress the immune system, another major category is antiviral therapies. Various antivirals hit the “viral cascade,” Fajgenbaum said. Some work by stopping the virus from infecting cells, others by halting replication within cells. Other antivirals act in between cells and the virus.

Keeping the database is a huge undertaking, given how stunning the pace of global scientific progress and collaboration has been in the face of the disease’s human toll.

“We set the really ambitious goal of just getting this started,” Fajgenbaum said.

In the three months since the cutoff date for their first paper, the team has reviewed more than 5,000 additional papers published by scientists around the world.

One of their biggest challenges has been fitting the puzzle pieces of the different studies. With each study designed differently, one data set can’t necessarily be grafted neatly onto another. That’s especially tricky when most people diagnosed with Covid-19 eventually get better anyway. It’s hard to parse out if a particular drug was effective and saved lives.

The goal of the CORONA database isn’t to find a wonder drug per se, but to help design better clinical trials that can establish a real cause-and-effect relationship between a drug agent and an individual’s survival.

In the war against the coronavirus, Fajgenbaum hopes CORONA aims to help light the way so the heavy artillery on the front lines can better know what to shoot at Covid-19.

“It’s hard to fight a war if you’re not keeping track of what weapons are being used against the enemy,” he said.


Shown here is one of the researchers’ computer screens as they review Covid-19 treatment data while on a video call. The left side shows a spreadsheet where they tabulate data from the studies. The right side shows the study they’re currently analyzing.

They’re collaborating with FDA analysts

Fajgenbaum’s CORONA database dovetails with ongoing work at the US Food and Drug Administration. For years, the agency has been developing an app called CURE ID, a platform designed to help health care providers capture novel uses of already approved drugs.

The app launched in December with two goals in mind: The first was to help advise physicians searching for new treatment ideas, prescription guidelines and emergency use advisories for drugs across hundreds of diseases. The agency’s second aim was to build a structure by which health providers in the trenches could quickly input anonymized information about their patients so that other doctors around the world could quickly see whether they had been successful using an off-label drug.

The app was ready just in time for the pandemic, and Fajgenbaum gave the keynote speech at its launch.

“It’s really been a terrific collaboration,” said a health policy analyst with the FDA. “His life follows very much the model we hope to use.”

Now that he and his team are working on the coronavirus, the urgency of their partnership has strengthened.

“Nobody wants to go to a database with no data in it,” the analyst said. “Rather than reinventing the wheel, he was kind enough to provide all his data.”

And while the CORONA database project is primarily intended to aid researchers, it’s tapping into major currents in health economics that explain weak points in the way the public and private sector develop therapies together.

“Covid-19 illustrates a market failure in how we build vaccines,” said Amitabh Chandra, a health economist with joint appointments as a professor at the Harvard Kennedy School and Harvard Business School. “We haven’t given firms the correct incentives to make vaccines before a pandemic. Vaccines are very hard to test before the pandemic hits.”

There aren’t old vaccines sitting on a shelf waiting to be dusted off to save the world from the coronavirus. But there are hundreds of FDA-approved drugs at your local pharmacy that can save lives immediately.

When teaching classes, Chandra uses a 2017 New York Times story profiling Fajgenbaum to illustrate the value of drug repurposing and motivate his students to think boldly about how to create economic incentives to cure diseases, particularly when a “invisible medicine” might be right under your nose.

“There’s no substitute for a good story to get people motivated,” he said.
Many drugs are beginning to stand out.

The combination of antivirals lopinavir and ritonavir is the Covid-19 treatment protocol with the most number of studies published so far. As of mid-June, the team had looked at papers on that drug pairing involving more than 4,500 patients.

Next, corticosteroids have shown particular promise, making appearances in studies with another 4,000 patients. At the cellular level, antivirals work for a variety of reasons, each with its own specialty in attacking the virus at different points in its life cycle. Corticosteroids are different, however.

“Steroids tend to act the same, with replicating cortisol,” Fajgenbaum said.

He feels particularly elated about a recent United Kingdom-based study on the steroid dexamethasone. The study garnered headlines for its result showing that a low-dose 10-day regimen of the drug could reduce the risk of death by a third among hospitalized patients requiring ventilation.

In their spreadsheets, the numbers around dexamethasone were like a beacon.
“We built CORONA to help uncover something like dexamethasone,” he said. “It’s a cheap repurposed drug that’s been around for 60 years. This is what it’s all about.”

Studies need rigor

Because Covid-19 is so new, many of the studies are observational or anecdotal. These types of studies obviously matter as scientists are building a foundation of knowledge.

But the best insights come from running double-blind placebo-controlled studies. One shortfall is that many of the published studies just don’t have the level of rigor to inform larger-scale scientific decision-making.

“There are a lot of biases in these observational studies,” Fajgenbaum said.
One drug, the anti-malarial drug hydroxychloroquine, has famously received a lot of boosterism from US President Donald Trump. But in the published studies available for Fajgenbaum’s team to review, the drug hasn’t outperformed others.

Two French studies on hydroxychloroquine drew red flags for the University of Pennsylvania-based team because of the clinical end point the researchers chose: the time when the coronavirus cleared the body. It can be problematic to base an argument for a drug’s success only on that particular metric, because it leaves out crucial details from a person’s longer-term experience following infection.

“‘Virally cured’ is a challenging term,” Fajgenbaum said. “We don’t know if they’re discharged how they fared after leaving the hospital.”

On top of that, the reviewers were skeptical because the virus took a long time to leave the patients’ bodies, which they refer to as “a high time to viral clearance.”

That indicator that could suggest the drug was slow to take effect, or that other factors, including the patient’s own immune system, played a larger role in expelling the pathogen.

Know how to sort through the data

With dozens of people working full time to sort through thousands of studies, it’s obviously impossible for a single frontline health provider to keep abreast of all there is to know about Covid-19 while also treating patients at the same time.

It’s even harder for the average person following the story in the news, especially if you’re not equipped with a graduate degree in statistical analysis.

“Covid threw the world in flux,” said Sheila Pierson, associate director for clinical research at the CSTL. A biostatistician originally hired to study Castleman disease, she’s accepted the new mission along with her colleagues.

“There’s a lot of great science being done,” she explained. With that pace of innovation, it’s incredibly difficult for the average person to stay up to date, so the CORONA database helps everyone with a little extra scientific literacy amid headlines about new treatments that induce a form of intellectual whiplash.

“You should rely on multiple news sources,” Pierson said, in order to sort through what may appear to be conflated messages about whether a certain drug works or not for a certain group of people.

“It’s difficult when you’re only looking at one person’s view of a drug,” she said. “Look for a different write-up and a different view.”

He’s repeating the same methods that saved his life

As of June 27, Fajgenbaum has lived free of Castleman’s cytokine storms for 77.72 months. His last Castleman relapse ended on January 5, 2014. He’s a living experiment, and in his personal accounting he won’t round up to the next full month. Each new day is a precious moment with a daughter he feared he’d never meet.

The doctor and researcher remains immune compromised and won’t take risks with the coronavirus.
He hasn’t set foot in a building other than his home since March 13. And his life still relies on siltuximab and chemotherapy infusions administered monthly through a chest port.

“I’m reminded every time I touch the port in my chest of the cytokine storms I had,” he said. “I want so badly to solve (Covid-19) the way I did with Castleman. I have the same sense of urgency.”

Castleman disease nearly killed Fajgenbaum five times in his 20s while he was working his way through University of Pennsylvania’s Perelman School of Medicine and then earning an MBA at the University of Pennsylvania’s Wharton School.

Each time, the deadly disease triggered cytokine storms that led to multiple organ failure.

But the young man created a global organization to rally doctors, scientists and patients toward finding a cure. With intense study and brilliant partners, he zeroed in on an already available immunosupressant that could be repurposed to save his life.

Last year he published his memoir, “Chasing My Cure,” detailing a journey in which at one point a priest was brought to his hospital room to give his last rites.

Fajgenbaum’s story reads likes the teaser for a hit Netflix series. But if it were a show, all of that is really just season one. Because, spoiler alert — then a global pandemic hit.

A year ago you might have thought what the writers threw at him in a second season might be a bit unrealistic. But this project is the obvious next step.

“I see myself bringing our experiences with Castleman now over to the global fight against corona,” he said.

https://www.cnn.com/2020/06/27/health/coronavirus-treatment-fajgenbaum-drug-review-scn-wellness/index.html

Chemists develop foolproof new test to track the fats we eat

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Philip Britz-McKibbin, Professor of Chemistry & Chemical Biology, McMaster University Credit: JD Howell, McMaster University

A team of researchers at McMaster University has developed a reliable and accurate blood test to track individual fat intake, a tool that could guide public health policy on healthy eating.

Establishing reliable guidelines has been a significant challenge for nutritional epidemiologists until now, because they have to rely on study participants faithfully recording their own consumption, creating results that are prone to human error and selective reporting, particularly when in the case of high-fat diets.

For the study, published in the Journal of Lipid Research, chemists developed a test, which detects specific non-esterified fatty acids (NEFAs), a type of circulating free fatty acid that can be measured using a small volume of blood sample.

“Epidemiologists need better ways to reliably assess dietary intake when developing nutritional recommendations,” says Philip Britz-McKibbin, professor in the Department of Chemistry & Chemical Biology at McMaster University and lead author of the study.

“The food we consume is highly complex and difficult to measure when relying on self-reporting or memory recall, particularly in the case of dietary fats. There are thousands of chemicals that we are exposed to in foods, both processed and natural,” he says.

The study was a combination of two research projects Britz-McKibbin conducted with Sonia Anand in the Department of Medicine and Stuart Phillips in the Department of Kinesiology.

Researchers first assessed the habitual diet of pregnant women in their second trimester, an important development stage for the fetus. The women, some of whom were taking omega-3 fish oil supplements, were asked to report on their average consumption of oily fish and full-fat dairy and were then tested with the new technology. Their study also monitored changes in omega-3 NEFAs in women following high-dose omega-3 fish oil supplementation as compared to a placebo.

Researchers were able to prove that certain blood NEFAs closely matched the diets and/or supplements the women had reported, suggesting the dietary biomarkers may serve as an objective tool for assessment of fat intake.

“Fat intake is among the most controversial aspects of nutritional public health policies given previously flawed low-fat diet recommendations, and the growing popularity of low-carb/high-fat ketogenic based diets” says Britz-McKibbin. “If we can measure it reliably, we can begin to study such questions as: Should pregnant women take fish oil? Are women deficient in certain dietary fats? Does a certain diet or supplement lead to better health outcomes for their babies?”

Researchers plan to study what impact NEFAs and other metabolites associated with dietary exposures during pregnancy, might have on childhood health outcomes in relation to the obesity, metabolic syndrome and chronic disease risk later in life.

https://medicalxpress.com/news/2020-05-chemists-foolproof-track-fats.html

Spain’s oldest woman (113 years old) speaks about surviving COVID

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Branyas lives in Olot, a city in Catalonia.

By Jack Guy and Al Goodman

A 113-year-old woman, thought to be the oldest in Spain, has said she feels fine after surviving a brush with coronavirus.

Video footage of Maria Branyas, who was born on March 4 1907, shows the super-centenarian speaking to the director of the care home where she lives in Olot, Catalonia.

“In terms of my health I am fine, with the same minor annoyances that anyone can have,” said Branyas in the video. It was recorded Monday, a spokeswoman for the care home told CNN.

Branyas recovered after a mild case of Covid-19. Her battle started shortly after her family visited her on March 4 to celebrate her 113th birthday, the spokeswoman said.

The family has not been able to visit in person since then. Branyas has lived for 18 years in her own private room at the Santa Maria del Tura nursing home, which is run by the Institute of the Order of San Jose of Gerona, affiliated with the Roman Catholic Church, the spokeswoman said.

Branyas was born in San Francisco in the United States, where her father worked as a journalist, reports the AFP news agency.

Over the course of her long life she has survived two world wars as well as the 1918 flu pandemic, which killed more than 50 million people around the world.

Although Branyas recovered from coronavirus, two residents of the same home died of it. The situation at the care home has since improved, said the spokeswoman.

Spain’s state of emergency, in effect since March 14, has strict confinement measures that remain in place. But with the infection and death rates now declining, the government has lifted some lockdown measures in certain parts of the country, on what it says will be a gradual reopening of activity.

But the initial lifting of these restrictions did not apply to Olot, where Branyas lives.

https://www.cnn.com/2020/05/13/europe/spain-oldest-woman-coronavirus-survivor-scli-intl/index.html

The presence of receptors for SARS-CoV-2 on a wide variety of human cells supports the idea that COVID-19 is not just a respiratory disease but an illness across multiple organs.

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Human cell types within corresponding organs that express the genes for both ACE2 and CTSL (green dot) or both ACE2 and TMPRSS2 (orange dot).

by Chris Baraniuk

When the SARS-CoV-2 virus enters the human body, it breaks into cells with the help of two proteins that it finds there, ACE2 and TMPRSS2. While there has been much discussion of viral infection in gut and lung cells, researchers have dug into massive gene expression datasets to show that other potential target cells also producing ACE2 and TMPRSS2 are scattered throughout the body—including in the heart, bladder, pancreas, kidney, and nose. There are even some in the eye and brain.

The results, published in a preprint on bioRxiv April 21, show that such cells are strikingly abundant. Many are epithelial cells, which line the outer surface of organs. The new findings add to an emerging picture of SARS-CoV-2 as a virus that can target cells in many places in the human body, rather than being focused on a particular organ or part of the respiratory tract.

Cardiologist Frank Ruschitzka at the University Hospital of Zürich and colleagues separately published a letter in The Lancet April 17 in which they described how virus particles had been found in the vascular endothelium, a thin layer of cells lining blood vessels in various organs of the body, for instance.

“This is not just a virus pneumonia,” Ruschitzka, who was not involved in the latest study, tells The Scientist, referring to COVID-19. “This is a disease like we have never seen before—it is not an influenza, it hits the vessels all over, it hits the heart as well.”

To uncover the locations of cells bearing ACE2 and TMPRSS2, the preprint researchers turned to the Human Cell Atlas, a project that has allowed scientists to pool together data on human cells since 2016.

By scouring single-cell sequencing records of around 1.2 million individual cells from human tissue samples, the team was able to find out which of those cells produce both ACE2 and TMPRSS2, and note their locations in the body. The analysis used 16 unpublished datasets of lung and airway cells and 91 published datasets spanning a range of human organs.

Coauthor Christoph Muus, a graduate student at Harvard University and the Broad Institute, explains that while the data show cells in many locations in the body produce SARS-CoV-2 receptors, it’s not certain that the virus can infect all of those tissues.

“Expressing the receptor is a necessary condition but not necessarily a sufficient condition,” he says. For example, potential target cells were found in the testes, but scientists still don’t know if SARS-CoV-2 infects and replicates in that part of the body.

Jeremy Kamil, a virologist at Louisiana State University Health Shreveport, says the preprint provides important details about the human body that may help scientists understand how SARS-CoV-2 infects hosts. By finding viral protein fragments in tissue samples from patients who died because of COVID-19, scientists might be able to firm up which organs are genuine sites of infection, he adds.

“I’d say this paper gives people a roadmap at where you might want to look in the body to understand where this virus is going,” he says.

One limitation of the work is that relatively little metadata about the people who donated tissue samples were available for the various datasets, though information about age and gender were included in many. The researchers don’t know, for example, whether there was an ethnicity bias in the data, whether patients had pre-existing conditions, or whether they were taking any medications. All of these things could affect gene expression in particular cells.

Smoking status was available for a subset of the data, and the team used this to show that smoking is correlated with a greater expression of the ACE2 gene in the upper airway, but lower expression in certain lung cells. Further research is needed to understand whether this affects smokers’ susceptibility to COVID-19. Data from China suggest that smokers are 14 times more likely to develop a severe form of the disease.

Some researchers from the same group using similar data have also recently published papers in Cell and Nature. In those cases, the researchers focused on certain groups of cells. The study reported in Nature examined cells potentially involved in viral transmission and found that nasal epithelial cells, in particular, were associated with expression of ACE2 and TMPRSS2. The authors report that the virus might exploit cells that secrete fluids in the nasal passage, which might help it spread from one person to another in droplets released, say, when someone sneezes.

The Cell study, meanwhile, also found ACE2 and TMPRSS2 transcripts in nasal, gut, and lung cells but the researchers also found that the protein interferon activated ACE2 expression in vitro. The human body uses interferon to fight infections, so it is not clear whether the protein is of overall benefit or detriment to COVID-19 patients.

The use of so many different data sources backs up the validity of the preprint authors’ findings, says Marta Gaglia, a molecular biologist at Tufts University. She agrees with the researchers that discovering ACE2- and TMPRSS2-producing cells in various places around the body does not prove the virus can always infect such cells.

“I think the reality is that most of the problems come from the lung,” she adds. Plus, while doctors treating COVID-19 patients may detect problems in multiple organs, those issues might not necessarily be caused directly by SARS-CoV-2 infection, says Gaglia. A problematic immune system response, for instance, could damage certain tissues in the body as an indirect consequence of viral infection.

https://www.the-scientist.com/news-opinion/receptors-for-sars-cov-2-present-in-wide-variety-of-human-cells-67496?utm_campaign=TS_DAILY%20NEWSLETTER_2020&utm_source=hs_email&utm_medium=email&utm_content=87213170&_hsenc=p2ANqtz-_vGzY0JSZbqON-CbrWnU2wp22vNPAa-zcPDPoSZR69MA0qXhi3ukYIXekJJKZ_A_GfMi8lV1cuO5y2DnnkhV-rdYFrPQ&_hsmi=87213170

New Medical Device to Detect Precancerous Lesions in the Esophagus Wins 2020 Edison Award

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A medical device based on technology developed by three faculty members from Case Western Reserve University and University Hospitals Cleveland Medical Center (UH) has won a prestigious 2020 Edison Best New Product Award.

EsoCheck, a device designed to help detect precancerous changes in the esophagus, was named a “Silver” winner of the 2020 Edison Best New Product Awards in the “Medical/Dental – Testing Solutions” subcategory.

Esophageal adenocarcinomas have increased more than five-fold in recent years and are a highly lethal cancer, with less than 20% 5-year survival. These cancers arise from a precursor lesion of Barrett’s esophagus (BE), which is an abnormal cell type that arises in the lower esophagus.

EsoCheck is a swallowable balloon-based device that, in a simple five-minute outpatient exam, can collect cells from the lower region of the esophagus to help determine if Barrett’s disease is present. Unlike endoscopy, the current method for examining the esophagus, EsoCheck does not require a patient to undergo sedation, lose a day of work or need a companion for transportation.

The EsoCheck device works together with EsoGuard, a companion molecular assay that tests the DNA from the cells retrieved by EsoCheck for the presence of genetic changes indicative of the presence or absence of Barrett’s disease.

Lucid Diagnostics, a subsidiary of New York-based PAVmed Inc., licensed the EsoCheck and EsoGuard technology through the Case Western Reserve University Technology Transfer Office in 2018.

The EsoCheck device and EsoGuard DNA test were co-invented by Amitabh Chak, MD, (Professor of Medicine at the Case Western Reserve School of Medicine and gastroenterologist at the University Hospitals Digestive Health Institute); Sanford Markowitz, MD, PhD, (Ingalls Professor of Cancer Genetics and Medicine at the School of Medicine and an oncologist at University Hospitals Seidman Cancer Center); and Joseph Willis, MD,(Professor of Pathology at the School of Medicine and Pathology Vice-Chair for translational research at UH).

The technology was developed as part of the Case Comprehensive Cancer Center’s GI SPORE (Gastrointestinal Specialized Program of Research Excellence) and BETRNet (Barrett’s Esophagus Translational Research Network) programs led by Markowitz and Chak, and was first tested in humans in a clinical trial led by Chak at University Hospitals.

Further support for the clinical assay development was derived from a National Cancer Institute award led by Willis. The development was also supported by the Case-Coulter partnership and the State of Ohio Third Frontier Technology Validation Start-up Fund.

Last fall, the new EsoCheck method for examining the esophagus received clearance from the U.S. Food and Drug Administration for clinical use, and, this February, the companion EsoGuard DNA test for Barrett’s detection received breakthrough designation from the FDA.

Since 1987, the Edison Awards, named after Thomas Alva Edison, have recognized some of the most innovative products and business leaders in the world. They’re among the most prestigious accolades, honoring excellence in new product and service development, marketing, design and innovation.

About University Hospitals / Cleveland, Ohio

Founded in 1866, University Hospitals serves the needs of patients through an integrated network of 18 hospitals, more than 50 health centers and outpatient facilities, and 200 physician offices in 16 counties throughout northern Ohio. The system’s flagship academic medical center, University Hospitals Cleveland Medical Center, located in Cleveland’s University Circle, is affiliated with Case Western Reserve University School of Medicine. The main campus also includes University Hospitals Rainbow Babies & Children’s Hospital, ranked among the top children’s hospitals in the nation; University Hospitals MacDonald Women’s Hospital, Ohio’s only hospital for women; University Hospitals Harrington Heart & Vascular Institute, a high-volume national referral center for complex cardiovascular procedures; and University Hospitals Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center. UH is home to some of the most prestigious clinical and research programs in the nation, including cancer, pediatrics, women’s health, orthopedics, radiology, neuroscience, cardiology and cardiovascular surgery, digestive health, transplantation and urology. UH Cleveland Medical Center is perennially among the highest performers in national ranking surveys, including “America’s Best Hospitals” from U.S. News & World Report. UH is also home to Harrington Discovery Institute at University Hospitals – part of The Harrington Project for Discovery & Development. UH is one of the largest employers in Northeast Ohio with 28,000 physicians and employees. Advancing the Science of Health and the Art of Compassion is UH’s vision for benefitting its patients into the future, and the organization’s unwavering mission is To Heal. To Teach. To Discover. Follow UH on LinkedIn, Facebook @UniversityHospitals and Twitter @UHhospitals. For more information, visit UHhospitals.org.

https://finance.yahoo.com/news/medical-device-developed-cwru-uh-123000489.html

Long Work Hours Linked to Greater Risk for Hypothyroidism

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by Rose Reeb

Increased weekly working hours are associated with a higher risk for hypothyroidism in workers with no evidence of thyroid autoimmunity, according to study results published in Thyroid.

To determine if long work hours are associated with thyroid function, researchers conducted a cross-sectional study using data from 2160 South Korean adults (69.9% men). Individuals who had provided blood and urine samples, were working ≥36 hours per week and <12 hours per day, were not pregnant, did not have a history of thyroid disease, did not have a positive thyroid peroxidase antibody test, did not have isolated hypothyroidism or hyperthyroidism, and were not missing relevant data were included.

Hypothyroidism was defined as a serum thyrotropin level above the upper reference limit with a normal or low free thyroxine level. Hyperthyroidism was defined as a serum thyrotropin level below the lower reference limit with a normal or high free thyroxine level.

The median age of the included individuals was 42.4 years (interquartile range, 33.0- 52.1). The median weekly number of work hours was 47.1 (interquartile range, 39.8-54.9) and 15.4% of included individuals were shift workers. Overall, hypothyroidism was observed in 2.1% and hyperthyroidism was observed in 2.9% of the cohort.

Rates of both hypothyroidism (3.6%) and hyperthyroidism (3.5%) were highest in the group with the highest work hours (P =.03 for trend). The mean number of work hours per week in euthyroid, hypothyroid, and hyperthyroid individuals were 49.5±0.3, 53.4±1.5, and 51.6±1.6 hours, respectively (P =.012). There was a significant association between hypothyroidism and longer work hours per week, even after adjusting for all biological and lifestyle covariates (adjusted odds ratio [aOR], 1.46; 95% CI, 1.12-1.90) and excluding outliers in number of work hours per week (aOR, 1.99; 95% CI, 1.19-3.31) and individuals with overt thyroid dysfunction (aOR, 1.44; 95% CI, 1.11-1.88). Hyperthyroidism was not significantly associated with the number of hours worked per week.

Moreover, hypothyroidism was approximately 2.6 times more prevalent in individuals who worked 53 to 83 hours per week compared with those who worked 36 to 42 hours per week.

As the study was cross-sectional and observational in nature, causation could not be determined. The researchers suggested that “[f]urther research is needed to clarify the causal relationship and the underlying mechanism” of hypothyroidism in connection to longer working hours.

Reference

Lee YK, Lee D-E, Hwangbo Y, Lee YJ, Kim HC, Lee EK. Long work hours are associated with hypothyroidism: a cross-sectional study with population-representative data [published online March 31, 2020]. Thyroid. doi:10.1089/thy.2019.0709