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Published8 hours agoSharecloseShare pageCopy linkAbout sharingImage source, Getty ImagesBy Smitha MundasadHealth reporter A “game-changing” immunotherapy drug proven to delay the development of type 1 diabetes has been approved by regulators in the USA. Experts say teplizumab marks a “new era” in treatment, tackling the root cause of the condition for the first time, rather than just the symptoms.It works by reprogramming the immune system to stop it mistakenly attacking pancreatic cells which produce insulin.It is likely to pave the way for approval decisions in other countries. About 8.7 million people have type 1 diabetes worldwide. In the UK the condition affects 400,000 people, including more than 29,000 children. ‘Taking away the burden’In type 1 diabetes, the immune system (that normally fights off bacteria and viruses) mistakenly attacks key cells in the pancreas which produce insulin. Insulin is crucial, helping the body use sugar for energy, and most current treatments focus on people checking their blood sugars and taking insulin – by injection or infusion – every day.In 2019, a trial showed the drug delayed some people at high risk of the condition from developing it for an average of three years. Experts say this delay can be very significant, particularly for young people who would not have to take daily insulin or monitor their sugars as intensively for that period of time. They suggest people could also spend more years with their blood sugars in a healthy range, offering more time to be protected from the complications of high blood sugars such as kidney or eye disease. Image source, Beth BaldwinBeth Baldwin’s son Peter died after a diabetic ketoacidosis emergency in 2014. He had undiagnosed type 1 diabetes and his body was shutting down. He was just 13.Beth said: “A drug like this would be life-changing. “You cannot stop people getting type 1 diabetes for now. But delaying the onset…. would be phenomenal – particularly for children. “It means three years of not having to intensively manage the condition, and it may delay it long enough for more research to take place. “It is a huge step forward.” Beth now works with the charity JDRF UK to increase awareness of the signs of type 1 diabetes, including feeling very thirsty, urinating more than usual, feeling very tired and losing weight without trying.You can read more about Peter’s story here.Rachel Connor, from the JDRF UK charity, which part-funded the trial, said: “This is a game-changer. To me this is the start of a new era for the treatment of type 1 diabetes. “It is the first time we are able to get to the heart of why the condition develops and help change the process, so we are not just treating the symptoms any more. “Once we can do that, we can find other ways to do it better and for longer.”Type 1 diabetes: ‘People don’t know how hard it is’.What is diabetes?Diabetes is a lifelong condition that causes a person’s blood sugar level to become too high.There are two main types:type 1 – where the body’s immune system attacks and destroys the cells that produce insulintype 2 – where the body does not produce enough insulin, or the body’s cells do not react to insulinType 2 diabetes is far more common than type 1.Source: NHSMore on this storyStopping type 1 diabetes from birth11 July 2018Type 1 diabetes: ‘People don’t know how hard it is’9 MayPioneering type 1 diabetes therapy safe9 August 2017Related Internet LinksWhat is type 1 diabetes – NHS.websiteAbout us JDRF, the type 1 diabetes charity.websiteThe BBC is not responsible for the content of external sites.

Scientists  have developed a strategy that could give a boost to the development of pyridine-containing drugs and organic functional materials.
In chemicals used in agriculture, as well as in pharmaceuticals and a variety of materials, pyridines are often found as so-called functional units which decisively determine the chemical properties of substances. Pyridines belong to the group of ring-shaped carbon-hydrogen (C-H) compounds (“heterocycles”), and they contain a nitrogen atom (N). For chemists, the direct functionalization of the carbon-hydrogen bonds (C-H bonds) of pyridines is a straightforward approach to designing and modifying complex molecules, including in the final stage of the synthesis sequence.
This latter means that active ingredients can be chemically modified without having to build them up anew. The functionalization of the pyridine in a certain position in relation to the nitrogen atom — in the difficult-to-access “meta-position” — is extremely challenging and rare. A team of researchers headed by Prof. Armido Studer at the Institute of Organic Chemistry at the University of Münster has developed a new strategy for getting various functional groups into the meta-position of pyridines. Their study has now been published in the journal Science.
The chemists use a temporary de-aromatization of the pyridine: its electronic properties are reversed, producing a stable intermediary product — a dienamine. By means of radical and polar chemistry, the researchers are able, with a high degree of selectivity, to get a large number of fluorinated alkanes, as well as a series of “electron-poor substituents” (electrophiles), into the meta-position. These transformations also include medically and agrochemically relevant functionalities such astrifluoromethyl and halogen groups. “The important thing,” says Dr. Hui Cao, a postdoc in the Studer working group, “is that the functionalized dienamine intermediary products are easily re-aromatized to meta-functionalized pyridines under acidic conditions.”
His colleague Dr. Qiang Cheng adds, “The high degree of efficiency, the broad range of applications and the meta-selectivity of our approach enables twelve different types of drugs to be functionalized.” In addition, the team developed processes in which drugs can be transformed directly into trifluoromethyl and chlorine-substituted derivatives — in so-called one-pot reactions, which involve little effort and take place in one single reaction vessel. For this purpose, the chemists use inexpensive, commercially available reagents. “Our study supplies an answer to the unsolved problem of functionalizing pyridine in the meta-position,” says Armido Studer. “We believe that this publication will give a significant boost to the development of medicines containing pyridines and of organic functional materials.”
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A Ludwig Cancer Research study has revealed a single protein expressed at high levels by cancer cells across a broad range of malignancies that erects a multifaceted barrier to anti-cancer immune responses in mouse models of cancer and so shields tumors from immune detection and destruction.
Led by Ludwig Lausanne’s Douglas Hanahan, two former scientists in his lab Qiqun Zeng and Sadegh Saghafinia, and graduate student Agnieszka Chryplewicz, the study also describes a signature of gene expression induced by the protein, named FMRP, that encompasses 156 distinct genes and predicts poor patient survival across multiple types of cancer. The findings, reported in the journal Science, could with further development inform the selection of patients likely to benefit from immunotherapies and the development of new therapies of this kind for multiple types of cancer.
“Our study has detailed a previously unknown and apparently common mechanism by which malignant cells shut down anti-cancer immune responses,” said Hanahan, distinguished scholar at the Ludwig Institute for Cancer Research Lausanne Branch. “We have shown that the hyperexpression of FMRP, which we and others have previously linked to tumor progression, doesn’t directly drive cancer cell proliferation and tumor growth. Rather, it supports the ability of malignant cells to manipulate the types and functional states of immune cells around them in a manner that very effectively subverts immune attack.”
A protein primarily expressed in neurons, FMRP has been extensively studied as a factor whose loss of expression during embryogenesis is associated with the neuro-developmental disorder fragile X syndrome, which causes severe intellectual disability. Functionally, FMRP is known to help stabilize the messenger RNA readouts of genes in cells and to regulate translation of that information into proteins. But its role in cancer progression was less clear.
The researchers began by showing that FMRP levels are elevated across multiple types of tumors. To examine its function in cancer, they applied CRISPR-Cas9 gene editing to delete FMR1, the gene that encodes FMRP, in mouse cancer cell lines. They then used the engineered cell lines to generate mouse models of pancreatic, colon, melanoma and breast tumors and compared them to matching tumors that retained their FMR1 genes, using mice that either had or lacked intact immune systems.
While all tumors grew similarly in culture and in immunodeficient mice, the ones that lacked the FMR1 gene were severely impaired in mice with competent immune systems. They were also heavily infiltrated with helper and cytotoxic T cells, which play a central role in anti-cancer immunity. Those with intact FMR1 genes, on the other hand, progressed aggressively and were by comparison so-called “immune deserts” — devoid of anti-tumor T cells. When T cells were removed from the FMR1-deficient tumors, they resumed growth, suggesting that FMRP supports tumor progression through its effects on the immune response.

Researchers at the Beckman Institute for Advanced Science and Technology developed a new method to ‘see’ the fine structure and chemical composition of a human cell with unmatched clarity and precision.
It’s why Jaws swam out of sight for more than an hour and hints at the glamour of giftwrap. In movie theaters, living rooms, and even labs, the thrill of the unseen can be counted on to keep us guessing. But when it comes to the hidden chemical world of cells, scientists need no longer wonder.
Inspired by this same thrill, researchers at the Beckman Institute for Advanced Science and Technology developed an innovative way to ‘see’ the fine structure and chemical composition of a human cell with unmatched clarity and precision. Their technique, which appeared in PNAS earlier this week, takes a creative — and counterintuitive — approach to signal detection.
“Biology is one of the most exciting sciences of our time because there has always been a divide between what we can see and what we cannot see,” said Rohit Bhargava, a professor of bioengineering at the University of Illinois Urbana-Champaign who led the study.
As the smallest functional units in our bodies, cells have long commanded the attention of researchers interested in determining what they’re made of and where each element resides. Together, the “what” and the “where” form an all-purpose cellular blueprint that can be used to study biology, chemistry, materials, and more.
Before this study, obtaining a high-resolution copy of that blueprint ranked among the impossible.

Personal sensing data could help monitor and alleviate stress among resident physicians, although privacy concerns over who sees the information and for what purposes must be addressed, according to collaborative research from Cornell Tech.
Burnout in all types of workplaces is on the rise in the U.S., where the “Great Resignation” and “silent quitting” have entered the lexicon in recent years. This is especially true in the health care industry, which has been strained beyond measure due to the COVID-19 pandemic.
Stress is physical as well as mental, and evidence of stress can be measured through the use of smartphones, wearables and personal computers. But data collection and analysis — and the larger questions of who should have access to that information, and for what purpose — raise myriad sociotechnical questions.
“We’ve looked at whether we can measure stress in workplaces using these types of devices, but do these individuals actually want this kind of system? That was the motivation for us to talk to those actual workers,” said Daniel Adler, co-lead author with fellow doctoral student Emily Tseng of “Burnout and the Quantified Workplace: Tensions Around Personal Sensing Interventions for Stress in Resident Physicians,” published Nov. 11 Proceedings of the ACM on Human-Computer Interaction.
The paper is being presented at the ACM Conference on Computer-Supported Cooperative Work (CSCW) and Social Computing, taking place virtually Nov. 8-22.
Adler and Tseng worked with senior author Tanzeem Choudhury, the Roger and Joelle Burnell Professor in Integrated Health and Technology at the Jacobs Technion-Cornell Institute at Cornell Tech. Contributors came from Zucker School of Medicine at Hofstra/Northwell Health and Zucker Hillside Hospital.

Your entire medical journey lives in digital health records, but how do you know if those records are wrong, incomplete or missing important information? That’s the focus of research done by Varadraj Gurupur, associate professor in UCF’s School of Global Health Management and Informatics.
His latest project created an algorithm that can predict and measure the incompleteness of electronic health records — in everything from your lab results to disease diagnoses, medical history to prescription records.
Missing information in the electronic health records (EHR) that hospitals and doctor’s offices keep is like a leaking pipe, he says. If you don’t know where the leak is, you can’t fix it, and soon the house can flood. The same dangers can happen in healthcare. A recent study by Gurupur revealed that a critical percent of digital health records contained missing information.
His algorithm uses mathematics and computer science to answer, “Where is the water leaking?” he says. The analysis performed by Gurupur and his team found that the level of incompleteness per year varies and there is not a pattern of where missing data happens. His algorithm helps identify attributes that have a higher tendency to be incomplete — the areas of the water pipe that are more vulnerable and can break more frequently.
His previous studies have documented that the biggest reasons for missing health information are communication and education. Communication between patients and their providers isn’t always clear — especially if the patient is interacting with a healthcare professional who does not speak their native language. Cultural barriers may keep patients from sharing important information with their providers. Digital technology also creates its own challenges. Providers may not fill out electronic records until day’s end — and forget what the patient said or not have it accurately in their notes. Hospitals and clinics switch electronic health record systems, requiring extensive new retraining which results in a learning curve for providers. Some healthcare workers, especially those who did not grow up with technology, may not be adept at using EHRs.
“Missing health information can sometimes be as simple as a person who isn’t sure what button to push in the new system,” Gurupur says.

The brains of people with Down syndrome develop the same neurodegenerative tangles and plaques associated with Alzheimer’s disease and frequently demonstrate signs of the neurodegenerative disorder in their forties or fifties. A new study from researchers at UC San Francisco shows that these tangles and plaques are driven by the same amyloid beta (Aß) and tau prions that they showed are behind Alzheimer’s disease in 2019.
Prions begin as normal proteins that become misshapen and self-propagate. They spread through tissue like an infection by forcing normal proteins to adopt the same misfolded shape. In both Alzheimer’s and Down syndrome, as Aß and tau prions accumulate in the brain, they cause neurological dysfunction that often manifests as dementia.
Tau tangles and Aß plaques are evident in most people with Down syndrome by age 40, according to the National Institute on Aging, with at least 50% of this population developing Alzheimer’s as they age.
The new study, published Nov. 7, 2022, in Proceedings of the National Academy of Sciences, highlights how a better understanding of Down syndrome can lead to new insights about Alzheimer’s, as well.
“Here you have two diseases — Down syndrome and Alzheimer’s disease — that have entirely different causes, and yet we see the same disease biology. It’s really surprising,” said Stanley Prusiner, MD, the study’s senior author, who was awarded the Nobel Prize in 1997 for his discovery of prions.
Down syndrome is the most common neurodegenerative disease among younger people in the United States, while Alzheimer’s is the most common among adults.

After statins, the next leading class of medications for managing cholesterol are PCSK9 inhibitors. These highly effective agents help the body pull excess cholesterol from the blood, but unlike statins, which are available as oral agents, PCSK9 inhibitors can only be administered as shots, creating barriers to their use.
Now, a new study from investigators at University Hospitals (UH) and Case Western Reserve University School of Medicine describes an orally administered small-molecule drug that reduces PCSK9 levels and lowers cholesterol in animal models by 70%. Published in Cell Reports, the findings represent a previously unrecognized strategy for managing cholesterol and may also impact cancer treatments.
“Cholesterol lowering is one of the most important therapies we have to prolong life and protect people from heart disease, which is still the number one cause of morbidity and mortality in the Western world,” said Jonathan S. Stamler, MD, senior author, President, Harrington Discovery Institute at UH, Robert S. and Sylvia K. Reitman Family Foundation Distinguished Professor of Cardiovascular Innovation, and Professor of Medicine and Biochemistry at UH and Case Western Reserve School of Medicine.
“Statins only lower cholesterol so far. This is a drug class that we think would represent a new way to lower cholesterol, a new way to hit PCSK9.”
Study Findings
Central to cholesterol regulation are LDL receptors, which sit at the surface of liver cells and remove cholesterol from the blood, thereby lowering serum levels. PCSK9 in the bloodstream controls the number of LDL receptors by marking them for degradation. Therefore, agents that inhibit PCSK9 increase the number of LDL receptors that remove cholesterol.
Nitric oxide is a molecule that is known to prevent heart attacks by dilating blood vessels. In the new study, Stamler and colleagues show that nitric oxide can also target and inhibit PCSK9, thus lowering cholesterol. They identify a small molecule drug that functions to increase nitric oxide inactivation of PCSK9. Mice treated with the drug display a 70% reduction in LDL “bad” cholesterol.
Beyond Cholesterol to Cancer
In addition to impacting the field of cholesterol metabolism, the findings may impact patients with cancer, as emerging evidence suggests targeting PCSK9 can improve the efficacy of cancer immunotherapies.
“PCSK9 not only targets LDL receptors for degradation, it also mediates the degradation of MHC 1 on lymphocytes, which is used for recognition of cancer cells” said Stamler. “PCSK9 is effectively preventing your lymphocytes from recognizing cancer cells. So, if you inhibit PCSK9, you can boost the body’s cancer surveillance. There may be an opportunity one day to apply these new drugs to that need.”
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Researchers have identified five genetic variants that increasingly raise a person’s risk of becoming nearsighted the longer they stay in school. A team led by Jeremy Guggenheim of Cardiff University, United Kingdom, published these findings November 17 in the open access journal PLOS Genetics.
Nearsighted vision is associated with a range of eye disorders, making it a leading cause of irreversible vision impairment in older individuals. People often become nearsighted as children, however, and the condition appears to result from a mix of genetics, too little time spent outdoors and many years of education. Genetic studies have identified more than 450 genetic variants associated with an increased risk of nearsightedness, but few have been shown to increase risk specifically in people with the associated lifestyle factors. In the new study, researchers used genetic and health data from more than 340,000 participants with European ancestry. They performed a genome-wide study to identify genetic variants that make people more susceptible to becoming nearsighted in combination with intensive schooling.
The study yielded five genetic variants that progressively increased the risk of becoming nearsighted for individuals, the more time they spent in school — especially for people who had attained education at the university level. Three of these variants were previously unknown, while two were found in studies of East Asian cohorts, where about 80% of children become nearsighted. For comparison, about 30% of children develop nearsightedness in the West. The researchers said that these findings provide new insights into the biological pathways that cause nearsightedness, but more research is needed to understand how those pathways interact with lifestyle factors to cause the condition.
Guggenheim adds, “As well as requiring the need for glasses or contact lenses, myopia is a leading cause of uncorrectable visual impairment. Building on our previous research linking education and myopia, the new study identifies 5 genes associated with myopia development whose effects are amplified by additional years spent in education.”
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Many estimates of how strongly traits and diseases share genetic signals may be inflated, according to a new UCLA-led study that indicates current methods for assessing genetic relationships between traits fail to account for mating patterns.
Through the use of powerful genome sequencing technology, scientists in recent years have sought to understand the genetic associations between traits and disease risk, hoping that discoveries of shared genetics could point to clues for tackling diseases. However, UCLA researchers said their new study, published Nov. 17 in Science, provides caution against relying too heavily on genetic correlation estimates. They say that such estimates are confounded by non-biological factors more than has been previously appreciated.
Genetic correlation estimates typically assume that mating is random. But in the real world, partners tend to pair up because of many shared interests and social structures. As a result, some genetic correlations in previous work that have been attributed to shared biology may instead represent incorrect statistical assumptions. For example, previous estimates of genetic overlap between body mass index (BMI) and educational attainment are likely to reflect this type of population structure, induced by “cross-trait assortative mating,” or how individuals of one trait tend to partner with individuals of another trait.
The study authors said genetic correlation estimates deserve more scrutiny, since these estimates been used to predict disease risk, glean for clues for potential therapies, inform diagnostic practices, and shape arguments about human behavior and societal issues. The authors said some in the scientific community have placed too much emphasis on genetic correlation estimates based on the idea that studying genes, because they are unalterable, can overcome confounding factors.
“If you just look at two traits that are elevated in a group of people, you can’t conclude that they’re there for the same reason,” said lead author Richard Border, a postdoctoral researcher in statistical genetics at UCLA. “But there’s been a kind of assumption that if you can track this back to genes, then you would have the causal story.”
Based on their analysis of two large databases of spousal traits, researchers found that cross-trait assortative mating is strongly associated with genetic correlation estimates and plausibly accounts for a “substantial” portion of genetic correlation estimates.
“Cross-trait assortative mating has affected all of our genomes and caused interesting correlations between DNA you inherit from your mother and DNA you inherit from your father across the whole genome,” said study co-author Noah Zaitlen, a professor of computational medicine and neurology at UCLA Health.
The researchers also examined genetic correlation estimates of psychiatric disorders, which have sparked debate in the psychiatric community because they appear to show genetic relationships among disorders that seemingly have little similarity, such as attention-deficit hyperactivity disorder and schizophrenia. The researchers found that genetic correlations for a number of unrelated traits could be plausibly attributed to cross-trait assortative mating and imperfect diagnostic practices. On the other hand, their analysis found stronger links for some pairs of traits, like anxiety disorders and major depression, suggesting that there truly is at least some shared biology.
“But even when there is a real signal there, we’re still suggesting that we’re overestimating the extent of that sharing,” Border said.
Other study authors include Georgios Athanasiadis, Alfonso Buil, Andrew J. Schork, Na Cai, Alexander I. Young, Thomas Werge, Jonathan Flint, Kenneth S. Kendler, Sriram Sankararaman, and Andy Dahl. The authors declared no competing interests. Please see the study for a full list of funders.