Publisher Health

Mount Sinai researchers have published what they say is the first study to identify a new form of treatment for rapid eye movement (REM) sleep behavior disorder. This condition affects more than 3 million Americans, mostly adults over the age of 50, who often unknowingly physically act out their dreams with vocal sounds or sudden, violent arm and leg movements during slumber, leading to significant injury to themselves or bed partners.
The new study, published in the Journal of Neuroscience on May 25, outlines a novel model to better characterize how REM sleep behavior disorder develops due to neurodegeneration — when brain cells lose function over time — which is associated with the accumulation of tau protein. This model provides an early-life biomarker of impending deterioration of the brain, which could guide future prevention and treatment.
The paper also demonstrates for the first time that sleep medications known as dual orexin receptor antagonists — commonly used to treat insomnia, or difficulty falling and remaining asleep — can significantly reduce REM sleep behavior disorder. Current therapeutic options for this disorder are primarily limited to melatonin and clonazepam, also known as Klonopin, so these findings suggest a promising new treatment with potentially fewer side effects.
“We were interested in understanding all of the ways in which sleep quality breaks down as neurodegeneration progresses and whether there were any ways to mitigate such changes,” said corresponding author Andrew W. Varga, MD, PhD, Associate Professor of Medicine (Pulmonary, Critical Care and Sleep Medicine) at the Icahn School of Medicine at Mount Sinai. “We identify a novel model in which REM sleep behavior disorder can develop, due to neurodegeneration associated with accumulation of tau protein, and a novel therapy that could minimize REM sleep behavior disorder.”
Mount Sinai researchers used a mouse model to study neurodegenerative disorders by examining the brain following abnormal deposits of tau, a protein that normally helps stabilize the internal skeleton of nerve cells in the brain. They analyzed behavioral states including wakefulness, phases of REM (sleep with dreams), phases of non-REM (sleep without dreams), length of sleep, transitions from waking to sleep, and how some factors are related to age. Nearly a third of the older subjects exhibited dream enactment behaviors reminiscent of REM sleep behavior disorder, including chewing and limb extension. After administering a dual orexin receptor antagonist twice during a 24-hour period, to evaluate sleep in light and dark phases, the researchers observed that the medication not only reduced the time it took to fall asleep and increased both the quality and duration of sleep but also reduced levels of dream enactment.
Researchers hope their findings will encourage future trials of dual orexin receptor antagonists to treat REM sleep behavior disorder in humans, given that the medication is already FDA approved and available to treat people with insomnia.
“We anticipated finding breakdown of sleep quality with progressive neurodegeneration related to tau accumulation, but the observation of dream enactment was a surprise,” said lead author Korey Kam, PhD, Assistant Professor of Medicine (Pulmonary, Critical Care and Sleep Medicine) at Icahn Mount Sinai. “It was even more surprising and exciting to observe that a dual orexin receptor antagonist could significantly minimize the dream enactment behaviors.”
The research was supported by funding from the Alzheimer’s Association and Merck Investigator Studies Program.

The many types of cells in the human body are produced through the process of differentiation, in which stem cells are converted to more specialized types. Currently, it is challenging for researchers to control the differentiation of stem cells in the lab (in vitro). Of particular interest are oocytes, which are female germ cells that develop into eggs. Understanding their development could have far-ranging impacts, from infertility treatment to conservation of endangered species. A new study by a Japanese team of researchers led by Dr. Mitinori Saitou has successfully induced meiotic (dividing) oocytes from the embryonic stem cells of cynomolgus monkeys, which share many physiological traits with humans. By establishing a culture method for inducing the differentiation of meiotic oocytes, the researchers aimed to shed light on germ cell development in both humans and other primates. The study’s findings were published in the March 2023 issue of The EMBO Journal.
The team previously reported conditions for inducing oogonia, the precursors of oocytes, by aggregating human primordial germ cell-like cells (hPGCLCs) with cells from the ovaries of female mouse embryos and then culturing them under air-liquid interface conditions1. Similarly, PGCLCs from cynomolgus monkey were induced to differentiate into oogonia but did not progress to meiotic oocytes. To overcome this hurdle, the induced oogonia were isolated and re-aggregated with somatic cells from the ovaries of female mouse embryos and cultured again.
Under these new culture conditions, the cynomolgus monkey oogonia were successfully induced to differentiate into meiotic oocytes, but their development stopped at the second stage of meiosis. Single-cell transcriptome analysis showed that the transcriptomic dynamics of the oocytes in vitro (in the lab) were similar to those of oocytes in vivo (in our body). The researchers also identified differences in gene expression between the in vitro and in vivo oocytes, which suggested a bottleneck for in vitro oocyte development that might lead to the arrest of meiosis in vitro.
Furthermore, by performing whole-genome methylome analysis, the authors found that the induced oocytes were involved in the genome-wide demethylation process in vitro, as seen in mouse and human female germ cell development. They also noticed that demethylation behaved differently in paternally and maternally-derived X chromosomes. These unique methylation dynamics were also found in human oogonia induced in vitro, suggesting that the mechanisms underlying female germ cell development may be the same across primate species. Thus, this culture system might be useful as a model of the primate germ cell differentiation process.
Asked about the potential impact of their study, the authors said that their method of reconstituting multiple steps in the development of female germ cells may help to clarify the molecular mechanisms of primate oocyte development and could one day contribute to the treatment of impaired oocyte development in reproductive medicine. First author Dr. Sayuri Gyobu-Motani says, “We hope that that our culture system can aid in the conservation of endangered species and the creation of in vitro oocyte induction systems for other mammalian species with long lifespans.”

Different types of exercise encourage the formation of different types of muscle fibers, or the cells that make up your muscles. Slow twitch muscle fibers support endurance activities like long-distance running, while fast twitch fibers are needed for short, powerful movements such as those involved in heavy weight lifting. Now, researchers in Japan have shed new light on a family of proteins involved in the development of these muscle fiber types.
In a new study published in Cell Reports, researchers from University of Tsukuba have elucidated the role of a group of proteins known as the large Maf transcription factor family in the specification of fast twitch muscle fibers.
Aerobic exercise encourages muscle fibers to adapt a “slow” identity, while prolonged inactivity — such as that experienced by astronauts on the International Space Station — encourages muscles fibers to adapt a “fast” identity. Previously, the research team from University of Tsukuba discovered that expression of the large Maf family is affected by different gravitational loads. These findings led the researchers to further investigate the role of the large Maf family in the development of muscle fiber types.
“We found that animals subjected to a model of microgravity expressed significantly higher levels of large Mafs in their skeletal muscles,” says senior author of the study Professor Satoru Takahashi. “This seemed to indicate that the large Mafs are induced in muscles experiencing slow-to-fast muscle fiber transition.”
The researchers designed a mouse model in which three Maf family members, Mafa, Mafb, and Maf, were inactivated in the skeletal muscles. These “triple knockout” (TKO) mice exhibited a significant reduction in fast twitch muscle mass compared with control mice, while slow twitch muscle mass appeared to be comparable in TKO and control mice. Additionally, TKO mice lacked a specific subtype of fast twitch fiber, known as type IIb, in the fast twitch muscles.
“The TKO mice had significantly lower average grip strength, but could run longer on a treadmill than control mice, implying that more fast-to-slow muscle fiber conversion had occurred in the absence of large Maf expression,” says lead author of the study Professor Ryo Fujita. “Furthermore, overexpression of the large Mafs in the leg muscles of mice led to a significant increase in type IIb myofibers.”
This study is the first to identify the large Maf proteins as specific regulators of type IIb fast twitch muscle fiber formation. This finding may give new insight on how fast-to-slow muscle fiber transition occurs during aging in mammals and also reveal potential targets for the development of therapies for the treatment of muscular disorders involving fast twitch muscle fibers.
This work was supported by the Grant-in-Aid for the Japan Aerospace Exploration Agency (14YPTK-005512), Grant-in-Aid for Scientific Research on Innovative Area from MEXT (18H04965), the Japan Science and Technology Agency (JPMJPF2017), MEXT Leading Initiative for Excellent Young Researchers, and Ph.D. Program in Humanics (Doctoral Program for World-leading Innovative and Smart Education).

Most living creatures exhibit a circadian rhythm, an internal clock that repeats around every 24 hours. Now, researchers from Japan have found new details about the molecular processes that govern sleep/wake rhythms in mice.
In a recently published study, researchers from the University of Tsukuba have revealed that a key molecule involved in sleep homeostasis (called SIK3 or salt-inducible kinase 3) also plays a critical role in circadian behavior.
Animals are able to adapt to the 24-hour cycle of light and dark in terms of both behavior and physiology via changes in the suprachiasmatic nucleus (SCN), which is the brain’s master clock that synchronizes the various rhythms in the body. However, the biological activities within the SCN that induce time-specific wakefulness have not been fully characterized; the research team aimed to address this.
“Most animals show a peak in activity at a specific point in the circadian cycle,” explains lead author of the study Professor Masashi Yanagisawa. “Because the SCN has been found to regulate sleep and wakefulness at certain times of the day, we wanted to investigate the distinct neurons that control this process.”
To do this, the research team genetically manipulated levels of SIK3 in specific neuron groups in the SCN of mice. Then, they examined sleep and circadian behaviors in the mice, such as when and for how long the mice exhibited activity with respect to the light-dark cycle.
“We found that SIK3 in the SCN can influence circadian cycle length and the timing of peak arousal activity, without changing the daily sleep amount,” says Professor Yanagisawa.
The research team previously reported that SIK3 interacts with LKB1 (an upstream molecule of SIK3) and HDAC4 (an important target of SIK3) in glutamatergic neurons to regulate the amount and depth of sleep. Now, they have found that the SIK3-HDAC4 pathway modulates the length of the circadian period through NMS-producing neurons, and contributes to the sleep/wake rhythm.
The length of the behavioral period and the timing of peak activity are important components of the circadian rhythm. Given the similarities between the circadian systems of different mammals, new information about how this system works in mice could lead to new treatments for sleep and circadian rhythm disorders in humans.
This work was supported by the World Premier International Research Center Initiative (WPI) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (KAKENHI), Japan Science and Technology Agency (JST) Core Research for Evolutional Science and Technology (CREST), Japan Agency for Medical Research and Development (AMED), JSPS DC2 grant, University of Tsukuba Basic Research Support Program Type A, and Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program).

A new tool which could help reduce the spread of antimicrobial resistance is showing early promise, through exploiting a bacterial immune system as a gene editing tool.
Antimicrobial resistance is a major global threat, with nearly five million deaths annually resulting from antibiotics failing to treat infection, according to the World Health Organisation.
Bacteria often develop resistance when resistant genes are transported between hosts. One way that this occurs is via plasmids — circular strands of DNA, which can spread easily between bacteria, and swiftly replicate. This can occur in our bodies, and in environmental settings, such as waterways.
The Exeter team harnessed the CRISPR-Cas gene editing system, which can target specific sequences of DNA, and cuts through them when they are encountered. The researchers engineered a plasmid which can specifically target the resistance gene for Gentamicin — a commonly used antibiotic.
In laboratory experiments, the new research, published in Microbiology, found that the plasmid protected its host cell from developing resistance. Furthermore, researchers found that the plasmid effectively targeted antimicrobial resistant genes in hosts to which it transferred, reversing their resistance.
Lead author David Walker-Sünderhauf, of the University of Exeter, said: “Antimicrobial resistance threatens to outstrip covid in terms of the number of global deaths. We urgently need new ways to stop resistance spreading between hosts. Our technology is showing early promise to eliminate resistance in a wide range of different bacteria. Our next step is to conduct experiments in more complex microbial communities. We hope one day it could be a way to reduce the spread of antimicrobial resistance in environments such as sewage treatment plants, which we know are breeding grounds for resistance.”
The research is supported by GW4, the Medical Research Council, the Lister Institute, and JPI-AMR. The paper is entitled ‘Removal of AMR plasmids using a mobile, broad host-range, CRISPR-Cas9 delivery tool’, and is published in Microbiology.

The Korea Advanced Institute of Science and Technology (KAIST) and their collaborators have conducted a groundbreaking study targeting ‘jumping genes’ in the entire genomes of the human large intestine. Published in Nature on May 18 2023, the research unveils the surprising activity of ‘Long interspersed nuclear element-1 (L1),’ a type of jumping gene previously thought to be mostly dormant in human genomes. The study shows that L1 genes can become activated and disrupt genomic functions throughout an individual’s lifetime, particularly in the colorectal epithelium.
With approximately 500,000 L1 jumping genes, accounting for 17% of the human genome, they have long been recognized for their contribution to the evolution of the human species by introducing ‘disruptive innovation’ to genome sequences. Until now, it was believed that most L1 elements had lost their ability to jump in normal tissues of modern humans. However, this study reveals that some L1 jumping genes can be widely activated in normal cells, leading to the accumulation of genomic mutations over an individual’s lifetime. The rate of L1 jumping and resulting genomic changes vary among different cell types, with a notable concentration observed in aged colon epithelial cells. The study illustrates that every colonic epithelial cell experiences an L1 jumping event by the age of 40 on average.
The research, led by co-first authors Chang Hyun Nam (a graduate student at KAIST) and Dr. Jeonghwan Youk (former graduate student at KAIST and assistant clinical professor at Seoul National University Hospital), involved the analysis of whole-genome sequences from 899 single cells obtained from skin (fibroblasts), blood, and colon epithelial tissues collected from 28 individuals. The study uncovers the activation of L1 jumping genes in normal cells, resulting in the gradual accumulation of genomic mutations over time. Additionally, the team explored epigenomic (DNA methylation) sequences to understand the mechanism behind L1 jumping gene activation. They found that cells with activated L1 jumping genes exhibit epigenetic instability, suggesting the critical role of epigenetic changes in regulating L1 jumping gene activity. Most of these epigenomic instabilities were found to arise during the early stages of embryogenesis. The study provides valuable insights into the aging process and the development of diseases in human colorectal tissues.
“This study illustrates that genomic damage in normal cells is acquired not only through exposure to carcinogens but also through the activity of endogenous components whose impact was previously unclear. Genomes of apparently healthy aged cells, particularly in the colorectal epithelium, become mosaic due to the activity of L1 jumping genes,” said Prof. Young Seok Ju at KAIST.
“We emphasize the essential and ongoing collaboration among researchers in clinical medicine and basic medical sciences,” said Prof. Min Jung Kim of the Department of Surgery at Seoul National University Hospital. “This case highlights the critical role of systematically collected human tissues from clinical settings in unraveling the complex process of disease development in humans.”
“I am delighted that the research team’s advancements in single-cell genome technology have come to fruition. We will persistently strive to lead in single-cell genome technology,” said Prof. Hyun Woo Kwon of the Department of Nuclear Medicine at Korea University School of Medicine.
The research team received support from the Research Leader Program and the Young Researcher Program of the National Research Foundation of Korea, a grant from the MD-PhD/Medical Scientist Training Program through the Korea Health Industry Development Institute, and the Suh Kyungbae Foundation.

Patients with MS show structural abnormalities in their white matter even before MS inflammation develops. This is the conclusion of a new study by the Netherlands Institute for Neuroscience (NIN) in Amsterdam and the Max Planck Institute for Multidisciplinary Sciences in Göttingen (MPI). Could this finding be a target for a new treatment to prevent MS inflammation?
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. In early, as well as advanced progressive MS, lesions arise along with substantial inflammatory activity. Lesions are the inflammatory sites where the myelin is broken down and taken up by microglial cells (our brain’s immune cells). But do we see something in the tissue even before these inflammation spots appear?
To answer this question, Aletta van den Bosch of the research team of Inge Huitinga (NIN) and Wiebke Moebius (MPI) looked into human post-mortem brains of MS patients and controls that have been donated to the Dutch Brain Bank. Their focus was particularly on the so-called ‘normal-appearing white matter’. As the name suggests, these are areas where lesions have not formed yet, and so still appear normal. How is it possible that people with MS develop lesions here later and people without MS do not?
The team took a detailed look at myelin to see if there are early changes in people with MS. Myelin is an insulating white, fatty substance that is wrapped up to 150 times around the nerve fibers. At regular distances from each other there are interruptions of the myelin, these are the Nodes of Ranvier. During the transmission of electrical signals, the signal jumps from one Node or Ranvier to the next, allowing a myelin-containing fiber to transmit a signal 100 times faster than without myelin. In people with MS, myelin is damaged and signal transmission in the central nervous system is disrupted, which can impair functions such as walking and vision. What kinds of changes in brain tissue can we observe in the early stages of MS?
Ultra-strong microscope
Aletta van den Bosch: ‘To be able to study myelin properly, we looked at the optic nerve. In this area, all nerve fibers and their myelin follow the same direction very nicely, so that we can visualize the myelin well. We did this by using electron microscopy. With this technique we zoomed in 5,000 to 30,000 times on a cross-section of a nerve-fiber.’
‘In MS, myelin was found to be less tightly wrapped around the nerve-fiber. This means that the fiber is not properly insulated which has major consequences: the signal can’t be transmitted as fast as it used to be. We saw that where myelin was less attached to the fiber, there was a disruption of the nodes of Ranvier combined with increased levels of T-cells and activated microglia. Furthermore, there were more mitochondria. Mitochondria are the energy factories of the cell, so this phenomenon may indicate that more energy is needed for signal movement and maintenance of the fibers.’
Harmful by-products
‘Although mitochondria are generally good for energy production, they also produce many by-products, such as oxygen radicals. We suspect this to be an amplifying factor for myelin breakdown: the myelin is already in a bad state, more mitochondria develop to provide more energy, which then makes conditions even worse. The theory is that a threshold value is needed to initiate the breakdown. It is also possible that the body recognizes the detached myelin as ‘abnormal’, which could be the start of breakdown by immune cells.’
‘We haven’t been able to look at human tissue in such detail before, meaning that almost all the research so far has been done in laboratory animals. Although this is very valuable research, it could sometimes be more difficult to translate the results directly to humans. This is the first glimpse into what happens at the ultrastructural level in people with MS and what exactly leads to the lesions. You need very good tissue to do this which is why the brain bank is so crucial for our research.”
Future perspective
‘The next step is to see if we can prevent the myelin from winding so loosely around nerve endings. First, we want to experiment in culture dishes to see if we can make the wrapping of myelin stronger. Subsequently, we will have perform tests in laboratory animals, and eventually we will be able to take the step to humans. It would be great if we could find something to prevent myelin detachment. While this will not prevent the damage of the lesions that are already there, it might prevent the development of new lesions. This would provide a whole new target for MS treatment.”

Mobility limitation is an initial stage of human mobility disability and an early sign of functional decline. It can manifest as muscle weakness, loss of balance, unsteady gait, and joint pain. Long-term and continuous monitoring of joint motion may potentially prevent or delay decline by allowing the early diagnosis, prognosis, and management of mobility-related conditions.
This long-term and continuous monitoring is made possible by analysis systems that are either non-wearable or wearable. Non-wearable systems are reliable, but require a laboratory environment and trained individuals and are therefore impractical for daily use. On the other hand, wearable systems are portable, cheaper, and much easier to use. Unfortunately, typical wearable sensors tend to be inflexible and bulky.
A relatively new player to the wearable systems field are wearables made from conductive fabric (CF), which are soft, lightweight, malleable, and non-invasive. These sensors are comfortable and suitable for long-term monitoring. However, most CF-based wearables become error-prone if displaced from their intended location and rely on external components that restrict the sensitivity and working range of the sensors.
To overcome these limitations, a research team created a wearable with a high degree of functional and design freedom. Associate Professor Low Hong Yee and her colleagues from the Singapore University of Technology and Design (SUTD) collaborated with Dr Tan Ngiap Chuan of SingHealth Polyclinics and published their research paper, ‘All knitted and integrated soft wearable of high stretchability and sensitivity for continuous monitoring of human joint motion’ in Advanced Healthcare Materials.
According to Associate Professor Low, their key considerations when designing the wearable were sensor data accuracy and reliability and for the sensor to rely on as few external components as possible. The result was a highly stretchable, fully functional sensing circuit made from a single fabric. Because the knee joint is important for lower limb mobility, the wearable was designed for the knee.
To develop this single-fabric circuit, the team mechanically coupled an electrically conductive yarn with a dielectric yarn of high elasticity in various stitch patterns. Dimensions were customised according to the subject’s leg. The functional components — sensors, interconnects, and resistors — formed a stretchable circuit on the fully knitted wearable that allowed real-time data to be obtained.

However, putting together sensors, interconnects, and resistors in a single stretchable knit is difficult. Associate Professor Low mentioned that “the synergy of yarns with different electrical and mechanical properties to achieve high signal sensitivity and high stretchability” was challenging, as the desired properties for each component were vastly different.
Sensors need to produce a large change in resistance for enhanced sensitivity, while interconnects and resistors need fixed resistances of the highest and lowest values, respectively. As such, the researchers optimised yarn composition and stitch type for each component before connecting the functional circuit to a circuit board contained in a pocket of the wearable, allowing for wireless transmission of real-time data.
With a soft knee wearable developed, its components functional, and data transmission possible, it was time to test the performance of the wearable. The team assessed the wearable through extension-flexion, walking, jogging, and staircase activities. Subjects wore the knee wearable together with reflective markers that were detected by a motion capture system, allowing the comparison between sensor data and actual joint movement.
The sensor response time was less than 90 milliseconds for a step input, which is fast enough to monitor the human movements included in the study. Additionally, the smallest change in joint angle that the sensors could detect was 0.12 degrees. The sensor data showed strong correlation with joint movement data acquired from the motion capture system, demonstrating reliability of the sensor data.
The potential impact of such device in the medical field is huge. Long-term continuous monitoring of joint motion is important to track mobility-related conditions. Often, people ignore early signs of mobility decline as they are not deemed serious enough to seek help. Wearable technology solves this problem by assessing a user’s mobility directly in real-time.
Embedding a user-friendly sensor circuit into a soft and comfortable fabric may increase the public’s adoption of wearable technology, especially among athletes and the elderly. Data can be gathered in real-time and translated into indicators that can detect mobility decline. When signs of mobility decline are found, preventive care, prognosis, and management of the healthcare condition can be given.
Building on this work, the team intends to study the effect of sweat and humidity on sensor signals and to extend the research to include subjects from both healthy and unhealthy populations in the future. “We have started working on extending the wearable to special user groups and to monitor other body joints, such as the shoulder,” stated Associate Professor Low. “We’re also looking at securing an incubation fund to explore the commercialisation potential of the wearable.”
Video: https://youtu.be/KPlSPtDVs2k

The George Institute for Global Health today announced data from the phase III INTERACT3 study demonstrating that a new combination of treatments for stroke due to intracerebral haemorrhage (ICH) significantly improves the chances of surviving without major disability. Results were presented today at the European Stroke Organisation Conference in Munich, Germany, and simultaneously published in The Lancet.
The INTERACT3 study is the first-ever randomised controlled trial to show a clearly positive outcome for the treatment of ICH. Timely administration of the new treatment protocol — known as a Care Bundle — centred on the rapid control of high blood pressure, led to improved recovery, lower rates of death, and better overall quality of life in patients with this serious condition.
Professor Craig Anderson, Director of Global Brain Health at The George Institute and a senior author of the research said, “Despite the high rates of ICH and its severity, there are few proven options for treating it, but early control of high blood pressure is the most promising. Time is critical when treating this type of stroke, so we tested a combination of interventions to rapidly stabilise the condition of these patients to improve their outcomes. We estimate that if this protocol was universally adopted, it could save tens of thousands of lives each year around the world.”
Commonly referred to as a haemorrhagic stroke or brain bleed, ICH is the second most common type of stroke and also the most deadly, with 40% to 50% of patients dying within 30 days. It occurs when blood leaks out of a blood vessel into the brain tissue and represents over a quarter of all cases of stroke, affecting approximately 3.4 million people a year.
In the INTERACT3 study, over 7,000 patients were enrolled across 144 hospitals in 10 countries — nine middle-income countries and one high-income country.
The research team evaluated the effectiveness of the new Care Bundle, which included early intensive lowering of systolic blood pressure, strict glucose control, fever treatment, and rapid reversal of abnormal anticoagulation.
They found that using this new treatment protocol compared to usual care reduced the likelihood of a poor functional outcome, including death, after six months. This was estimated to prevent one additional death for every 35 patients treated.
Central to this was a rapid reduction in systolic blood pressure, where target levels were achieved, on average, in 2.3 hours [range 0.8 to 8.0hrs], compared to 4.0 hours [range 1.9 to 16.0hrs] in the control group. The interventional protocol resulted in a statistically significant reduction in mortality, number of serious adverse events, and time spent in hospital, as well as demonstrating an improvement in health-related quality of life.
The burden of ICH is greatest in low- and middle-income countries. In 2019, 30% of all stroke cases in LMICs were ICH, almost double the proportion seen in high-income countries (16%). This is in part due to high rates of hypertension and limited resources for primary prevention strategies, including identification and management of stroke risk factors by healthcare services.
Dr Lili Song, joint lead author and Head of the Stroke Program at The George Institute China, said, “A lack of proven treatments for ICH has led to a pessimistic view that not much can be done for these patients. However, with INTERACT3, we demonstrate on a large scale how readily available treatments can be used to improve outcomes in resource-limited settings. We hope this evidence will inform clinical practice guidelines across the globe and help save many lives.”

In an analysis of the Look AHEAD study, researchers from the Brigham and Joslin Diabetes Center found that participants who were physically active in the afternoon had greater reductions in blood sugar than those who were most active at other times of day.
Over 37 million Americans have diabetes, and 90-95% of that population are diagnosed with type 2 diabetes. Lifestyle interventions, such as a healthy diet and a regular physical activity program, are methods to manage diabetes. A new study from a collaboration of investigators at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, and Joslin Diabetes Center, part of Beth Israel Lahey Health, uses data from the Look AHEAD (Action for Health in Diabetes) study, a randomized controlled trial that compared an intensive lifestyle intervention with diabetes support and education in patients diagnosed with type 2 diabetes and overweight or obesity to track the development of cardiovascular disease over time. In the current study, the research team assessed whether physical activity at certain times of day was associated with greater improvement in blood glucose control. Their findings suggest patients with type 2 diabetes who were physically active in the afternoon had the largest improvements after one year in the trial. The team’s results are published in Diabetes Care.
“In this study, we shown that adults with type 2 diabetes had the greatest improvement in glucose control when they were most active in the afternoon,” said co-corresponding author Jingyi Qian, PhD, from the Division of Sleep and Circadian Disorders at the Brigham. “We’ve known that physical activity is beneficial, but what our study adds is a new understanding that timing of activity may be important too.”
Physicians recommend that patients with diabetes participate in regular physical activity as a method to manage their blood glucose levels. Elevated blood glucose levels can put people with type 2 diabetes at risk of heart disease, vision impairment, and kidney disease.
The team analyzed physical activity data from the first and fourth years of the Look AHEAD study, which included data from over 2,400 participants. During the study, participants wore a waist accelerometry recording device to measure physical activity. When the Brigham and Joslin team reviewed the data from year 1, they determined that those who engaged in moderate-to-vigorous physical activity in the afternoon had the greatest reduction in blood glucose levels. Upon comparing the data from year 4, the afternoon group maintained a reduction in blood glucose levels. In addition, the afternoon group also had the highest chance of stopping their glucose-lowering/diabetes medications.
The Brigham and Joslin team note that their investigation has limitations; for example, their study is observational and does not measure confounding factors like sleep and dietary intake.
In future studies, the team may test their findings experimentally to investigate the underlying mechanisms that may explain why time of day of activity may influence blood glucose control. From this, the team may be able to provide specific physical activity recommendations for patients.
“Timing does seem to matter,” said co-corresponding author Roeland Middelbeek, MD, assistant investigator at Joslin Diabetes Center. “Going forward, we may have more data and experimental evidence for patients to give more personalized recommendations.”
Funding: This study was funded by the National Heart, Lung, and Blood Institute (K99-HL-148500, R01-HL140574), National Institute on Aging (RF1AG059867 and RF1AG064312), and National Institute of