Publisher Health

Newly developed risk scores synthesize genetic information into an easy-to-interpret metric that could help clinicians identify young children most at risk of developing obesity.
The study, led by researchers at Penn State, used novel statistical methods to establish scoring criteria using data collected from young children. The research also demonstrates that robust results are attainable from studies that are orders-of-magnitude smaller than typical genetic studies when comprehensive data is collected over time and used in conjunction with powerful statistical tools.
“About 18% of children in the United States are obese, and 6% are severely obese,” said Sarah Craig, assistant research professor of biology at Penn State. “If we can identify children most at risk, we might be able to prevent obesity from developing in the first place. In this study, we produced risk scores based on genetic information that clinicians could potentially use to identify young children who would most benefit from intervention strategies.”
This study is part of a larger project called INSIGHT (Intervention Nurses Start Infants Growing on Healthy Trajectories), coordinated through the Penn State Health Milton S. Hershey Medical Center, in which researchers and clinicians work together to identify biological and social risk factors for obesity and the impacts of responsive parenting interventions during a child’s early life. The research team collected longitudinal data — periodically 8 times between birth and three years of age — including weight, height, and behavioral and environmental variables — on nearly 300 children. They also collected a blood sample for genetic analyses from each of the children, which served as the basis for developing risk scores. The team published their results in a paper appearing in the journal Econometrics and Statistics.
The risk scores — called “polygenic risk scores” because they are based on many genetic locations across the genome — distill vast genetic information into an easy-to-grasp number. Typically, the scores incorporate information from a number of single nucleotide polymorphisms (SNPs), or locations in the genome where single letters of the DNA alphabet can vary among people, that are most related to the metrics of interest — in this case, growth rates and obesity.
“Previous attempts to produce polygenic risk scores for obesity were developed using genetic information from adults or older children and include anywhere from a hundred to two million SNPs,” said Kateryna Makova, professor of biology and Verne M. Willaman Chair of Life Sciences at Penn State. “Such high numbers are challenging and potentially expensive to consistently reproduce, especially in a clinical setting. We produced two score options with far fewer SNPs — one with 24 and one with 5 — that nonetheless can provide valuable information to researchers and clinicians.”
The research team used novel statistical techniques from a field called functional data analysis to identify the SNPs most related to obesity, which were then incorporated into the scores.

A research team led by University of California, Irvine has discovered new neural circuits that regulate spatial learning and memory in the brain’s hippocampal formation. The team identified novel functional roles of new circuit connections between the venal CA1 region and dorsal CA3 regions of the hippocampus and demonstrated that genetic inactivation of this projection impairs object-related spatial learning and memory, but does not modulate anxiety-related behaviors.
The study, titled “Non-canonical projections to the hippocampal CA3 regulate spatial learning and memory by modulating the feedforward hippocampal trisynaptic pathway,” was published today in PLOS Biology.
The hippocampus is not a homogenous brain area. The septotemporal axis, along which the trisynaptic pathway is located, separates the dorsal region of the hippocampus, which is more involved in learning, memory and spatial navigation, and the ventral region, which plays a role in emotional behavior. The trisynaptic’s feedforward, unidirectional circuit organization is well documented, but the connectivity across septal to temporal regions is less well described.
“Our findings extend the knowledge of hippocampal connectivity and its relation to learning and memory processes across the septotemporal axis and provide a circuit foundation to explore these novel functional roles,” said Xiangmin Xu, PhD, Chancellor’s Fellow and professor of anatomy and neurobiology, and director for the Center for Neural Circuit Mapping (CNCM) at the UCI School of Medicine. “The new hippocampal circuit mechanism is highly relevant to treating learning and memory disorders, including Alzheimer’s disease.”
Building on their earlier work, Xu and his team used multiple viral tracers, including monosynaptic rabies retrograde tracing and herpes (H129)-based anterograde tracing to establish new hippocampal CA1 projections to CA3. Robust mapping results showed that CA1 inputs to CA3 run opposite the trisynaptic pathway and in a temporal to septal direction. They also found that genetic inactivation of the CA1 to CA3 projection impaired object-related spatial learning and memory, but did not modulate anxiety-related behaviors.
“The emergence of viral-genetic mapping techniques enhances our ability to determine the detailed complexity of brain circuity,” Xu said. “Our study was made possible by the new viral genetic tools developed by our CNCM investigators at UCI. We are developing these new viral tracers as brain mapping tools, which we plan to share through our center for use by the neuroscience community.”
Other UCI members of the research team include Xiaoxiao Lin, UCI anatomy and neurobiology graduate student and first author of the paper; biomedical engineering undergraduate Michelle Amalraj; Crisylle Blanton and neurobiology undergraduate researcher Brenda Avila. Other significant contributors to the study include Douglas A. Nitz, PhD, professor and chair of the Department of Cognitive Science at the University of California, San Diego; and Todd C. Holmes, PhD, physiology and biophysics professor in the UCI School of Medicine.
This work was supported by National Institutes of Health BRAIN Initiative grants NS078434 and MH120020; and an NIH R35 grant GM127102.
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Researchers have developed an optical biopsy system that can distinguish between cancerous and healthy liver tissue. The new technology could make it easier to diagnose liver cancer, which is the sixth most common cancer globally.
“The instrument is designed to be compatible with the needles currently used for liver biopsies,” said Evgenii Zherebtsov, a member of the research team from Orel State University in Russia. “It could thus one day help surgeons more precisely navigate the biopsy instrument to decrease the number of errors in taking tissue samples that are used for diagnosis.”
In the Optica Publishing Group journal Biomedical Optics Express, the researchers report that the optical biopsy system can reliably distinguish between cancerous and healthy cells in mouse models. The system also showed promise in preliminary tests conducted in people with suspected liver cancer.
“Optical biopsy methods like the one we developed make it possible to differentiate healthy and tumor tissues with a high degree of accuracy,” said Elena V. Potapova, who was co-first author of the paper with Zherebtsov. “Although our system was specifically designed for use in abdominal surgery, our results show that similar technologies could be useful for other medical applications.”
Responding to a clinical need
The researchers designed the new device after the surgeons with which they were collaborating noted how difficult it is to perform needle biopsies in exactly the right location. Early-stage tumors can be hard to pinpoint when inserting a tiny hollow needle into the liver to acquire a tissue sample. If the needle is placed incorrectly and misses the tumor, it could lead to an incorrect diagnosis.

With visual cues and complex steps, at-home coronavirus tests are often inaccessible to blind people. But some low- and high-tech workarounds could help.Christy Smith has never been tested for the coronavirus. As a blind person, she can’t drive to testing sites near her home in St. Louis, and they are too far away for her to walk. Alternative options — public transportation, ride share apps or having a friend drive her to a test site — would put others at risk for exposure.The rapid tests that millions of other people are taking at home, which require precisely plunking liquid drops into tiny spaces and have no Braille guides, are also inaccessible to Ms. Smith.Many people who are blind or have limited vision are not being tested as often as they would like — and some are staying isolated because testing is too difficult.“Not all of us have access to somebody sighted to help with things on a regular basis,” Ms. Smith said. “It’s kind of a mix of frustration and just feeling a bit helpless,” she added.When Ms. Smith’s husband, who is also blind, fell sick with a sore throat, stuffy nose and fever last fall, both of them isolated at home until his symptoms disappeared. They never found out what pathogen caused the infection.Some blind people manage to take at-home tests with the help of video call apps, like Be My Eyes and Aira. These services pair blind individuals with a sighted person who can describe their surroundings and guide them through a test, step by step.But these interactions are difficult, and not everyone who is blind owns a smartphone or is able to use a smartphone. What’s more, relying on others can erode a blind person’s privacy and independence.“It’s your personal health information,” said Martin Wingfield, the head of brand at the Royal National Institute of Blind People in Britain. “You should be the first to know.”Mr. Wingfield is part of a team that created a home pregnancy test that delivers results through raised bumps that can be felt by a blind person. The prototype uses a battery-operated motor that transforms chemical changes on a strip into raised bumps.Known as a lateral flow assay, it is the same type of test used to detect the coronavirus at home. So in theory, the institute’s prototype could be modified to make at-home coronavirus tests more accessible, Mr. Wingfield said. The cost of so-called tactile tests would be roughly $20 to $30, he said, though manufacturers might be able to make them for less.Another way to deliver test results could be through a change in smell or temperature, according to Hoby Wedler, a blind chemist and entrepreneur. Currently, most at-home tests use substances that change color after a chemical reaction. But “there are all sorts of things we can have these indicators do other than change color,” he said.Although a change in scent might not be useful for Covid patients, who often lose their sense of smell, Dr. Wedler argued that other types of at-home tests could be made more accessible through concepts like this.Hoby Wedler, a chemist and entrepreneur, has spent his life as an advocate for the blind. He believes new science could employ temperature or smell changes to make coronavirus tests more accessible.Bryan Meltz for The New York TimesCoronavirus tests can be tricky to carry out. Many require the user to dispense liquid into small holes and not touch the testing strip.“Blind people do most of what they do using touch in some way,” said Kim Charlson, the immediate past president of the American Council of the Blind. “Even guiding the swab into the tube without touching something or touching it can be very difficult, even for people who have been blind for a long time and are pretty confident.”Ms. Charlson has worked with health agencies to create more walk-up test site options, and she is now asking manufacturers to make more accessible home tests.The Coronavirus Pandemic: Key Things to KnowCard 1 of 6The global surge.

Women vaccinated against COVID-19 transfer SARS-CoV-2 antibodies to their breastfed infants, potentially giving their babies passive immunity against the coronavirus, according to University of Massachusetts Amherst research.
The study, published in the journal Obstetrics & Gynecology, measured the immune response to the COVID-19 mRNA vaccine in both breast milk and the stools of breastfed infants.
“This research is the first to detect SARS-CoV-2 antibodies in stool samples from infants of vaccinated mothers,” says lead author Vignesh Narayanaswamy, a Ph.D. candidate in the breastmilk research lab of senior author Kathleen Arcaro, professor of environmental toxicology in the Department of Veterinary and Animal Sciences. “This is really important because women want to know whether their babies have these antibodies, and our study shows that antibodies are being transferred via breast milk. Providing this compelling evidence is motivation for women to continue breastfeeding after they receive the vaccine.”
Narayanaswamy notes another important takeaway: the antibodies were detected in infants regardless of age — from 1.5 months old to 23 months old.
Thirty lactating women from across the U.S. — most of them healthcare workers — were enrolled in the study. They received the COVID-19 mRNA vaccine between January and April 2021. The women provided breast milk samples before they were vaccinated, across two to three weeks after their first vaccine dose and across three weeks after the second dose. They also gave samples of their blood, spotted on cards, 19 days after the first dose and 21 days after the second dose. Infant stool samples were collected 21 days after the mothers’ second vaccination. Pre-pandemic samples of breast milk, dried blood spots and infant stools were used as controls for the study.
The samples were tested for receptor-binding domain (RBD)-specific immunoglobulin (Ig)A and IgG antibodies. In the breast milk samples, anti-RBD IgG antibodies were found to neutralize the protein spike of SARS-CoV-2, as well as four variants. A significant increase in cytokine levels also revealed the immune response in breast milk samples.
Anti-RBD IgG and anti-RBD IgA antibodies were detected in 33% and 30% of infant stool samples, respectively. The levels of antibodies correlated with the vaccine side effects the mother experienced.
“Women who did feel sick from the vaccine was associated with greater antibodies in the infant stool,” Arcaro says. “So you might have felt badly, but that was a benefit for your infant.”
The study, Arcaro says, received no specific funding and was partially driven by the participants themselves, who were familiar with Arcaro’s wide-ranging breast milk research, including the New Moms Wellness Study and BRCA gene-mutation research that Narayanaswamy focuses on.
While lactating and pregnant women were urged to be vaccinated, no pregnant or breastfeeding women were included in the vaccine trials, Arcaro notes. Findings show that “even if you had COVID, there is a benefit for women to get the vaccine.”
The research team included Arcaro’s UMass colleagues Dominique Alfandari, Brian Pentecost and Sallie Schneider; Dr. Corina Schoen, assistant professor of obstetrics and gynecology at UMass Chan Medical School-Baystate; and Ryan Baker, a UMass Amherst undergraduate student.
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When scientists discovered DNA and learned how to control it, not only science but society was revolutionized. Today researchers and the medical industry routinely create artificial DNA structures for many purposes, including diagnosis and treatment of diseases.
Now an international research team reports to have created a powerful supermolecule with the potential to further revolutionize science.
The work is published in Nature Communications. Authors are from University of Southern Denmark (Denmark), Kent State University (USA), Copenhagen University (Denmark), Oxford University (UK) and ATDBio (UK). Lead authors are Chenguang Lou, associate professor, University of Southern Denmark and Hanbin Mao, professor, Kent State University, USA.
Next generation of nanotechnology
The researchers describe their supermolecule as a marriage between DNA and peptides.
DNA is one of the most important biomolecules, and so are peptides; peptide structures are used, among other things, to create artificial proteins and various nanostructures.

Fewer than 1 in 5 adults with Type 2 diabetes in the U.S. are meeting targets to reduce heart disease risk. Fortunately, available therapies can help when combined with new approaches that address social determinants of health and other barriers to care, according to a new American Heart Association scientific statement published today in the Association’s flagship journal Circulation. A scientific statement is an expert analysis of current research and may inform future clinical practice guidelines.
“This new scientific statement is an urgent call to action to follow the latest evidence-based approaches and to develop new best practices to advance Type 2 diabetes treatment and care and reduce CVD risk,” said Joshua J. Joseph, M.D., M.P.H., FAHA, chair of the statement writing group and an assistant professor of medicine in the division of endocrinology, diabetes and metabolism at The Ohio State University College of Medicine in Columbus, Ohio. “Far too few people — less than 20% of those with Type 2 diabetes — are successfully managing their heart disease risk, and far too many are struggling to stop smoking and lose weight, two key CVD risk factors. Health care professionals, the health care industry and broader community organizations all have an important role to play in supporting people with Type 2 diabetes.”
Type 2 diabetes is the most common form of diabetes, affecting more than 34 million people in the U.S., representing nearly 11% of the U.S. population, according to the U.S. Centers for Disease Control and Prevention’s 2020 National Diabetes Statistics Report, and cardiovascular disease (CVD) is the leading cause of death and disability among people with Type 2 diabetes (T2D). Type 2 diabetes occurs when the body is unable to efficiently use the insulin it makes or when the pancreas loses its capacity to produce insulin. People with T2D often have other cardiovascular disease risk factors, including overweight or obesity, high blood pressure or high cholesterol. Adults with T2D are twice as likely to die from CVD — including heart attacks, strokes and heart failure — compared to adults who do not have T2D.
The new scientific statement, based on the writing group’s extensive review of clinical trial results through June 2020, addresses the gap between existing evidence on how best to lower cardiovascular risk in people with T2D and the reality for people living with T2D. Targets to reduce CVD risk among people with T2D include managing blood glucose, blood pressure and cholesterol levels; increasing physical activity; healthy nutrition; obesity and weight management; not smoking; not drinking alcohol; and psychosocial care. Greater adherence to an overall healthy lifestyle among people with T2D is associated with a substantially lower risk of CVD and CVD mortality.
“In the United States, less than 1 in 5 adults with T2D not diagnosed with cardiovascular disease are meeting optimal T2D management goals of not smoking and achieving healthy levels of blood sugar, blood pressure and low-density lipoprotein (LDL) cholesterol, also known as ‘bad’ cholesterol,” Joseph said.
A surprisingly large proportion — as high as 90% — of factors to effectively manage CVD with T2D includes modifiable lifestyle and societal factors. “Social determinants of health, which includes health-related behaviors, socioeconomic factors, environmental factors and structural racism, have been recognized to have a profound impact on cardiovascular disease and Type 2 diabetes outcomes,” he said. “People with T2D face numerous barriers to health including access to care and equitable care, which must be considered when developing individualized care plans with our patients.”
Shared decision-making among patients and health care professionals is essential for successfully managing T2D and CVD. A comprehensive diabetes care plan should be tailored based on individual risks and benefits and in consideration the patient’s preferences; potential cost concerns; support to effectively manage T2D and take medications as prescribed, including diabetes self-management education and support; promotion and support of healthy lifestyle choices that improve cardiovascular health including nutrition and physical activity; and treatment for any other CVD risk factors.

A new study conducted in mice demonstrates precisely how triclosan, an antimicrobial found in many household items, including some toothpastes, toys and thousands of other products, can trigger gut inflammation.
Increasingly, research links triclosan with the gut microbiome and gut inflammation. A new study looks at the potential for combating damage to the intestine. The findings suggest new approaches for improving the diagnosis, prevention and treatment of inflammatory bowel disease.
An international team of researchers led by the University of North Carolina at Chapel Hill, the University of Massachusetts Amherst and Hong Kong Baptist University identified the bacteria, and even specific enzymes, that trigger triclosan’s harmful effects. Moreover, studies in mice suggest these bacterial enzymes can be blocked from driving intestinal damage.
The findings were published in Nature Communications.
“By identifying the culprit bacteria, new approaches could be developed for the diagnoses, prevention and treatment of inflammatory bowel diseases,” said study author Matthew Redinbo, a chemistry and microbiology professor at the UNC-Chapel Hill College of Arts & Sciences and UNC School of Medicine.
Previous research has shown triclosan’s toxicity, but the new study provides a closer look at the changes caused in the gut’s microscopic population.

A new study, published in Nature Communications and led by Imperial College London researchers, provides the first evidence of a protective role for these T cells. While previous studies have shown that T cells induced by other coronaviruses can recognise SARS-CoV-2, the new study examines for the first time how the presence of these T cells at the time of SARS-CoV-2 exposure influences whether someone becomes infected.
The researchers also say their findings provide a blueprint for a second-generation, universal vaccine that could prevent infection from current and future SARS-CoV-2 variants, including Omicron.
Dr Rhia Kundu, first author of the study, from Imperial’s National Heart & Lung Institute, says: “Being exposed to the SARS-CoV-2 virus doesn’t always result in infection, and we’ve been keen to understand why. We found that high levels of pre-existing T cells, created by the body when infected with other human coronaviruses like the common cold, can protect against COVID-19 infection.
“While this is an important discovery, it is only one form of protection, and I would stress that no one should rely on this alone. Instead, the best way to protect yourself against COVID-19 is to be fully vaccinated, including getting your booster dose.”
The study began in September 2020 when most people in the UK had neither been infected nor vaccinated against SARS-CoV-2. It included 52 people who lived with someone with PCR-confirmed SARS-CoV-2 infection and who had therefore been exposed to the virus. The participants did PCR tests at the outset and 4 and 7 days later, to determine if they developed an infection.
Blood samples from the 52 participants were taken within 1-6 days of them being exposed to the virus. This enabled the researchers to analyse the levels of pre-existing T cells induced by previous common cold coronavirus infections that also cross-recognise proteins of the SARS-CoV-2 virus [1].

An international research group at the RIKEN Cluster for Pioneering Research (CPR) has successfully treated cancer in mice using metal catalysts that assemble anticancer drugs together inside the body. Published in the scientific journal Nature Communications, the study is the first report of therapeutic in vivo synthetic chemistry being used to make anticancer substances where they are needed simply by injecting their ingredients through a vein. Because this technique avoids indiscriminate tissue damage, it is expected to have a significant impact on cancer treatment.
Aside from effectiveness at killing cancer cells, a major challenge to cancer chemotherapy is how to mitigate the toxic side effects on the body. Drugs that can damage cancer cells can damage non-cancerous cells as well, and the negative side effects of chemotherapy can cause permanent and debilitating damage. Current methods for reducing these side effects include selective delivery of anticancer drugs to cancer tissue (drug delivery) and conversion of non-toxic compounds (prodrugs) into toxic compounds nearby the cancerous tissue.
Katsunori Tanaka at RIKEN CPR, who led the new study, has developed a method for activating prodrugs using transition-metal catalysis inside the body. When the catalyst is injected into an organism, it usually has no effect because it is destroyed by antioxidants such as glutathione. By placing the transition-metal catalysts inside special pockets within a protein, Tanaka and his colleagues have been able to avoid this problem and stabilize the catalytic function in vivo, thus ensuring that the chemical reaction can proceed efficiently in the body. For this technique to work, the catalyst needs to selectively find its way to the cancer. As in their previous studies, the team targeted the catalyst to the cancer by attaching chains of cancer-binding sugar molecules to the surface of the carrier protein. Using these techniques, Tanaka’s group succeeded in inhibiting cancer growth and metastasis, as well as reducing the side effects. The new study is a proof of concept in which cancer in mice was treated by actually assembling anticancer drugs inside the body near the cancer cells. “In the past, we used similar methods to attach anticancer drugs to tumors,” says Tanaka, “but here, we were able to avoid putting any toxic drugs into the body at all.”
Noting that the basic skeleton of most anticancer drugs contains a benzene ring, the researchers started by making benzene rings inside the body using transition-metal catalysts. “No one believed that artificially synthesizing benzene rings inside the body was possible, but I was confident that we could do it based on our previous achievements,” says Tanaka. Using a transition metal-catalyzed complex designed for selective delivery to cancerous tissues, they succeeded in efficiently creating the benzene-rings needed by cancer drugs in the vicinity of cancer cells. By using non-toxic substances, and only joining them together to form active anticancer drugs at the tumor site, they saw a 1000-times increase in the cancer-inhibiting activity of the drugs. Simply administering the ingredients needed for the drug, along with the transition-metal catalyst, through a vein, cancer growth was inhibited without side effects such as weight loss.
This is the first time that active anticancer drugs have been assembled on-site and effectively combatted cancer by simply injecting the ingredients for the drug through a vein. In addition to benzene, the methodology developed in this study is expected to enable a variety of other molecules to be synthesized inside the body. The hope is that this type of chemotherapy will become a useful therapeutic platform for the future of cancer treatment.
“Many patients with cancer are dying because of the side effects of treatment. We believe our technology, which attacks cancer cells highly effectively without side effects, will be able to save lives,” says Tanaka. “The method will also allow us to reconsider using compounds that have not been used before because they were too toxic when delivered to the whole body. Now they can be synthesized at the tumor site without affecting healthy tissue. We believe this is a paradigm shift for pharmaceuticals and drug discovery.”
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