Publisher Health

Researchers have found that receiving a COVID-19 vaccine during pregnancy does not lead to increases in the frequency of complications around the time of childbirth. The findings, which are published in JAMA, provide further assurances about the safety of mRNA vaccines for this particularly unique population.
Lead author Dr. Deshayne Fell led the study of nearly 100,000 pregnancies by analyzing data from BORN Ontario (Ontario’s provincial birth registry), which is linked to the province’s COVID-19 immunization database.
While analyzing childbirths between December 2020 and September 2021, Dr. Fell found: Approximately 23 percent (over 22,000 individuals) received at least one dose of a COVID-19 vaccine during pregnancy. No increase in the babies’ need for neonatal intensive care unit (NICU) admission. No frequency of low Apgar scores (an assessment at birth that can identify babies who may need special care, such as extra help with their breathing) in babies born to vaccinated mothers, compared to babies born to unvaccinated mothers. Vaccination was not associated with increased risk of: heavy bleeding after childbirth; infection in the uterus or membrane; emergency caesarean section among the vaccinated mothers, compared to unvaccinated mothers. “There is increasing evidence from studies around the world showing that COVID-19 vaccination during pregnancy is not associated with poor pregnancy or birth outcomes, and showing that COVID-19 vaccines are effective at preventing COVID-19 in pregnant mothers and also in their babies in the first few months of life.” says Dr. Fell, an Associate Professor in the University of Ottawa’s Faculty of Medicine and a Scientist at the CHEO Research Institute.
Vaccination against COVID-19 is recommended for pregnant individuals since they are at a higher risk of complications from the disease, including hospitalization, ICU admission and death, compared with nonpregnant individuals. COVID-19 during pregnancy has also been linked with increased risks of pregnancy complications such as preterm birth of the babies.
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Materials provided by University of Ottawa. Original written by Paul Logothetis. Note: Content may be edited for style and length.

One of the essential roles of the forensic anthropologist is the development of a biological profile from a skeleton, which includes the estimation of assigned sex, age, stature and possibly ancestry or population affinity (skeletal characteristics associated with groups of people). Until recently, ancestry was considered an essential component of the biological profile by most U.S.-based practicing forensic anthropologists, however, some methods are poorly understood and may inadvertently perpetuate the long-debunked biological race concept and impede identification efforts, especially for people of color.
To address the problematic nature of ancestry-dependent estimation methods, researchers from Boston University School of Medicine (BUSM) have proposed a method of assigned sex estimation that is “population-inclusive,” or one that did not inherently rely on any estimation of ancestry (population affinity) by using 3D volume-rendered computed tomography (CT) scans of ancestry skulls to estimate assigned sex at birth.
Assigned sex or “sex at birth” refers to an individual’s assigned classification at birth by medical professionals, usually male or female and is determined mostly by external anatomy, in addition to chromosomes, hormones, secondary sex characteristics and internal/external reproductive organs. For skeletonized remains, estimating the assigned sex is possible through the skeleton itself, which is a secondary sex characteristic, and is reflective of primary sex characteristics (soft tissue).
“This study seeks to engage with the ongoing conversation regarding the role of ancestry in the biological profile by proposing a method of assigned sex estimation from computed tomography (CT) scans that does not rely on an estimation of population affinity,” explains corresponding author Sean Tallman, PhD, RPA, assistant professor of anatomy and neurobiology at BUSM.
Study data was collected using the New Mexico Descendent Image Database, which contains CT scans from over 15,000 decedents with full-body scout images. Various metric measurements of the skull were collected using a 3D measuring tool between 18 standard points of measurement of the cranium and mandible (largest bone in the skull). Relatedly, five nonmetric (shape) traits were also analyzed. The metric and nonmetric data were statistically analyzed and showed that population-inclusive models performed statistically similar to the population-specific models, indicating that a population-inclusive model can be applied in place of population specific models, without deterring the estimation of assigned sex.
“A population-inclusive model is applicable in cases where population affinity is unknown, intentionally not estimated in order to mitigate potential for racial biases like the ‘missing white woman syndrome’, and in light of the debate surrounding the removal of certain ancestry estimation methods from the construction of the biological profile,” said Tallman.
According to the researchers, a population-inclusive model can be used to accurately estimate assigned sex, without producing significantly different or statistically lower classification rates. “Furthermore, estimation of assigned sex and other biological profile parameters from 3D-VR CT images of the skull can be used to further the study of human skeletal variation and can be a tool for reconstructing outdated ancestry-based estimation methods,” adds Tallman.
These findings appear online in the journal Forensic Sciences.
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Bacteria, fungi, and yeast are very good at excreting useful substances such as weak acids. One way in which they do this is through passive diffusion of molecules across the cell membrane. At the same time, cells need to prevent leakage of numerous small molecules. Yeast cells, for instance, can live in hostile environments thanks to a very robust and relatively impermeable membrane system. Biochemists at the University of Groningen, the Netherlands, have studied how the composition of the membrane affects passive diffusion and the robustness of the cell membrane. Their results, which were published in Nature Communications 25 March, could help the biotech industry to optimize microbial production of useful molecules and help in drug design.
Border control is very important to cells. Their membranes separate the inner and outer environments, which are quite different. To absorb useful compounds, such as nutrients, or to excrete waste, cells can use selective transport systems. However, some transport across the membrane takes place by passive diffusion. This is a non-selective process that will let some molecules go in or out, depending on their size and hydrophobicity, for example. Active transporters have been studied extensively; however, our knowledge of passive diffusion through the membrane is still very incomplete.
Synthetic vesicles
This is a problem for the biotechnology industry, which uses cells as factories to produce a myriad of useful substances and that needs these worker cells to survive under harsh conditions, for example in an environment with high alcohol or weak acid concentrations. Bert Poolman, Professor of Biochemistry at the University of Groningen, was approached by a biotech company that was interested in producing lactic acid in bacteria. They wanted to know more about passive diffusion. This fitted in nicely with another project that Poolman is working on. ‘We are highly interested in these passive transport processes because of our involvement in a project to build a synthetic cell,’ says Poolman. ‘If you can use passive diffusion instead of an active transport system, you need fewer parts to construct such a cell.’
So, he combined both questions in a research project. ‘We started out with a systematic study of what causes the differences in permeability of yeast membranes and bacterial membranes,’ says Poolman. His team created synthetic vesicles that were made up of three to four different lipids. Ergosterol or cholesterol was added to the membranes to affect their fluidity and rigidity. A range of small molecules was tested using this system and the results from these experiments guided molecular dynamic simulations of diffusion through membranes. The in-silico studies, supervised by Professor Siewert-Jan Marrink, provided a deeper insight into the molecular mechanism of diffusion.
Tweaking
The fatty acid tails of the lipids turned out to be most important in determining the properties of membranes, whereas the hydrophilic head groups had little effect on the permeability. The length of the tails also mattered. ‘And saturated tails, with no double carbon bonds, are stiffer than unsaturated ones. Hydrophobic interactions cause a close packing of these tails, resulting in a gel phase that is not very penetrable,’ explains Poolman. Sterols increase the fluidity but in the case of yeast, which uses ergosterol, the permeability remains low. ‘Thus, by tweaking the saturation of the fatty acids and the type and amount of sterol in the membrane, we can modify the permeability of the plasma membrane of yeast and bacterial cells.’
Poolman and his colleagues have, therefore, defined a number of variables that alter the permeability of membranes for different classes of compounds. This information can be used by companies that use yeasts or bacteria as cell factories. ‘However, our results cannot be directly applied to those cells,’ warns Poolman. ‘Real membranes contain hundreds of different lipids and the composition can vary between different locations in the membrane. In addition, these cell membranes contain all kinds of proteins. If you make changes in, for example, the lipid composition of the membrane, a lot can go wrong and the function of a membrane protein can be affected.’
Drug design
The increased understanding of the physical processes that affect permeability can help companies to understand why certain cells are better for specific processes than others. ‘The usual way to tweak strains is by directed evolution. Our results will help companies to better understand the results of those optimizations and guide their cell engineering efforts.’
Another application is the design of drugs that act inside cells. ‘Pharmaceutical companies use a set of empirically established rules to optimize drugs for action inside cells, based on parameters such as size or polarity. Our study highlights the importance of the membrane composition of the targeted cells and this could help in drug design.’
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The rate at which older adults were treated for substance abuse increased sharply from 2000 to 2017, UConn Health researchers report in the March 28 issue of the Journal of Clinical Psychiatry. The rates of older adults getting treatment increased substantially while the rate of younger adults remained stable over time.
The Baby Boom generation born from 1946 to 1964 has had consistently high rates of substance use. As members of this generation enter older adulthood, the numbers of older adults seeking treatment for substance abuse has also increased. According to data from the Treatment Episode Dataset, a nationwide compilation of services used, available from the Substance Abuse and Mental Health Services Administration (SAMHSA), the rate of people aged 55 or over getting treatment for substance use increased from 8.8 per 1,000 people in 2000 to 15.1 per 1,000 people in 2017. The increase was almost entirely due to treatment for cannabis and cocaine use; alcohol-related treatment rates stayed about the same over time.
Although the data does not include information that would explain the increase, the researchers have hypotheses. The first is that the Baby Boomers began transitioning to older adulthood from 2001-2017, and their higher rates of substance use followed them.
The researchers also suspect that currently there is less stigma attached to substance abuse than there was in the past, and so people, including older adults, are more likely to seek help. This theory is buttressed by SAMHSA data showing that the increase in substance treatment was mostly due to self-referrals, not forced referrals from the criminal justice system.
“I am primarily interested in whether people are getting the correct care for substance abuse. I also have a special interest in gerontology,” says T. Greg Rhee, a UConn School of Medicine psychiatric epidemiologist and the senior author of the study. From Rhee’s point of view, the SAMHSA data aren’t necessarily bad. Self-referrals mean older adults are recognizing when they need help.
“The population of older adults in the US is growing, and so is the number who use cocaine and cannabis. We really need to think about how to best address this,” Rhee says.
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Materials provided by University of Connecticut. Original written by Kim Krieger. Note: Content may be edited for style and length.

A Columbia Engineering team has developed a technology that could replace conventional biopsies and histology with real-time imaging within the living body. Described in a new paper published today in Nature Biomedical Engineering, MediSCAPE is a high-speed 3D microscope capable of capturing images of tissue structures that could guide surgeons to navigate tumors and their boundaries without needing to remove tissues and wait for pathology results.
For many medical procedures, particularly cancer surgery and screening, it is common for doctors to take a biopsy, cutting out small pieces of tissue to be able to take a closer look at them with a microscope. “The way that biopsy samples are processed hasn’t changed in 100 years, they are cut out, fixed, embedded, sliced, stained with dyes, positioned on a glass slide, and viewed by a pathologist using a simple microscope. This is why it can take days to hear news back about your diagnosis after a biopsy,” says Elizabeth Hillman, professor of biomedical engineering and radiology at Columbia University and senior author of the study.
Hillman’s group dreamed of a bold alternative, wondering whether they could capture images of the tissue while it is still within the body. “Such a technology could give a doctor real-time feedback about what type of tissue they are looking at without the long wait,” she explains. “This instant answer would let them make informed decisions about how best to cut out a tumor and ensure there is none left behind.”
Another major benefit of the approach is that cutting tissue out, just to figure out what it is, is a hard decision for doctors, especially for precious tissues such as the brain, spinal cord, nerves, the eye, and areas of the face. This means that doctors can miss important areas of disease. “Because we can image the living tissue, without cutting it out, we hope that MediSCAPE will make those decisions a thing of the past,” says Hillman.
Although some microscopes for surgical guidance are already available, they only give doctors an image of a small, single 2D plane, making it difficult to quickly survey larger areas of tissue and interpret results. These microscopes also generally require a fluorescent dye to be injected into the patient, which takes time and can limit their use for certain patients.
Over the past decade, Hillman, who is also Herbert and Florence Irving Professor at Columbia’s Zuckerman Mind Brain Behavior Institute, has been developing new kinds of microscopes for neuroscience research that can capture very fast 3D images of living samples like tiny worms, fish, and flies to see how neurons throughout their brains and bodies fire when they move. The team decided to test whether their technology, termed SCAPE (for Swept Confocally Aligned Planar Excitation microscopy) could see anything useful in tissues from other parts of the body.

Headaches such as migraine are among the leading causes of morbidity worldwide, but most treatments provide only partial relief. While scientists know that migraine and related headaches are caused by activity in a part of the nervous system known as the trigeminal ganglion (TG), it remains unclear which genes and cell types of the TG are involved. By analyzing both human and mouse TG, investigators from Brigham and Women’s Hospital and Massachusetts General Hospital profiled, at single-cell resolution, the genes expressed in each TG cell type. Their research, published in Neuron, will allow researchers to design more effective treatments for pain by selectively targeting certain genes and cells.
“Very few pain therapeutics have made it to the clinic, despite strong efficacy in animal models, so our goal was to analyze human tissue to look for new targets for headache and facial pain treatment,” said William Renthal, MD, PhD, of the Department of Neurology at the Brigham. “We now have an atlas of the genes that are expressed in each of the cell types in the TG, the key relay center for migraine and facial pain, and we are now using this tool to identify potential therapeutic targets that are selectively expressed in cell types that drive head pain. We believe this will lead to more precise medicines without as many side effects.”
In addition to analyzing the TG of four human donors, the researchers studied two mouse models of headache. Importantly, they found that while cell types between mice and human are largely conserved, some of the genes known to be involved in pain are expressed in different subsets of cells in mice versus humans. This gave the researchers new ideas about which cells to study further.
“A major value of this study is that it wasn’t limited to one specific cell-type or branch of the trigeminal ganglion,” said Jochen K. Lennerz, MD, PhD, of the Center for Integrated Diagnostics in the Department of Pathology at MGH. Lennerz’s lab performed the complex tissue-harvesting procedures required to extract the TG, which is located inside the cranium but has neurons that enervate the teeth, eyes, and other facial structures. “We included all of the cells that make up the TG,” he said. “This was a very holistic approach which has resulted in an amazing compendium that researchers can look at from all perspectives and specialties. It may not only be neurons we are looking for when identifying biomolecules as therapeutic targets.”
The information from the researchers’ atlas, which is available publicly online, could prompt new investigations into the molecular basis of different varieties of pain, such as tooth pain. It may also shed light on how to treat head pain beyond migraine, including post-concussive headaches or cluster headaches.
Going forward, the researchers plan to improve the current atlas by sequencing additional human tissues. They hope that the atlas can help researchers develop more selective pain therapeutics by targeting, through gene therapies, the specific cells they’ve identified.
“We have a resource now that allows an individual to go online, look up a gene of interest, find out where it’s expressed and how it’s regulated, and then use this information to inspire new experiments,” Renthal said. “This atlas is only a first draft, and we need to expand the number of donors to build a more complete one. That’s a current limitation but also a future direction for our work.”
Disclosures: Renthal receives research funding from Teva Pharmaceuticals and is on an AbbVie scientific advisory board.
Funding: Funding for this work was primarily provided by the Migraine Research Foundation and the Burroughs Wellcome Fund. Researchers are also supported by the National Institute of Neurological Disorders and Stroke (K08NS101064, R01NS119476, R01NS115972 and R01NS078263), National Institute of Drug Abuse (DP1DA054343), Teva Pharmaceuticals, Brigham and Women’s Hospital Women’s Brain Initiative and Neurotechnology studio.
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The current treatment of patients diagnosed with advanced or metastatic head and neck cancer (HNC) is ineffective. Ben-Gurion University of the Negev researchers, along with their international colleagues, have investigated and validated a potential treatment combination against the aggressive disease driven by hyper-activation of a specific signaling pathway, which is found in over 40% of HNC patients.
Their findings were just published in the Journal for ImmunoTherapy of Cancer.
Specifically, the authors showed in pre-clinical HNC models that treating tumor-bearing mice with a therapy that blocks this signaling pathway, sensitizes tumors to the immunotherapy of anti-PD1, resulting in the disappearance of tumors after the therapy combination. This effective treatment was validated in four HNC cancer models, and most mice were cured with no recurrent disease. Together with Dr. Pierre Saintygn from Lyon the authors also validated some of the findings in HNC patients.
The research was led by PhD student Manu Prasad in the laboratory of Prof. Moshe Elkabets in the Faculty of Health Sciences at Ben-Gurion University of the Negev.
“Our unique ability to generate pre-clinical HNC models and to investigate new treatment and treatment combinations provides hope for HNC patients. We sincerely hope that oncologists will test this treatment combination in HNC patients, as improving immunotherapy efficacy is crucial for prolonging the survival of cancer patients,” says Prof. Elkabets.
The authors also showed for the first time in mice bearing HNC that the treatment should be given sequentially. They found that a short treatment with trametinib is sufficient to sensitize anti-PD-1 resistant tumors. This sensitization happens because trametinib treatment, on the one hand, inhibits tumor cell proliferation and, on the other hand, down-regulates the expression of an immunosuppressive factor that determines the propagation of immunosuppressive cells in the tumor site. This effect enables cytotoxic white blood cells to reach the tumor site, and together with anti-PD1, can kill the tumor cells efficiently. However, when mice were treated with prolonged trametinib treatment, tumors failed to respond to immunotherapy.
The study was conducted by national and international groups from Soroka University Medical Center and Barzilai Medical Centers, Memorial Sloan Kettering, and Heidelberg Hospital.
This study was supported by the Cooperational Research Program of the Foundation Deutsches Krebsforschungszentrum, Heidelberg, with the Ministry of Science, Technology & Space (DKFZ-MOST #001192), the Israel Cancer Research Fund (ICRF 17-1693-RCDA), the United States — Israel Binational Science Foundation (BSF, 2017323), NSFC Israel-China project (#3409/20) and the Israel Science Foundation (ISF) Grant no. 700/16 and 302/21.
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Macrophages travel through our arteries, gobbling fat. But fat-filled macrophages can narrow blood vessels and cause heart disease. Now, UConn Health researchers describe in Nature Cardiovascular Research how deleting a protein could prevent this and potentially prevent heart attacks and strokes in humans.
Macrophages are large white blood cells that cruise through our body as a kind of clean-up crew, clearing hazardous debris. But in people with atherosclerosis — fatty deposits and inflammation in their blood vessels — macrophages can cause trouble. They eat excess fat inside artery walls, but that fat causes them to become foamy. And foamy macrophages tend to encourage inflammation in the arteries and sometimes bust apart plaques, freeing clots that can cause heart attack, stroke or embolisms elsewhere in the body.
Changing how macrophages express a certain protein could prevent that kind of bad behavior, reports a team of researchers from UConn Health. They found that the protein, called TRPM2, is activated by inflammation. It signals macrophages to start eating fat. Since inflammation of the blood vessels is one of the primary causes of atherosclerosis, TRPM2 gets activated quite a bit. All that TRPM2 activation pushes macrophage activity, which leads to more foamy macrophages and potentially more inflamed arteries. The way that TRPM2 activated macrophage activity was surprising, says Lixia Yue, a UConn School of Medicine cell biologist.
“They form a vicious cycle promoting the development of atherosclerosis,” Yue says.
Yue and Pengyu Zong, a graduate student and the first author of the paper, demonstrated one way to stop the cycle, at least in mice. They deleted TRPM2 from a type of lab mouse that tends to get atherosclerosis. Deleting that protein didn’t seem to hurt the mice, and it prevented the macrophages from getting foamy. It also alleviated the animals’ atherosclerosis.
Now Yue and Pengyu Zong, and the rest of the team are looking at whether increased TRPM2 expression in monocytes (precursors of macrophages) in the blood correlates with severity of cardiovascular disease in humans. If they find that there is a correlation, high levels of TRPM2 might be a risk marker for heart attack and stroke.
This research was funded by grants from the American Heart Association and the National Institutes of Health National Heart, Lung and Blood Institute.
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Materials provided by University of Connecticut. Original written by Kim Krieger. Note: Content may be edited for style and length.

As we age, our immune system works less well. We become more susceptible to infections and vaccinations no longer work as effectively. A research team led by Dario Riccardo Valenzano investigated whether short-lived killifish also undergo aging of the immune system. Indeed, they found that as early as four months of age, killifish have less diverse circulating antibodies compared to younger fish, which may contribute to a generalized decrease in the immune function.
The immune system must constantly respond to new attacks from pathogens and remember them in order to be protected during the next infection. For this purpose, B cells build an information repository and produce a variety of antibodies that can directly recognize the pathogens.
“We wanted to know about the antibody repertoire in old age,” explains Dario Riccardo Valenzano, who led the study. “It is difficult to study a human being’s immune system over his or her entire life, because humans live a very long time. Moreover, in humans you can only study the antibodies in peripheral blood, as it is problematic to get samples from other tissues. For this reason, we used the killifish. It is very short-lived and we can get probes from different tissues.”
Killifishes are the shortest-lived vertebrates that can be kept in the laboratory. They live for only three to four months, age in a time-lapse and have become the focus of ageing research in recent years due to these characteristics.
Less antibody diversity
The researchers were able to characterize with high accuracy all the antibodies that killifish produce. They found that older killifish have different types of antibodies in their blood than younger fish. They also had a lower diversity of antibodies throughout their bodies.
“If we have fewer different antibodies as we age, this could lead to a reduced ability to respond to infections. We now want to further investigate why the B cells lose their ability to produce diverse antibodies and whether they can possibly be rejuvenated in the killifish and thus regain this ability,” says Valenzano.
The research for this study was conducted at the Max Planck Institute for Biology of Ageing and was funded by the CECAD Cluster of Excellence for Aging Research and the Collaborative Research Center 1310 at the University of Cologne. Dario Riccardo Valenzano is now group leader of the research group “Evolutionary Biology / Microbiome-Host Interactions in Aging” at the Leibniz Institute on Aging — Fritz Lipmann Institute (FLI) and Professor at Friedrich Schiller University in Jena.
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A brain imaging study of young people at high risk of developing bipolar disorder has for the first time found evidence of weakening connections between key areas of the brain in late adolescence.
Up until now, medical researchers knew that bipolar disorder was associated with reduced communication between brain networks that are involved with emotional processing and thinking, but how these networks developed prior to the condition was a mystery.
Today in a study published in The American Journal of Psychiatry, researchers from UNSW Sydney, the Hunter Medical Research Institute (HMRI), the University of Newcastle and international institutions showed evidence of these networks diminishing over time in young adults at high genetic risk of developing bipolar disorder — which has important implications for future intervention strategies.
The researchers used diffusion-weighted magnetic imaging (dMRI) technology to scan the brains of 183 individuals over a two-year period. They examined the progressive changes in the brain scans of people with high genetic risk of developing the condition over a two year period, before comparing them with a control group of people with no risk.
People with a parent or sibling who has bipolar disorder are considered high genetic risk, and are 10 times more likely to develop the condition than people without the close family link. In the brain image scans of 97 people with high genetic risk of bipolar disorder, the researchers noted a decrease in connectivity between regions of the brain devoted to emotion processing and cognition during the two years between scans.
But in the control group of 86 people with no family history of mental illness, they observed the opposite: strengthening in the neural connections between these same regions, when the adolescent brain matures to become more adept at the cognitive and emotional reasoning required in adulthood.