Publisher Health

More than two years after the COVID-19 pandemic erupted, scientists have become increasingly aware of a group of patients — so-called ‘long haulers’ — who remain plagued by a combination of symptoms long after the infection passes. In a study published in the Journal of Clinical Neuroscience, specialists from Massachusetts General Hospital (MGH) describe their findings related to their multidisciplinary clinical work in this area.
Commonly, patients with long COVID present with ‘brain fog’, a vague description including lack of sleep, anxiety, depression and a history of headache or migraine combined with trouble with attention and word finding difficulties as well as executive dysfunction,” says Zeina Chemali, MD, MPH, director, Neuropsychiatry Clinics and Training at MGH, and medical director of the McCance Center for Brain Health . “In the patients we treated with long COVID who presented with “brain fog” we found that the root cause of this commonly used term is often multifactorial.”
In their study conducted over 15 months from February 2020-May 2021, Chemali and colleagues followed 87 confirmed and 13 presumed cases of non-hospitalized individuals with lasting symptoms beyond six months after COVID-19 infection.
A key feature of the study is that most (75%) of the cohort were white educated women. “Even though we know Black Americans and Latinx individuals got very sick with COVID-19, we did not see them in the long haulers clinic,” notes Chemali who emphasizes this finding likely follows from disparity in healthcare with inability to find time and access to the care needed.
The post-COVID-19 long haulers clinic quickly became the launching base to advance the NIH-funded RECOVER study with principal investigator Ingrid Bassett, MD, investigator in the hospital’s Division of Infectious Diseases. The study is aims to understand how and why COVID-19 affects people differently. “The most important question is what is it in a person’s make-up that influences how they react to COVID-19 in a specific way and exhibit certain symptoms?” Chemali asks. “Why do some people get very sick, others do not, some become long haulers and why do some people never get COVID-19 at all?” To date, approximately 200 patients have been referred from the MGH COVID-19 long haulers clinic to the RECOVER Study and other trials conducted at throughout the Mass General Brigham healthcare system.
“Everyone is still grappling with understanding long COVID,” concludes Chemali, noting that similar symptoms are found in patients with other post-viral diseases, post-traumatic brain injury, concussive syndrome or the vaguely understood chronic fatigue syndrome. “From a neurocircuitry point of view, we see that frontal networks are the most vulnerable in the post-COVID-19 phase.”
Chemali suggests that addressing ways to restore frontal neurocircuitry — such as good quality sleep, alleviating pain and headaches, treating anxiety and depression, and targeting attention and executive functions — as well as offering support and promoting self-care are the pillars of a good and sustainable recovery.
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UBC researchers demonstrated in 2019 that pre-schoolers can safely overcome peanut allergies with a treatment called oral immunotherapy.
Now they have evidence that the earlier pre-schoolers start this treatment, the better.
This real-world study focused on infants younger than 12 months old and reveals that not only is oral immunotherapy effective against peanut allergies, it’s even safer for this age group than it is for toddlers and older pre-schoolers.
“This treatment is affordable, very safe and highly effective, particularly if we can get the treatment going before the infant is 12 months old,” said Dr. Edmond Chan, the study’s senior author who is also a clinical professor and head of allergy and immunology in UBC’s department of pediatrics at the BC Children’s Hospital Research Institute.
The study, recently published in the Journal of Allergy and Clinical Immunology: In Practice, looked specifically at outcomes for a group of 69 infants among a larger study group of 452 children aged five and under.
Oral immunotherapy is a treatment protocol in which a patient consumes small amounts of the allergenic food — in this case, peanut flour — with the dose gradually increased to a determined maximum amount. The aim is to desensitize the child until they can have a full serving of peanut protein without triggering a dangerous reaction. To sustain their immunity, the child must continue to eat peanut products on a regular basis long term.

A common hormone disorder among women of reproductive age has been linked to an increased risk of adverse cardiovascular events and pregnancy outcomes at the time of birth, according to a new study led by Johns Hopkins Medicine researchers.
The study was published June 16 in the Journal of the American Heart Association.
Polycystic ovary syndrome (PCOS) affects an estimated 5%-13% of women in the general population. It causes irregular periods, excess levels of male hormones (androgens) and, at times, infertility. Building on previous research that shows PCOS is linked to future cardiovascular disease risks later in life, the new findings reveal that it can also significantly increase heart problems among pregnant women during delivery. These problems include preeclampsia (dangerous levels of high blood pressure with organ damage), peripartum cardiomyopathy (a weak or enlarged heart), heart failure, abnormal heart rhythms and venous thromboembolism (blood clots), compared with women without PCOS.
“Oftentimes, women with PCOS are understandably concerned about the immediate effects, like an irregular menstrual cycle, excess body hair, weight gain and acne. However, the long-term cardiovascular complications are also a serious problem,” said Erin Michos, M.D., associate professor of medicine at the Johns Hopkins University School of Medicine and corresponding author of the study. Michos said the new study should encourage women with PCOS to live a heart-healthy lifestyle before, during and after pregnancy to reduce the risk of adverse outcomes.
For the study, researchers analyzed data gathered on more than 17 million U.S. births between 2002 and 2019 drawn from the National Inpatient Sample. Among those with hospitalized deliveries, 195,675 had PCOS. The prevalence of PCOS — and obesity among those with the hormone disorder — increased significantly during the study period. The number of women with PCOS went from a reported 569 per 100,000 deliveries in 2002 to 15,349 per 100,000 deliveries in 2019. During that same time period, obesity also skyrocketed from 5.7% to 28.2% among women with PCOS. Michos and colleagues note that some of the increase in PCOS may be due to better detection and diagnosis.
After adjusting for age, race, other disorders not related to PCOS, insurance coverage and income, PCOS remained an independent predictor of heart complications during delivery compared with women who did not have the hormone disorder. Complications included preeclampsia, with a 56% increased comparative risk; heart failure, with a 76% increased risk; abnormal heart rhythms, with a two-fold higher risk; weakened heart, with a 79% higher risk; and an 82% higher risk of developing blood clots.

The world’s first study of the impact of childhood fitness and obesity on cognition in middle age, followed over 1200 people who were children in 1985 for over 30 years, has found that better performance on physical tests is related to better cognition later in life and may protect against dementia in later years.
Importantly these findings are not impacted by academic ability and socioeconomic status at childhood, or by smoking and alcohol consumption at midlife.
Led by Dr Jamie Tait and Associate Professor Michele Callisaya from the National Centre for Healthy Ageing, based at Peninsula Health and Monash University in Melbourne, along with investigators from the Childhood Determinants of Adult Health study from the Menzies Institute for Medical Research at the University of Tasmania, the landmark study is published today (TBC) in the Journal of Science and Medicine in Sport.
It is known that children who develop muscular strength, cardiorespiratory fitness and endurance due to sport and activity have better health outcomes later in life. Higher adult fitness is also associated with better cognition and reduced risk of dementia later in life.
Following over 1200 people from 1985 when they were between 7 and 15 years old all the way to 2017-19, this is the first significant study to look for links between objectively measured fitness and obesity in childhood with cognition in middle age, with the idea that early activity levels, fitness and metabolic health may protect against dementia in our older years.
In 1985, 1244 participants aged 7-15 years from the Australian Childhood Determinants of Adult Health study were assessed for fitness (cardiorespiratory, muscular power, muscular endurance) and anthropometry (waist-to-hip ratio).

Scientists have identified the biochemical signals that control the emergence of the body pattern in the primate embryo. This will guide work to understand birth defects and pregnancy loss in humans.
The study also provides a crucial reference for foetal tissue generation in the lab — such tissue is in short supply but is needed for drug screening and studies into stem cell-based treatments to regenerate body tissues in diseases like Parkinson’s, for example.
Embryos develop from a clump of cells into highly organised structures. However, until now the signals orchestrating this transformation have remained hidden from observation inside the womb.
Measuring gene activity in three dimensions, researchers have generated molecular maps of the second week of gestation as it has never been seen before. Their work is published today in the journal Nature.
“This work will provide a definitive laboratory reference for future studies of early embryo development, and the embryonic origins of disease,” said Dr Thorsten Boroviak in the University of Cambridge’s Department of Physiology, Development and Neuroscience and senior author of the study.
The second week of gestation is one of the most mysterious, yet critical, stages of embryo development. Failure of development during this time is one of the major causes of early pregnancy loss and birth defects.

The cerebellum is essential for sensorimotor control but also contributes to higher cognitive functions including social behaviors. In a recent study, an international research consortium including scientists from Inserm — University of Montpellier (France), the Institut de Neurociències Universitat Autònoma de Barcelona (INc-UAB) (Spain), and the University of Lausanne (Switzerland) uncovered how dopamine in the cerebellum modulates social behaviors via its action on D2 receptors (D2R). By using different mouse models and genetic tools, the researchers’ work shows that changes in D2R levels in a specific cerebellar cell type, the Purkinje cells, alter sociability and preference for social novelty without affecting motor functions. These new findings pave the way to determine whether socially related psychiatric disorders, such as autism spectrum disorders (ASD), bipolar mood disorder, or schizophrenia, are also associated with altered dopamine receptors expression in specific cerebellar cell types.
Dopamine (DA) neurons are a major component of the brain reward system. By encoding motivational value and salience, they tighly regulate motivation, emotional states and social interactions. Although the regulation of these processes has been largely ascribed to neural circuits embedded in limbic regions, recent evidence indicate that the cerebellum, a region primarily involved in motor control, may also contribute to higher cognitive functions including social behaviors. However, whether cerebellar dopamine signaling could participate to the modulation of these functions remained unexplored. Researchers from Inserm — Montpellier University (France), the Institut de Neurociències UAB (Spain), and the University of Lausanne (Switzerland) uncovered a new role for dopamine as modulator of social behaviors in the mouse cerebellum.
By combining cell type-specific transcriptomics, immunofluorescence analyses and 3D imaging, researchers first demonstrated the presence of dopamine D2 receptors (D2R) in Purkinje cells (PCs), the output neurons of the cerebellar cortex. Using patch-clamp recordings, they were able show D2R modulated synaptic excitation onto PCs. “This first set of results was already determinant for us, as they unveiled that D2R were present in the cerebellum and that, despite their low expression level, they were functional,” highlights Dr Emmanuel Valjent, research director at Inserm (France), and coordinator of the study.
The researchers then went on to study their functions. By using genetic approaches to invalidate or overexpress D2R selectively in PCs, they analyzed the impact of these alterations on motor and non-motor cerebellar functions. “We have uncovered an unexpected causal link between PCs D2R expression levels right in the center of the cerebellum, the Crus I/II lobules, and the modulation of social behaviors. Reducing the expression of this specific dopamine receptor impaired the sociability of mice as well as their preference for social novelty, while their coordination and motor functions remained unaffected” explains Dr. Laura Cutando, Marie-Curie researcher at the Mitochondrial Neuropathology research group at INc-UAB, and first author of the article.
This study constitutes a first step towards a better understanding of the role of dopamine in the cerebellum and the mechanisms underlying psychiatric disorders such as schizophrenia, ADHD and anxiety disorders, which have all in common aberrant DA signaing and altered social behaviors.
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During recent decades, the rate of infertility among women in the United States has remained largely the same, according to researchers at Johns Hopkins Medicine. Their new analysis of data collected from 1995 and 2019, and published June 14 in the journal Fertility and Sterility, found that infertility is more common among women who are older, who are non-Hispanic Black and who have less income or education, and women without access to sexual and reproductive health services.
“These findings suggest we have to continue to invest in our public health services and push for equal access to reproductive and sexual health care if we want to meet national goals of reducing infertility,” says Johns Hopkins University School of Medicine medical student Morgan Snow, who is the study’s first author.
Infertility — defined as the inability to achieve a pregnancy after at least a year of unprotected sex — affects millions of men and women of reproductive age. Studies conducted in the early 2000s found that rates of infertility declined throughout the 1980s and 1990s, although reasons for the decline were unclear.
More recently, experts suspect that rates of sexually transmitted infections, which have consistently risen from year to year, are contributing to the rise in the infertility rate. In addition, they say, the number of women receiving preventive gynecologic care has dropped and the average age of first-time mothers has risen.
“This is a unique time period where sexually transmitted infections are on the rise and there are a number of emerging threats to health care access,” says Maria Trent, M.D., M.P.H., Bloomberg Professor of American Health and Pediatrics at the Johns Hopkins University schools of public health and medicine, and senior author of the research report. “For care providers who are working with women, it’s important to understand how these factors might be influencing fertility.”
For the new study, Snow and Trent analyzed data on 53,764 women who participated in the federally supported National Survey of Family Growth (NSFG). While the survey did not ask explicitly about infertility, it contained questions about sexual activity, contraception and pregnancy that were not used in previous studies to estimate infertility rates. It also collected information about sociodemographic and health care factors.
Based on the responses, the researchers concluded that the rate of infertility varied slightly from year to year, with a low from 2006 to 2010 of 5.8% and a high between 2017 to 2019 of 8.1%. However, these fluctuations are not considered statistically significant, and the team concluded that overall fertility rates did not significantly change during the study period.
In particular populations, however, infertility rates were significantly higher than average, compared with the general population. Women age 40 to 44 were about 11 times more likely to be infertile than younger women, women who did not complete high school were twice as likely to be infertile as those with higher levels of education, non-Hispanic Black women were 44% more likely to be infertile than women of other races and women who had not recently received sexual health care were 61% more likely to be infertile. Unlike previous studies, the new data did not show a higher rate of infertility for Hispanic women.
“These numbers tell us that fertility is still a problem, particularly for certain vulnerable populations,” says Trent, who is also the director of the Division of Adolescent/Young Adult Medicine at Johns Hopkins Children’s Center.
Understanding who is at highest risk of infertility can help shape public health guidelines and messaging, Trent notes. The association between preventive health care access and infertility, for example, suggests that emphasis on identifying and treating sexually transmitted infections may reduce infertility by reducing rates of pelvic inflammatory disease, which is a major risk factor for infertility.
The researchers caution that their study was limited by its reliance on questions included in the NSFG, which were not designed to directly measure infertility rates or access to care. However, the study offers a valuable comparison with previous studies on infertility rates, Snow says. More work is needed to understand the complex sociodemographic factors behind the associations.
In addition to Snow and Trent, authors of the Fertility and Sterility paper are Jamie Perin, Ph.D., of The Johns Hopkins University, and Tyler Vranich, M.S., a former Johns Hopkins University student who is now a student at the Medical University of South Carolina. The research was supported by the National Institute of Nursing Research (NINR-R01NR013507 — Trent).

Severe storms flooded parts of the facility in Sturgis, Mich., which went offline in February over contamination concerns, exacerbating a nationwide formula shortage.Abbott Nutrition, which worsened a baby formula shortage in the United States when it temporarily shut down a Michigan plant in February because of the presence of bacteria, said it had again stopped production at the plant, this time because of flooding during a severe storm.The company said on Wednesday that it was forced to stop production of its EleCare specialty formula in Sturgis, Mich., one of Abbott’s five manufacturing sites, after severe weather moved through southwestern Michigan on Monday, flooding parts of the plant.The company said that it was assessing damage and cleaning the plant, which would delay production and distribution for a few weeks, but that it had sufficient supplies of EleCare and most of its specialty and metabolic formulas to meet demand until new formula is available.“These products are being released to consumers in need in coordination with health care professionals,” it said.Robert M. Califf, the commissioner of the Food and Drug Administration, said that the agency had been informed about the stoppage but that it was not expected to have much impact, given increased imports of formula as well as production by Abbott and other manufacturers.Read More on the Baby Formula ShortageUnderstand the Shortage: With just a handful of companies making infant formula for the U.S. market, the shutdown of an Abbott Laboratories plant had an outsize effect.Premature Babies: Many newborns who spend time in the NICU rely on specialized formula to thrive once they come home. As the shortage continues, their parents can’t find it anywhere.Pumping for the Cause: In New York City, the shortage has prompted a huge volunteer effort, with some mothers donating their excess supply of breast milk to help other parents.An Emotional Toll: The shortage is forcing many new mothers to push themselves harder to breastfeed, with some even looking for ways to start again after having stopped.“While this is an unfortunate setback and a reminder that natural weather events can also cause unforeseen supply chain disruptions, I want to reassure consumers the all-of-government work to increase supply means we’ll have more than enough product to meet current demand,” he said in a statement on Twitter.The storm disrupted power and caused wind damage, the Sturgis Journal reported, and the city’s municipal airport recorded 1.5 inches of rain.The stoppage at the plant was the latest twist in the baby formula shortage in the United States, which started earlier this year, when pandemic-related supply chain issues, including a scarcity of some ingredients, made it difficult for parents to find formula.In February, the problems were exacerbated when Abbott recalled batches of its Similac, Alimentum and EleCare formulas and shut down the Sturgis facility after the F.D.A. received four consumer complaints of bacterial infections related to the formulas. Three of the complaints concerned Cronobacter sakazakii, a bacterium that can cause severe, life-threatening infections or inflammation of the membranes that protect the brain and spine.At least two babies died, although Abbott has said that there was no evidence its formula caused any known infant illnesses.After the shutdown, Abbott said it increased production at other manufacturing plants in the United States and at one in Ireland.Navigating the Baby Formula Shortage in the U.S.Card 1 of 6A growing problem.

A new study shows targeting a protein in smooth muscle cells can block and decrease buildup of atherosclerotic plaque in mouse models, according to researchers with UTHealth Houston.
The study was published today in Arteriosclerosis, Thrombosis, and Vascular Biology.
Atherosclerosis is a common condition that develops when plaque builds up inside the arteries. Diseases linked to atherosclerosis, such as coronary artery disease, are the leading cause of death in the United States, and nearly half of Americans with the condition don’t know they have it. Atherosclerosis can affect most of the arteries in the body, including arteries in the heart, brain, arms, legs, pelvis, and kidneys.
“We are trying to identify new pathways that cause atherosclerotic plaque buildup, in particular pathways that involve a certain cell type, called smooth muscle cells,” said Dianna Milewicz, MD, PhD, lead author of the study and professor and President George Bush Chair in Cardiovascular Medicine at McGovern Medical School at UTHealth Houston. “For many years, researchers have been focused on other cell types, like endothelial cells and macrophages, but more recent studies have highlighted a role of smooth muscle cells in plaque formation. We found that if we block a specific protein in smooth muscle cells, we can effectively block the majority of plaque formation from occurring in an animal model.”
Using a knockout method, researchers fed genetically modified mice a high fat diet and caused the mice to have high cholesterol levels in their blood to drive atherosclerotic plaque formation. Blocking a specific protein called PERK in these mice resulted in an 80% decrease of atherosclerotic plaque buildup in male mice.
“Males tend to have more of this buildup than females. This tells us that blocking PERK in smooth muscle cells is important in plaque formation. Interestingly, this protein is activated in smooth muscle cells by too much cholesterol in the cells,” Milewicz said.
Current treatments to help patients who suffer from atherosclerosis-related conditions include lifestyle and diet changes, medications such as statins and PCSK9 inhibitors, and in more severe cases, procedures to open blocked arteries. However, Milewicz says lifestyle changes may not always help, and current medications have side effects or can be prohibitively expensive.
Researchers are hopeful these findings can translate to clinical care.
“There are a lot of drugs on the market that block the smooth muscle cell pathway,” said Abhijnan Chattopadhyay, PhD, first author on the study and a research fellow in the Division of Medical Genetics at McGovern Medical School. “Now that we know this buildup can be blocked by targeting smooth muscle cells, we can use medication that is already available and target this pathway to help patients with atherosclerotic plaque buildup. This is just another way we can block or lower the plaque buildup, especially for those who are unable to prevent atherosclerosis with lifestyle modifications or statins.”
Additional McGovern Medical School authors include Suravi Majumder, PhD; Kaveeta Kaw, BS; Zhen Zhou, MD; Siddharth K. Prakash, MD, PhD; Anita Kaw, BA; Maximillian Buja, MD; Callie S. Kwartler, PhD, and Pujun Guan, MM, with McGovern Medical School and The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences. Chen Zhang, MD, with Baylor College of Medicine and Texas Heart Institute, also contributed to the study.

Researchers have developed a unique 3D printed system for harvesting stem cells from bioreactors, offering the potential for high quality, wide-scale production of stem cells in Australia at a lower cost.
Stem cells offer great promise in the treatment of many diseases and injuries, from arthritis and diabetes to cancer, due to their ability to replace damaged cells. However, current technology used to harvest stem cells is labour intensive, time consuming and expensive.
Biomedical engineer Professor Majid Warkiani from the University of Technology Sydney led the translational research, in collaboration with industry partner Regeneus — an Australian biotechnology company developing stem cell therapies to treat inflammatory conditions and pain.
“Our cutting-edge technology, which uses 3D printing and microfluidics to integrate a number of production steps into one device can help make stem cell therapies more widely available to patients at a lower cost,” said Professor Warkiani.
“While this world-first system is currently at the prototype stage, we are working closely with biotechnology companies to commercialise the technology. Importantly, it is a closed system with no human intervention, which is necessary for current good manufacturing practices,” he said.
Microfluidics is the precise control of fluid at microscopic levels, which can be used to manipulate cells and particles. Advances in 3D printing have allowed for the direct construction of microfluidic equipment, and thus rapid prototyping and building of integrated systems.
The new system was developed to process mesenchymal stem cells, a type of adult stem cell that can divide and differentiate into multiple tissue cells including bone, cartilage, muscle, fat, and connective tissue.
Mesenchymal stem cells are initially extracted from human bone marrow, fat tissue or blood. They are then transferred to a bioreactor in the lab and combined with microcarriers to allow the cells to proliferate.
The new system combines four micromixers, one spiral microfluidic separator and one microfluidic concentrator to detach and separate the mesenchymal stem cells from microcarriers and concentrate them for downstream processing.
Professor Warkiani said other bioprocessing industrial challenges can also be addressed using the same technology and workflow, helping to reduce costs and increase the quality of a range of life-saving products including stem cells and CAR-T cells.
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