Publisher Health

Fun and games could be a solution to serious problems like preeclampsia and hypertension among pregnant people and holds promise for significant progress, according to a new study from the Perelman School of Medicine at the University of Pennsylvania. Researchers found that gamification — broadly defined as the use of specially engineered games to stimulate learning and behavioral change — could generate greater levels of exercise in postpartum individuals who developed these types of conditions. In turn, the increased physical activity can help lower the risk of cardiovascular disease and death. The findings are published today in JAMA Cardiology.
“Experts have long recommended that we talk to postpartum women about adopting healthier lifestyle habits to reduce their cardiovascular risk, but there was very little guidance on how to do that,” said study first author Jennifer Lewey, MD,a cardiologist and co-director of Penn Medicine’s Pregnancy and Heart Disease Program. “The question we were trying answer was whether we could develop a digital, remote intervention to improve physical activity for high-risk postpartum women. It was a digital intervention that included gamification and what we call social incentives to improve accountability.”
Conditions like preeclampsia and gestational hypertension occur in up to 10 percent of all U.S. pregnancies and can heighten the risks of chronic hypertension and heart disease in the months and years following childbirth.
The dangers posed by these and similar conditions, known together as hypertensive disorders of pregnancy (HDP), are better understood than ever. Nevertheless, successful strategies for improving lifestyle factors like physical activity in this population have remained elusive. Gamification has been successfully used in various healthcare disciplines and beyond, but this is the first time it has been tested in women with HDPs. With that in mind, Lewey and the study’s senior author, Lisa Levine, MD, the Michael T. Mennuti, MD, associate professor in Reproductive Health and director of the Pregnancy and Heart Disease Program, set out to apply it in Maternal Fetal Medicine at Penn Medicine.
In the study, 127 participants received a wearable activity tracker to tally their daily steps. Roughly half of these individuals also took part in a game — designed by co-author Mitesh Patel, MD, an associate professor of Medicine at Penn and vice president for Clinical Transformation at Ascension — that assigned them to teams and offered points and achievement benchmarks for those who met or exceeded their step goals.
“Each postpartum woman was joined up with two other postpartum women virtually,” Lewey explained. “Each team started the week with 70 points, and every day a team member was chosen at random. If that person met her step goals for that day, the team got to keep its points. But if they didn’t, the team lost points.”
On average, game players took 647 more steps per day than those in the control group. With existing evidence showing that people who take 1,000 extra steps per day can lower their risk of developing or dying from cardiovascular disease, the finding is significant.
Making the results potentially even more impactful, about 55 percent of the study participants were Black, while about 42 percent were enrolled in Medicaid — two populations often associated with a higher likelihood of HDPs and cardiovascular risk.
“I was excited that we were able to enroll a racially diverse population,” Lewey said. “That’s important because a woman who identifies as Black or is of lower socioeconomic status has a greater burden of cardiovascular risk factors.”
While further studies will need to test the intervention over longer periods of time, the strategy could be tested now in other hospitals and health systems, Lewey said. Free or lower-cost smartphone apps can replace wearable tech, making it a relatively simple and cost-effective solution. Since many health systems keep in touch with new moms after hospital discharge, and with communication options expanding, eligible patients could be readily identified through existing channels.
“We used text messages to recruit our participants,” Lewey said. “Any health system that already uses follow-up after delivery could easily find patients for this kind of intervention. The whole idea is that being on the team and having this game structure can help keep postpartum women motivated in keeping their step count goal.”
This study was supported by the National Institutes of Health (K23HL153667, HD65987), the Institute for Translational Medicine and Therapeutics, and the National Center for Advancing Translational Science (UL1TRTOO1878).

A new study published today in the journal Genes & Development reveals a gene that normally suppresses the formation of tumours but is reprogrammed at the onset of acute promyelocytic leukemia (APL), an aggressive type of blood cancer that is responsible for 5-15% of all types of leukemia.
The findings pave the way for the development of drugs that boost the expression of the gene at the earliest stages of cancer formation, intercepting the disease before it becomes uncontrollable.
APL occurs because of chromosomal translocations, in which a chromosome breaks and a portion of it reattaches to a different chromosome. In APL, this results in a gene fusion event between the promyelocytic leukemia (PML) and retinoic acid receptor alpha (RARα) genes. Previously healthy stem cells begin to express a new protein — PML/RARα — which blocks their differentiation. Eventually, the bone marrow fills up with abnormal white blood cells known as promyelocytes that lead to a shortage of other types of blood cells and prevent normal blood production.
Treatments for APL include drugs such as all-trans-retinoic acid (ATRA), which result in 90% of cases entering remission. However, new avenues of therapy are still required for patients that do not respond to this treatment, as well as for the large proportion of patients that relapse after few years.
Despite the importance of chromosomal translocations in initiating the disease, little is known about how PML-RARα changes the genomic architecture of cells. Researchers at the Centre for Genomic Regulation (CRG) and the Centro Nacional de Análisis Genómico (CNAG-CRG) in Barcelona, and the European Institute of Oncology in Milan, used mouse models that closely mimic the progression of APL in humans to study changes in cells during the onset and progression of the disease.
They found that PML-RARα initiates a series of alterations that result in changes to the structural support of chromosomes and the repression of transcription, as well as changes in chromosomal compartments that ‘open’ or ‘close’ access to particular regions of the genome.
One of the genes most affected by these changes at an early stage was KLF4, which codes for a protein that binds to DNA to control the rate of transcription of genetic information, also known as a transcription factor. Klf4 activity was inactivated during the progression of APL. The researchers found that, when cells were manipulated to overexpress Klf4, it suppressed the self-renewal traits of cancerous cells and reversed the effects caused by the actions of PML-RARα.
“Overexpression of Klf4 acts as a tumour suppressor in acute promyelocytic leukemia. Our finding opens a new avenue of treatment to target this aggressive disease alongside existing treatments. In follow up studies, we have observed that combination of ATRA with Klf4 overexpression can suppress the cancerous traits mediated by PML-RARa, suggesting a potential therapy for non-responsive or relapsed patients that could spun off from this work,” says Glòria Mas Martin, first author of the study and previously a postdoctoral researcher at the CRG.
The method, developed in Luciano Di Croce’s laboratory at the CRG, can also be used to study changes to the genomic architecture of other types of cancer, which according to the authors, could reveal other possible therapeutic targets yet to be discovered. “The steps that initiate cancer are the most interesting because they are the equivalent of the snowball that turns into an avalanche. This approach could be used to understand the very first effects of other oncogenic proteins that act as transcriptional repressor, leading to the development of new therapies that target a mechanism before it spirals out of control,” says ICREA Research Professor Luciano Di Croce, senior author of the study and researcher at the CRG.
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According to new research from Boston Medical Center, the antibody function known as antibody dependent cellular cytotoxicity (ADCC) and the ADCC sensitivity of HIV strains may influence the transmission of HIV from mother to child during breastfeeding. These data imply that enhancing ADCC, through a vaccine, for example, may not be sufficient to prevent transmission because chronically infected individuals can harbor ADCC-resistant strains. Published in JCI Insight, the findings provide novel insights about immunologic characteristics that a vaccine may need to elicit to help block HIV transmission.
Researchers evaluated ADCC and neutralizing antibody (nAb) properties in pre-transmission plasma from HIV-1 exposed infants and from the corresponding transmitting and non-transmitting mothers’ breast milk and plasma from samples from a well-defined mother to child HIV transmission cohort. All the mothers were HIV infected, while their babies were born uninfected. Although all babies were breastfed for up to a year of life, some got HIV, while others did not.
This study shows that infants with a combination of higher pre-transmission ADCC and exposure to more ADCC susceptible strains are less likely to acquire HIV-1. This implies that efforts to eliminate transmission will need to both improve ADCC responses in at risk individuals and account for the ADCC susceptibility of the strains circulating in the infected individuals most likely to transmit the virus.
“With about 150,000 transmissions yearly, transmission of HIV from mother to child remains a significant global problem, and vaccines are needed urgently,” said Manish Sagar, an infectious diseases physician at Boston Medical Center, associate professor of medicine and microbiology at Boston University School of Medicine, and corresponding author on this study. “This study and its findings are highly relevant for developing possible new strategies to help prevent the further spread of HIV.”
Improving outcomes in the infants that become infected is important, especially due to limited access to antiretroviral therapy. Without antiretroviral treatment, the risk of transmission during the breastfeeding period is between 10 and 20 percent depending on duration of breastfeeding, which may suggest natural immune mechanisms that protect against HIV acquisition.
The results of this study provide new insights for HIV-1 vaccine efforts — in particular that, at a minimum, a possible vaccine may need to elicit antibodies that can mediate ADCC. While traditional vaccine efforts have focused on eliciting neutralizing antibodies, previous studies from Dr. Sagar’s group, along with other investigations, have found that high levels of neutralizing antibodies do not protect against HIV acquisition and that ADCC may help prevent acquisition, even in the absence of neutralizing responses. At this time, it remains unclear if ADCC can be elicited using current vaccine technologies, and it would still be insufficient in preventing HIV transmission as strategies will need to account for the ADCC sensitivity of the circulating strains in individuals likely to transmit HIV-1.
Funding for the study was supported by NIH grant R21-AI137119, K24-AI145661, P30-AI042853, and by NIH T32-5T32AI00730928.
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A little over 1% of babies born in the U.S. in 2020 fell under the category of very low birthweight, meaning they weighed less than 1,500 grams at birth or 3 pounds, 4 ounces. And considering that the Centers for Disease Control and Prevention says more than 3.5 million babies were born that year, almost 48,500 were considered to be at very low birthweight.
Many of these babies are born premature, at 30 weeks or less, and they have a high chance of having a hemorrhage in their brains shortly after birth, known as a germinal matrix hemorrhage (GMH). Bleeding like this within the substance of the brain is a form of stroke that can lead to a buildup of fluid in the brain known as hydrocephalus — both of which put babies at an increased risk of neurodevelopmental disability, and many don’t survive.
There is currently no medical treatment for GMH, and since these blood vessels are even more delicate when a baby is born prematurely, there is no way to predict or prevent bleeding in the brain after birth.
When Ramin Eskandari, M.D., a pediatric neurosurgeon at MUSC Health, read about the work that Stephen Tomlinson, Ph.D., vice chair of the Department of Microbiology and Immunology at MUSC, was conducting related to a specific part of the immune system known as the complement system, he thought it might have applications to infants as well.
“We were just having to wait for bad things to happen,” Eskandari said. “And then we had to react to them. We have no treatment for the actual hemorrhage or for preventing the stroke or hydrocephalus that comes after. Tomlinson was looking at adult pathologies in the brain, and we thought it would be a great opportunity to apply his methods to an animal model for premature infants.”
As joint principal investigators for their recent paper in the International Journal of Molecular Sciences, Tomlinson and Eskandari created a mouse model to represent premature infants of very low birthweight and to find treatment options for GMH. Mohammed Alshareef, M.D., a senior neurosurgery resident at MUSC and member of the collaborative lab, discovered that by that by inhibiting the complement system at a specific site within the brain immediately after a hemorrhage, they could prevent many of the permanent and temporary deficits that accompany hydrocephalus and stroke.

In proof-of-concept experiments, Johns Hopkins Medicine scientists say they have successfully cultivated human muscle stem cells capable of renewing themselves and repairing muscle tissue damage in mice, potentially advancing efforts to treat muscle injuries and muscle-wasting disorders in people.
A report on the experiments was published April 7 in Cell Stem Cell.
To make the self-renewing stem cells, the scientists began with laboratory-grown human skin cells that were genetically reprogrammed to a more primitive state in which the cells have the potential to become almost any type of cell in the body. At this point, the cells are known as induced pluripotent stem (IPS) cells, and they are mixed with a solution of standard cell growth factors and nutrients that nudge them to differentiate into specific cell types.
In the laboratory, scientists have long been able to transform IPS cells into various types of cells, including skin and brain cells. What has been far more difficult, say the researchers, is the ability to turn IPS cells into self-renewing stem cells for a particular organ.
The research team, led by Gabsang Lee, Ph.D., D.V.M., professor of neurology and member of the Institute of Cell Engineering at Johns Hopkins Medicine, coaxed IPS cells to turn into muscle stem cells using a nutrient-rich broth. Further studies are planned, Lee says, to examine the recipe further to determine which ingredients may be key to brewing the muscle stem cells.
Lee is co-founder of Vita Therapeutics Inc., a Baltimore, Maryland-based cell engineering company, that hopes to bring muscle stem cell treatments to market for muscle wasting disorders, including muscular dystrophy. He cautions that such stem cell therapies are not yet available.

With an upcoming U.S. Supreme Court decision that is likely to further restrict abortion access, two new studies from The Ohio State University provide insights into what additional limits on abortion care could mean, particularly for those who will have to travel across state lines.
One study, published this week in the journal Perspectives on Sexual and Reproductive Health, found that proposed abortion bans in Ohio could substantially increase the distance to care for residents of the state. It’s a finding likely to be repeated in restrictive areas throughout the nation, particularly in the South and Midwest, according to the researchers.
The research team analyzed distance to providers under a “best case” scenario (two of Ohio’s five surrounding states continue to offer care) and “worst case” scenario (no surrounding states offer care after the Supreme Court ruling).
In the researchers’ worst-case scenario, they calculated that, from the center of 85 of the state’s 88 counties, travel would be 191 to 339 miles to an abortion provider. In the best-case version, that dropped to 115 to 279 miles away for 62 of 88 Ohio counties.
As of February of this year, the centers of all Ohio counties were, at most, 99 miles away from an abortion facility.
“This summer, the United States Supreme Court will likely overturn or weaken Roe v. Wade when issuing an opinion in the Dobbs v. Jackson Women’s Health Organization case,” said the study’s lead author, Payal Chakraborty, a graduate student in Ohio State’s College of Public Health.

From 2003 through 2020, as opioid-related mortality in Ontario, Canada increased five-fold, the age distribution also shifted downward — with rates now peaking for people in their mid-30s — according to a new study published this week in the open-access journal PLOS ONE by Patrick Brown of University of Toronto, and colleagues.
Opioid-related mortality is a critical public health issue in North America, with rates of opioid-related deaths having increased drastically over recent years. Updated data on the demographic makeup of deaths and how they have changed over time is crucial to tailoring public health interventions.
In the new study, the researchers used mortality data from the Office of the Chief Coroner for Ontario, the most populous province in Canada. Opioid-related deaths were defined as deaths where acute drug toxicity involving opioids was considered as directly contributing to the cause of death.
Between 2003 and 2020, there were 11,633 opioid-related deaths in people aged 15 through 69. Overall, 72% of opioid-related deaths during the 18-year study period were male, and accidental deaths accounted for 82% of the deaths.
Opioid-related mortality rates jumped more than fivefold over this period. They increased substantially for both sexes and across all ages over time, with a downward shifting age distribution for both sexes. Using a novel Bayesian modelling approach, the authors estimated that in 2003, the maximum mortality rate for males, of 5.5 deaths per 100,000 person-years (95% CI 4.0-7.6), was seen around age 44, while in 2020, the maximum of 67.2 deaths per 100,000 person-years (95% CI 55.3-81.5) was at age 35. For females, the greatest mortality rates also shifted to younger ages; in 2003 the peak of 2.2 deaths per 100,000 person-years (95% CI 1.5-3.2) was at age 51, while in 2020, the peak of 16.8 (95% CI 12.8-22.0) was at age 37.
Based on the observed data and resulting models, the researchers hypothesize that opioid-related mortality among the younger population will continue to grow. Targeting strategies to address opioid-related mortality among individuals in the 25 to 44-year age group is of greater importance than in the past, they conclude.
The authors add: “Opioid-related mortality has been rising in Ontario, Canada since 2003, and after a brief decline in part of 2019, the upward trend resumed in the 2020 COVID-19 era. Using a novel Bayesian model and high-frequency data from the coroner’s office, we show that the age distribution of opioid-related mortality has shifted gradually over 18 years from being highest among the 45 to 54-year age group, to being highest among the 25 to 44-year age group.”
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Over time, using antidepressants is not associated with significantly better health-related quality of life, compared to people with depression who do not take the drugs. These are the findings of a new study published this week in the open-access journal PLOS ONE by Omar Almohammed of King Saud University, Saudi Arabia, and colleagues.
It is generally well known that depression disorder has a significant impact on the health-related quality of life (HRQoL) of patients. While studies have shown the efficacy of antidepressant medications for treatment of depression disorder, these medications’ effect on patients’ overall well-being and HRQoL remains controversial.
In the new study, the researchers used data from the 2005-2015 United States’ Medical Expenditures Panel Survey (MEPS), a large longitudinal study that tracks the health services that Americans use. Any person with a diagnosis of depression disorder was identified in the MEPS files. Over the duration of the study, on average there were 17.47 million adult patients diagnosed with depression each year with two years of follow-up, and 57.6% of these received treatment with antidepressant medications.
Use of antidepressants was associated with some improvement on the mental component of SF-12 — the survey tracking health-related quality of life. However, when this positive change was compared to the change in group of people who were diagnosed with depressive disorder but did not take antidepressants, there was no statistically significant association of antidepressants with either the physical (p=0.9595) or mental (p=0.6405) component of SF-12. In other words, the change in quality of life seen among those on antidepressants over two years was not significantly different from that seen among those not taking the drugs.
The study was not able to separately analyze any subtypes or varying severities of depression. The authors say that future studies should investigate the use of non-pharmacological depression interventions used in combination with antidepressants.
The authors add: “Although we still need our patients with depression to continue using their antidepressant medications, long-term studies evaluating the actual impact for pharmacological and non-pharmacological interventions on these patients’ quality of life is needed. With that being said, the role of cognitive and behavioral interventions on the long term-management of depression needs to be further evaluated in an efforts to improve the ultimate goal of care for these patients; improving their overall quality of life.”
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Eggs or yogurt, veggies or potato chips? We make decisions about what to eat every day, but those choices may not be fully our own. New University of Pittsburgh research on mice shows for the first time that the microbes in animals’ guts influence what they choose to eat, making substances that prompt cravings for different kinds of foods.
“We all have those urges — like if you ever you just feel like you need to eat a salad or you really need to eat meat,” said Kevin Kohl, an assistant professor in the Department of Biology in the Kenneth P. Dietrich School of Arts and Sciences. “Our work shows that animals with different compositions of gut microbes choose different kinds of diets.”
Despite decades of speculation by scientists about whether microbes could influence our preferred diets, the idea has never been directly tested in animals bigger than a fruit fly. To explore the question, Kohl and his postdoc Brian Trevelline (A&S ’08), now at Cornell University, gave 30 mice that lacked gut microbes a cocktail of microorganisms from three species of wild rodents with very different natural diets.
The duo found that mice in each group chose food rich in different nutrients, showing that their microbiome changed their preferred diet. The researchers published their work today in the Proceedings of the National Academy of Sciences.
While the idea of the microbiome affecting your behavior may sound far-fetched, it’s no surprise for scientists. Your gut and your brain are in constant conversation, with certain kinds of molecules acting as go-betweens. These byproducts of digestion signal that you’ve eaten enough food or maybe that you need certain kinds of nutrients. But microbes in the gut can produce some of those same molecules, potentially hijacking that line of communication and changing the meaning of the message to benefit themselves.
One such messenger will be familiar to anyone who’s had to take a nap after a turkey dinner: tryptophan.

Portable MRI machines, an emerging technology that makes medical imaging accessible even in remote locations, detected ischemic strokes, or strokes caused by clotting, in 90% of patients scanned, according to a study led by Yale and Harvard researchers.
Previous studies have shown that portable MRI devices can also detect strokes caused by bleeding in the brain, which are distinct from strokes caused by brain clots. The ability of portable MRI machines to differentiate the two types of stroke will help clinicians make crucial life-saving treatment decisions quickly in remote areas for patients who lack ready access to major hospitals with expensive stationary MRI machines, the authors say.
The findings are published April 20 in the journal Science Advances.
“This is the first systematic evidence you can detect ischemic strokes using portable, bedside devices,” said Kevin Sheth, a professor of neurology and neurosurgery at Yale School of Medicine and co-corresponding author of the study.
Outcomes for stroke patients improve dramatically the quicker they receive treatment. But access to stationary MRI machines is limited for those who live far away from major hospitals or in developing countries. And even stroke patients who have access to major hospitals often have to wait for scans with stationary MRIs because of heavy demand for the equipment. Portable scans can be employed at a patient’s bedside, in ambulances, or at clinics in remote areas, Sheth said.
In addition, quickly differentiating between different types of stroke is crucial for determining proper treatment, the researchers say. Ischemic strokes are usually treated with blood thinners. But that course of treatment is dangerous for those who experience hemorrhagic strokes or strokes in which there is bleeding in the brain.
In an analysis of portable MRI scans from 50 patients at Yale New Haven Hospital, the Yale and Harvard researchers found that the results largely confirmed ischemic stroke diagnoses made by stationary MRIs. For 45 of those patients, the portable MRI detected blood clots as small as 4 millimeters in size.
Sheth and his team have received funding from the National Institutes of Health to conduct large-scale studies of portable MRI use in different settings.
Matthew Yuen from the Yale School of Medicine is lead author of the study. W. Taylor Kimberly of Harvard and Massachusetts General Hospital is co-corresponding author.
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