Tag: health

Lithium in drinking water linked to negative effects on human health

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Key takeaways:

  • Increased risk for autism spectrum disorder was associated with 7.36 µg/L lithium exposure.
  • Increased risk for schizophrenia spectrum disorder was associated with 5.8 µg/L lithium exposure.

NEW YORK — Lithium exposure in drinking water was associated with potentially detrimental effects on human health, including increased risk for autism spectrum disorder and schizophrenia spectrum disorder, according to researchers.

“At the state hospital we deal with a lot of the sickest patients,” Sonja M. Johnson, DO, a fourth-year psychiatry resident at Indiana University Health, told Healio at the American Psychiatric Association annual meeting. “Lithium is an awesome medication, and it does a lot of great things. We always hear the phrase, ‘That’s so good. Put it in the water!’ I mean, they did it with fluoride, right?”

Andrea Patterson, MD, also a fourth-year resident in psychiatry, and colleagues at Indiana University School of Medicine performed a systematic review of 26 studies with data from five continents to determine whether higher levels of environmental lithium in the water supply poses a risk to human health.

Sonja M. Johnson

“Mental health is still kind of taboo in our area, but water is important, and people drink water,” Johnson said. “The question was, can we help everyone without making everyone take medicine?”

Of the reviewed studies, 12 showed that lithium exposure through drinking water had the potential for negative effects on the nervous, cardiovascular, endocrine, lymphatic, urinary and integumentary systems and could affect newborns to adults and pregnant women.

Although researchers reported that at 7 µg/L, lithium begins to have protective factors against suicide, they noted that at 7.36 µg/L it was associated with autism spectrum disorder, and at 5.8 µg/L with schizophrenia.

“Given this information, any lithium added to the U.S. water supply for protective reasons would inevitably increase the risk of harm,” researchers wrote.

“When you ask a question, sometimes the answer is no,” Johnson said. “That’s still an answer, and that’s still pretty awesome, because if you don’t ask you don’t know.”

Sources/Disclosures

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Source: 

Patterson A, et al. Too much of a good thing? Detrimental health effects linked to environmental lithium exposure through drinking water: A systematic review. Presented at: American Psychiatric Association annual meeting; May 4-8, 2024; New York.

Disclosures: Johnson reported no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

https://www.healio.com/news/psychiatry/20240507/lithium-in-drinking-water-linked-to-negative-effects-on-human-health?utm_source=SMC&utm_medium=email&utm_campaign=Lunch%20Break&utm_content=Psychiatry

Google Street View predicts heart disease risk based on neighborhood features

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Researchers have used Google Street View to study hundreds of elements of the built environment, including buildings, green spaces, pavements and roads, and how these elements relate to each other and influence coronary artery disease in people living in these neighborhoods.

Their findings, published in the European Heart Journal today (Thursday), show that these factors can predict 63% of the variation in the risk of coronary heart disease from one area to another.

Coronary heart disease, where a build-up of fatty substances in the coronary arteries interrupts the blood supply to the heart, is one of the most common forms of cardiovascular disease.

Researchers say that using Google Street View can help provide an overview of physical environmental risk factors in the built and natural environments that could help not only in understanding risk factors in these environments, but ultimately help towards building or adapting towns and cities to make them healthier places to live.

The study was led by Prof. Sadeer Al-Kindi and Prof. Sanjay Rajagopalan from University Hospitals Harrington Heart & Vascular Institute and Case Western Reserve University, Ohio, USA, and Dr. Zhuo Chen, a post-doctoral fellow in Prof. Rajagopalan’s laboratory.

Prof. Rajagopalan said: “We have always been interested in how the environment, both the built and natural environment, influences cardiovascular disease. Here in America, they say that the zip code is a better predictor of heart disease than even personal measures of health. However, to investigate how the environment influences large populations in multiple cities is no mean task. Hence, we used machine vision-based approaches to assess the links between the built environment and coronary heart disease prevalence in US cities.”

The study included more than half a million Google Street View images of Detroit, Michigan; Kansas City, Missouri; Cleveland, Ohio; Brownsville, Texas; Fremont, California; Bellevue, Washington State; and Denver, Colorado. Researchers also collected data on rates of coronary heart disease according to ‘census tracts’. These are areas smaller than a US zip code that are home to an average of 4,000 people. The researchers used an approach called a convolutional neural network; a type of artificial intelligence that can recognize and analyze patterns in images to make predictions.

The research revealed that features of the built environment visible on Google Street View images could predict 63% of the variation in coronary heart disease between these small regions of US cities.

Prof. Al-Kindi added: “We also used an approach called attention mapping, which highlights some of the important regions in the image, to provide a semi-qualitative interpretation of some of the thousands of features that may be important in coronary heart disease. For instance, features like green space and walkable roads were associated with lower risk, while other features, such as poorly paved roads, were associated with higher risk. However, these findings need further investigation.

“We’ve shown that we can use computer vision approaches to help identify environmental factors influencing cardiovascular risk and this could play a role in guiding heart-healthy urban planning. The fact that we can do this at scale is something that is absolutely unique and important for urban planning.”

“With upcoming challenges including climate change and a shifting demographic, where close to 70% of the world’s population will live in urban environments, there is a compelling need to understand urban environments at scale, using computer vision approaches that can provide exquisite detail at an unparalleled level,” said Prof. Rajagopalan.

In an accompanying editorial, Dr. Rohan Khera from Yale University School of Medicine, USA said: “The association of residential location with outcomes often supersedes that of known biological risk factors. This is often summarised with the expression that a person’s postal code is a bigger determinant of their health than their genetic code. However, our ability to appropriately classify environmental risk factors has relied on population surveys that track wealth, pollution, and community resources.

“The study by Chen and colleagues presents a novel and more comprehensive evaluation of the built environment. This work creatively leverages Google’s panoramic street-view imagery that supplements its widely used map application.

“… an AI-enhanced approach to studying the physical environment and its association with cardiovascular health highlights that across our communities, measures of cardiovascular health are strongly encoded in merely the visual appearance of our neighborhoods. It is critical to use this information wisely, both in defining strategic priorities for identifying vulnerable communities and in redoubling efforts to improve cardiovascular health in communities that need it most.”

https://www.msn.com/en-gb/health/other/google-street-view-predicts-heart-disease-risk-based-on-neighborhood-features/ar-BB1kFeqv

New test for oral cancer

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Aaron Weinberg of Case Western Reserve University

Oral cancers and precancerous mouth lesions are considered especially difficult to diagnose early and accurately.

For one, biopsies are expensive, invasive, stressful for the patient and can lead to complications. They’re also not feasible if repeated screenings of the same lesion are required.

But a team of researchers, led by a clinician scientist at Case Western Reserve University School of Dental Medicine, has discovered a noninvasive, low-cost test to detect oral cancer, monitor precancerous lesions and determine when a biopsy is warranted.

Their findings, published online March 4 in the journal Cell Reports Medicine are based on a scoring system linked to the levels of two proteins in cells brushed from suspicious oral lesions of patients at dental clinics or the ear, nose and throat department at University Hospitals (UH).

One of the proteins (human beta defensin 3 or hBD-3) is expressed at high levels in early-stage oral cancer, while the second (hBD-2) is low or unchanged.

The ratio of hBD-3 to hBD-2 in the lesion site—over the ratio of the two proteins on the opposite, normal site—generates a score, called the beta defensin index (BDI).

A score above a predetermined threshold implies cancer; anything below does not. Determining the levels of the proteins and quantifying the BDI is done routinely in a lab.

The BDI was independently validated using identical protocols at CWRU/UH, University of Cincinnati Medical Center and West Virginia University School of Dentistry.

“When we first discovered hBD-3, we saw it acted as a ‘good guy,’ involved in wound-healing and killing microbes,” said Aaron Weinberg, chair of the Department of Biological Sciences at the Case Western Reserve School of Dental Medicine and the study’s lead researcher. “When we found it was regulated the same way certain cells grow uncontrollably, we started studying hBD-3 in the context of oral cancer.

“Imagine our surprise when this Dr. Jekyll turned out to be Mr. Hyde,” he said. “We found it was not only promoting tumor growth but was overexpressed in the early stages of the disease, while another member, hBD-2, wasn’t changing. This difference in levels of expression of the two proteins compared to the opposite side in the same patient led us to examine the BDI’s ability to distinguish cancer from benign lesions.”

Weinberg credits School of Dental Medicine instructor Santosh Ghosh for navigating the BDI scoring process.

Head and neck cancer (HNC), of which oral cancer is about 90%, is the seventh-most prevalent malignancy in the world, and developing countries are witnessing a rise in its incidence. HNC makes up about 5% of all cancers worldwide and 3% of all malignancies in the United States, according to the National Institutes of Health. There are about 640,000 cases of HNC per year, resulting in about 350,000 deaths worldwide, mainly in socioeconomically disadvantaged populations and underserved communities.

The study’s lab-based approach, which is now patented, can reduce biopsies in primary care clinics by 95% because it can tell clinicians who actually needs a biopsy, said Weinberg, also secondarily appointed in the Departments of Pathology and Otolaryngology at Case Western Reserve School of Medicine. The test can also be used in developing countries where oral cancer is rampant and pathology services are questionable or lacking, he said.

The positive data from the lab-based approach has inspired the development of a point-of-care (POC) device in collaboration with Umut Gurkan, the Wilbert J. Austin Professor of Engineering at the Case School of Engineering. The POC diagnostic approach measures the protein ratio and could be used directly in a clinic, providing results within half-hour.

Working through Case Western Reserve’s Technology Transfer Office, a patent for the device is pending, setting up possible manufacturing and clinical validation as a next step.

Discovery, clinical validation studies and POC technology development were supported by the National Institute of Dental and Craniofacial Research, National Cancer Institute, Case Coulter Translational Research Partnership and Ohio Third Frontier Technology Validation and Start-Up Fund.

Case Western Reserve University-led research team discovers new method to test for oral cancer

Researchers identify new therapeutic approach targeting astrocytes, the brain’s most abundant cells

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A team led by scientists at Case Western Reserve University School of Medicine has identified a new therapeutic approach for combating neurodegenerative diseases, offering hope of improved treatments for Alzheimer’s disease, Parkinson’s disease, Vanishing White Matter disease and multiple sclerosis, among others. 

Neurodegenerative diseases, which affect millions of people worldwide, occur when nerve cells in the brain or nervous system lose function over time and ultimately die, according to the National Institutes of Health. Alzheimer’s disease and Parkinson’s disease are the most common.

The research team’s new study, published online Feb. 20 in the journal Nature Neuroscience, focused on astrocytes—the brain’s most abundant cells, which normally support healthy brain function. Growing evidence indicates astrocytes can switch to a harmful state that increases nerve-cell loss in neurodegenerative diseases.

The researchers created a new cellular technique to test thousands of possible medications for their ability to prevent these rogue astrocytes from forming. 

“By harnessing the power of high-throughput drug-screening, we’ve identified a key protein regulator that, when inhibited, can prevent the formation of harmful astrocytes,” said Benjamin Clayton, lead author and National Multiple Sclerosis Society career transition fellow in the laboratory of Paul Tesar at the Case Western Reserve School of Medicine.

They found that blocking the activity of a particular protein, HDAC3, may prevent the development of dangerous astrocytes. The scientists discovered that by administering medications that specifically target HDAC3, they were able to prevent the development of dangerous astrocytes and significantly increase the survival of nerve cells in mouse models.

“This research establishes a platform for discovering therapies to control diseased astrocytes and highlights the therapeutic potential of regulating astrocyte states to treat neurodegenerative diseases,” said Tesar, the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics and the study’s principal investigator.  

Tesar, also director of the School of Medicine’s Institute for Glial Sciences, said more research needs to be done before patients might benefit from the promising approach. But, he said, their findings could lead to the creation of novel therapies that disarm harmful astrocytes and support neuroprotection—perhaps improving the lives of people with neurodegenerative illnesses in the future.

“Therapies for neurodegenerative disease typically target the nerve cells directly,” Tesar said, “but here we asked if fixing the damaging effects of astrocytes could provide therapeutic benefit. Our findings redefine the landscape of neurodegenerative disease treatment and open the door to a new era of astrocyte targeting medicines.”

Additional contributing researchers from the Case Western Reserve School of Medicine, and from the George Washington School of Medicine, The Ohio State University and the University of Tampa included James Kristell, Kevin Allan, Erin Cohn, Yuka Maeno-Hikichi, Annalise Sturno, Alexis Kerr, Elizabeth Shick, Molly Karl, Eric Garrison, Robert Miller, Andrew Jerome, Jesse Sepeda, Andrew Sas, Benjamin Segal, and Eric Freundt.

The research was supported by grants from the National Institutes of Health, National Multiple Sclerosis Society and Hartwell Foundation, and philanthropic support by sTF5 Care and the R. Blane & Claudia Walter, Long, Goodman, Geller and Weidenthal families.

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