Publisher Health

Whether it’s work or play that prevents us from getting enough shut-eye during the week, assuming we can make up for it by sleeping in over the weekend is a mistake. New research led by Penn State reveals that cardiovascular health measures, including heart rate and blood pressure, worsen over the course of the week when sleep is restricted to five hours per night, and attempting to catch up on sleep over the weekend is insufficient to return these measures to normal.
“Only 65% of adults in the U.S. regularly sleep the recommended seven hours per night, and there’s a lot of evidence suggesting that this lack of sleep is associated with cardiovascular disease in the long term,” said Anne-Marie Chang, associate professor of biobehavioral health and co-author of the work, published in the journal Psychosomatic Medicine. “Our research reveals a potential mechanism for this longitudinal relationship, where enough successive hits to your cardiovascular health while you’re young could make your heart more prone to cardiovascular disease in the future.”
The team recruited 15 healthy men between the ages of 20 and 35 to participate in an 11-day inpatient sleep study. For the first three nights, the participants were allowed to sleep up to 10 hours per night to achieve a baseline sleep level. For the next five nights, the participants’ sleep was restricted to five hours per night, followed by two recovery nights, in which they were again allowed to sleep up to 10 hours per night. To evaluate the effects of this sleep regime on cardiovascular health, the researchers measured the participants’ resting heart rates and blood pressure every two hours during the day.
Chang explained that the team’s study is unique because it measured heart rate and blood pressure multiple times throughout the day for the duration of the study, which enabled them to account for any effects that time of day might have on heart rate and blood pressure. For example, heart rate is naturally lower upon waking than later in the day, so measuring heart rate multiple times throughout the day can account for this difference.
The team, which included David Reichenberger, lead author and graduate student in biobehavioral health, Penn State, found that heart rate increased nearly one beat per minute (BPM) with each successive day of the study. Specifically, the average baseline heart rate was 69 BPM, while the average heart rate by the end of the study on the second day of recovery was nearly 78 BPM. Systolic blood pressure also increased by about 0.5 millimeters of mercury (mmHg) per day. The average baseline systolic blood pressure was 116 mmHg and was nearly 119.5 mmHg by the end of the recovery period.
“Both heart rate and systolic blood pressure increased with each successive day and did not return to baseline levels by the end of the recovery period,” Reichenberger said. “So, despite having additional opportunity to rest, by the end of the weekend of the study, their cardiovascular systems still had not recovered.”
Chang noted that longer periods of sleep recovery may be necessary to recover from multiple, consecutive nights of sleep loss.
“Sleep is a biological process, but it’s also a behavioral one and one that we often have a lot of control over,” Chang said. “Not only does sleep affect our cardiovascular health, but it also affects our weight, our mental health, our ability to focus and our ability to maintain healthy relationships with others, among many other things. As we learn more and more about the importance of sleep, and how it impacts everything in our lives, my hope is that it will become more of a focus for improving one’s health.”
Other Penn State authors on the paper include Stephen Strayer, former graduate student in neuroscience; Margeaux Schade, assistant research professor of biobehavioral health; and Orfeu Buxton, Elizabeth Fenton Susman Professor of Biobehavioral Health. Kelly Ness, postdoctoral fellow, University of Washington, and Gina Marie Mathew, postdoctoral associate, Stony Brook University, also are authors.

Researchers at Lund University have developed a technique for simultaneously measuring electrical signals from 128 areas of the brain in awake rats. They have then used the information to measure what happens to the neurons when the rats are given psychedelic drugs. The results show an unexpected and simultaneous synchronisation among neurons in several regions of the brain.
The idea that electrical oscillations in the brain could be used to teach us more about our experiences was conceived several years ago. Pär Halje and the research team was studying rats with Parkinson’s disease that had problems with involuntary movements. The researchers discovered a tone — an oscillation or wave in the electrical fields — of 80 hertz in the brains of the rats with Parkinson’s disease. It turned out that the wave was closely connected to the involuntary movements.
“A Polish researcher had observed similar waves after giving rats the anaesthetic ketamine. The ketamine was given at a low dose so that the rats were conscious, and the equivalent dose in a human causes psychedelic experiences. The waves they saw were in more cognitive regions of the brain than in the rats with Parkinson’s, and the frequency was higher, but that still made us consider whether there were links between the two phenomena. Perhaps excessive brain waves in the motor regions of the brain cause motor symptoms, while excessive waves in cognitive regions give cognitive symptoms,” says Pär Halje, researcher in neurophysiology at Lund University.
The research team that Pär Halje belongs to has developed a method that uses electrodes to simultaneously measure oscillations from 128 separate areas of the brain in awake rats. The electrical waves are caused by the cumulative activity in thousands of neurons, but the researchers also succeeded in isolating signals from individual neurons.
“For several of these areas, it is the first time anyone has successfully shown how individual neurons are affected by LSD in awake animals. When we gave the rats the psychedelic substances LSD and ketamine, the waves were clearly registered.”
Collective wave patterns
Despite ketamine and LSD affecting different receptors in the brain — they have completely different ways into the nervous system — they resulted in the same wave patterns even if the signals from individual cells differed. When the rats were given LSD, researchers saw that their neurons were inhibited — they signalled less — in all parts of the brain. Ketamine seemed to have a similar effect on the large neurons — pyramidal cells — which saw their expression inhibited, while interneurons, which are smaller neurons that are only collected locally in tissue, increased their signalling.

The universe is humming with gravitational radiation — a very low-frequency rumble that rhythmically stretches and compresses spacetime and the matter embedded in it.
That is the conclusion of several groups of researchers from around the world who simultaneously published a slew of journal articles in June describing more than 15 years of observations of millisecond pulsars within our corner of the Milky Way galaxy. At least one group — the North American Nanohertz Observatory for Gravitational Waves (NANOGrav) collaboration — has found compelling evidence that the precise rhythms of these pulsars are affected by the stretching and squeezing of spacetime by these long-wavelength gravitational waves.
“This is key evidence for gravitational waves at very low frequencies,” says Vanderbilt University’s Stephen Taylor, who co-led the search and is the current chair of the collaboration. “After years of work, NANOGrav is opening an entirely new window on the gravitational-wave universe.”
Gravitational waves were first detected by the Laser Interferometer Gravitational-Wave Observatory (LIGO) in 2015. The short-wavelength fluctuations in spacetime were caused by the merger of smaller black holes, or occasionally neutron stars, all of them weighing in at less than a few hundred solar masses.
The question now is: Are the long-wavelength gravitational waves — with periods from years to decades — also produced by black holes?
In one paper from the NANOGrav consortium, published Aug. 1 in The Astrophysical Journal Letters (ApJ Letters), University of California, Berkeley, physicist Luke Zoltan Kelley and the NANOGrav team argued that the hum is likely produced by hundreds of thousands of pairs of supermassive black holes — each weighing billions of times the mass of our sun — that over the history of the universe have gotten close enough to one another to merge. The team produced simulations of supermassive black hole binary populations containing billions of sources and compared the predicted gravitational wave signatures with NANOGrav’s most recent observations.
The black holes’ orbital dance prior to merging vibrates spacetime analogous to the way waltzing dancers rhythmically vibrate a dance floor. Such mergers over the 13.8-billion-year age of the universe produced gravitational waves that today overlap, like the ripples from a handful of pebbles tossed into a pond, to produce the background hum. Because the wavelengths of these gravitational waves are measured in light years, detecting them required a galaxy-sized array of antennas — a collection of millisecond pulsars.

The first gene mapping study on human scalp hair whorls not only shows that hair whorl direction has a genetic basis, but also that it is affected by multiple genes. Four associated genetic variants that are likely to influence hair whorl direction are identified, as reported in the Journal of Investigative Dermatology, published by Elsevier.
A hair whorl is a patch of hair growing in a circular pattern around a point specified by hair follicle orientations. As an easily observed human trait, scalp hair whorl pattern is typically defined by the whorl number (single or double whorl) and whorl direction (e.g., clockwise, counterclockwise, or diffuse).
Because atypical whorl patterns have been observed in patients with abnormal neurological development, understanding the genetic basis of whorl patterns may help unravel important biological processes.
The first genome-wide association study (GWAS) on human scalp hair whorls was performed among 2,149 Chinese individuals from the National Survey of Physical Traits cohort, followed by a replication study in 1,950 Chinese individuals from the Taizhou Longitudinal Study cohort.
Lead investigator Sijia Wang, PhD, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, explained, “We know very little about why we look like we do. Our group has been looking for the genes underlying various interesting traits of physical appearance, including fingerprint patterns, eyebrow thickness, earlobe shape and hair curliness. Hair whorl is one of the traits that we were curious about. The prevailing opinion was that hair whorl direction is controlled by a single gene, exhibiting Mendelian inheritance. However, our results demonstrate that hair whorl direction is influenced by the cumulative effects of multiple genes, suggesting a polygenic inheritance.”
The study identifies four associated genetic variants (at 7p21.3, 5q33.2, 7q33, and 14q32.13). These genetic variants are likely to influence hair whorl direction by regulating the cell polarity of hair follicles, with cranial neural tube closure and growth also potentially playing a role.
Professor Wang continued, “While previous work proposed the hypothesis of associations between hair whorl patterns and abnormal neurological development, no significant genetic associations were observed between hair whorl direction and behavioral, cognitive, or neurological phenotypes. Although we still know very little about why we look like we do, we are confident that curiosity will eventually drive us to the answers.”

Innovative technology that creates ultra-thin layers of human cells in tube-like structures could spur development of lifelike blood vessels and intestines in the lab.
The technique, known as RIFLE — rotational internal flow layer engineering — enables the construction of separate layers as delicate as one cell thick.
Such versatility is crucial to developing accurate human models of layered tubular tissue for use in research, offering an important alternative to animal models, experts say.
Scientists have been able to demonstrate the technology by manufacturing cells into super-thin layers that mirror those seen in a human blood vessel.
Layered tubular tissue is found throughout the body — in blood vessels, the digestive tract and other organs. It can feature multiple cell types, generating layers with different properties and functions.
Current methods used to manufacture human tissue in the lab — known as biofabrication — can lack the detail needed to mimic these complex structures.
Developed by experts at the University of Edinburgh, RIFLE is a low-cost and fast biofabrication method that can work to a very small scale.

The impact of particulate matter air pollution on death and disability is on the rise worldwide, according to new research published today in the Journal of the American Heart Association, an open access, peer-reviewed journal of the American Heart Association.
Previous research established the association of particulate matter (PM) pollution to CVD death and disability. However, questions remain about the worldwide impact from this type of pollution and how it has been changing over time, the study authors noted.
“We focused on examining the burden globally because particulate matter pollution is a widespread environmental risk factor that affects all populations worldwide, and understanding its impact on cardiovascular health can help guide public health interventions and policy decisions,” said Farshad Farzadfar, M.D., M.P.H., D.Sc., senior author of the study and a professor of medicine in the non-communicable diseases research center of the Endocrinology and Metabolism Research Institute at Tehran University of Medical Sciences in Iran.
The researchers analyzed PM pollution as a risk factor for death and disability using freely available data from 204 countries collected between 1990 and 2019 and detailed in the Global Burden of Disease (GBD) study. Exposure to PM pollution was estimated using a tool from the 2019 update to the GBD study that incorporated information from satellite and ground-level monitoring, computer models of chemicals in the atmosphere and land-use data.
Among the many types of heart disease, the current analysis of cardiovascular disease is restricted to stroke and ischemic heart disease (a lack of blood and oxygen supply to portions of the heart, usually due to plaque build-up in the arteries) because the 2019 GBD study on the global burden of disease attributed to PM pollution only examined these two diagnoses. The Institute for Health Metrics and Evaluation (IHME), which provides the GBD estimates, only reports data for a certain risk factor if there is a large body of evidence about its association with a disease, Farzadfar noted.
“Until now, only the association of PM pollution with ischemic heart disease and stroke has been demonstrated in a large number of studies,” Farzadfar said. “The IHME may include other CVDs in the future. Moreover, ischemic heart disease and stroke contribute to a significant majority of CVDs, and our estimates, despite having limitations, may be used as a good estimate of PM pollution burden on CVDs.”
The investigators analyzed changes over time in years of life lost due to premature death (YLLs), years lived with disability (YLDs) and disability-adjusted life years (DALYs). DALYs is a measure that considers both the loss of life and the impact on quality of life to assess the full impact of a health condition on a population. The cardiovascular disease burden was assessed both overall and with age standardization, which compares health outcomes across a population with a wide range of ages.

Scientists at St. Anna Children’s Cancer Research Institute and the Eberhard Karls University of Tübingen have shown that immunotherapy after stem cell transplantation effectively combats certain nerve tumors in children. Crucially, stem cells from a parent provide children with a new immune system that responds much better to immunotherapies. These results of an early clinical trial were published in the  Journal of Clinical Oncology.
Childhood tumors of the nervous system, known as neuroblastomas, are associated with an unfavorable prognosis if the tumor is classified as a high-risk type. The chances are particularly poor for patients in the relapsed stage. In this case, immunotherapy following stem cell transplantation is now associated with long-term survival in a substantial proportion of the patients included in a recent study. Compared to an earlier study the survival rate was increased.
“After the transplantation of stem cells from a parent, the patients are equipped with a new immune system. This enables a better immune response to the subsequent immunotherapy and clearly improves the outcome,” explains Prof. Ruth Ladenstein, MD, head of the Studies & Statistics group for Integrated Research and Projects (S2IRP) at St. Anna Children’s Cancer Research Institute and professor at the Department of Pediatrics and Adolescent Medicine at MedUni Vienna, who played a key role as co-first author.
Long-term survival exceeds 50 percent
“After a median follow-up of about eight years, we see that more than half of the study patients live five years or longer with their disease,” Prof. Ladenstein reports (5-year overall survival: 53%). In comparison, the 5-year overall survival in an earlier study, in which stem cell transplantation was not followed by immunotherapy, was only 23 percent. Those patients who showed a complete or partial response to prior treatment had significantly better survival.
“In summary, immunotherapy with dinutuximab beta following transplantation of stem cells from matched family donors resulted in remarkable outcomes when patients had at least a partial response to prior treatment,” says Prof. Ladenstein. “In our study, there were no unexpected side effects and the frequency of graft-versus-host-disease was low.”
Boosting natural killer cells
Dinutuximab beta is an antibody that binds to a specific molecule (GD2) on the surface of tumor cells, marking them for destruction by the immune system. Subsequently, specific immune cells, known as natural killer cells, can attack the tumor. However, prior chemotherapies may impair certain abilities of natural killer cells. “Therefore, a transplantation of intact natural killer cells from matched family donors seems reasonable before immunotherapy is administered. The transplanted, new natural killer cells are now able to target the tumor cells more efficiently — by means of an antibody-dependent reaction,” explains Prof. Ladenstein.
According to the authors, further studies are needed to determine the individual components of the therapeutic approaches. Recently, conventional chemotherapy has also been combined with immunotherapy early in the treatment strategy, resulting in similarly improved response rates. However, the hope is that the concept of a renewed immune system through a healthy parent in combination with the described transplantation procedure could further increase survival rates: “Our approach could thus result in stronger and longer lasting tumor control. A randomized study would be necessary to scientifically substantiate the additional potential benefit of a new immune system in the context of relapse therapy,” Prof. Ladenstein adds.

A collaborative study between LSU Health New Orleans School of Medicine, the University of Rochester and Cellestia Biotech AG, a biopharmaceutical company headquartered in Basel, Switzerland, provides compelling evidence that combining an investigational oral drug with standard-of-care medications reverts hormone resistance and increases Rx effectiveness in experimental models of estrogen-receptor positive (ER+) and triple-negative breast cancers (TNBC), respectively. The findings are published online in MDPI Cancers, available here.
CB-103 is a small molecule Notch inhibitor invented by Cellestia. Notch receptors relay information from the cell surface to the genes, and Notch signaling plays an important role in many different cancers, including breast cancers, where its role was originally demonstrated by the Miele laboratory. Based on their prior research, the LSU Health team believed this compound should be safe and effective in hormone-resistant estrogen-receptor-positive breast cancers and proposed the study for this indication to Cellestia.
“Over the past two decades, various drugs targeting the Notch signaling axis have been investigated,” notes senior author Lucio Miele, MD, PhD, Professor and Chair of Genetics and Assistant Dean for Translational Science at LSU Health New Orleans School of Medicine. “CB-103 is a next-generation, orally active, clinical-stage drug that, unlike older drugs, directly targets gene regulation by Notch and offers a much-improved toxicity profile.”
“The safety and efficacy of CB-103 in Notch-dependent advanced, metastatic solid, or hematological malignancies have been investigated in a multi-center international phase I/II clinical trial,” adds Samarpan Majumder, PhD, Assistant Professor of Genetics at LSU Health New Orleans School of Medicine and one of the senior authors of the paper. “CB-103 has been safe and well-tolerated, showing minimal gastrointestinal toxicity, unlike previous Notch inhibitors.”
Despite recent advances in the treatment of estrogen-receptor-positive breast cancers, endocrine resistance ultimately develops. Available second-line therapies are moderately effective but can have significant toxicities, and third-line therapies are generally largely ineffective. Triple-negative breast cancer is an aggressive breast cancer subtype that accounts for 15-25% of all breast cancer diagnoses in Western countries. Patients with early TNBC have a two- to three-fold higher risk of disease recurrence and death in the first three years after diagnosis. TNBC disproportionately affects young premenopausal women and African American women.
“Our translational data will be serving as a foundation for planned clinical trials where we will combine CB-103 with anti-estrogen therapy in ER+ breast cancers and with taxanes like taxol or docetaxel in TNBC,” concludes Dr. Majumder.
LSU Health New Orleans co-authors include Drs. Giulia Monticone, Jovanny Zabaleta, Fokhrul Hossain, Dorota Wyczechowska, and Luis Del Valle. Other co-authors are from Cellestia Biotech and the University of Rochester.
The research was funded by Cellestia Biotech and the Cancer Crusaders Chair at LSU Health New Orleans.

Breastfeeding has long been used as a method to help keep newborns healthy and protected against a variety of diseases. But certain sugars naturally found in breastmilk could also help prevent infections before a baby arrives. Researchers reporting in ACS Central Science have found that these sugars can stop a common prenatal infection in human tissues and pregnant mice. This could someday help avoid preterm births or complications without the need for additional antibiotics.
One of the most common bacteria that can affect pregnancies is Group B streptococcus (GBS). If left untreated, GBS infections can potentially lead to adverse effects, including neonatal pneumonia or preterm birth. Though treatments are available, they primarily rely on antibiotics, which can give rise to resistant strains. However, many of the compounds already present in human breast milk, such as human milk oligosaccharides (HMOs), naturally have antibacterial effects. Previously, Steven Townsend, Jennifer Gaddy and colleagues explored the antimicrobial effects of HMOs, finding that they could inhibit growth of GBS in vitro and in certain reproductive cells. But before the compounds could be used to boost existing antibiotics or become a new therapeutic option entirely, researchers need to show how the sugars work in many tissues and in vivo. So now, the team wanted to investigate HMO activity in GBS infections in pregnant mice and human tissues.
The team first analyzed the protective effects of HMOs on human tissue infected with GBS, using both ex vivofetal tissues and an organoid model of the vagina. When they added a mixture of HMOs designed to mimic the sugar composition in breast milk, the bacteria could not adhere and form colonies. The HMO mixture was then tested in pregnant mice infected with GBS. The treated mice had a relatively typical level of inflammation, reduced numbers of bacteria in several reproductive tissues, and experienced no instances of preterm births, ruptured membranes or maternal deaths. Taken together, these results demonstrate that HMOs can have antimicrobial effects without additional antibiotics. The researchers say that this work could allow for these sugars to be used as a viable therapeutic option to treat GBS infection and prevent adverse pregnancy outcomes.
The authors acknowledge funding from the National Science Foundation, the National Institutes of Health and the Department of Veterans Affairs.

Everywhere scientists look for microplastics, they’ve found them — food, water, air and some parts of the human body. But examinations of our innermost organs that aren’t directly exposed to the environment are still limited. Now, in a pilot study of people who underwent heart surgery, researchers in ACS’ Environmental Science & Technology report that they have found microplastics in many heart tissues. They also report evidence suggesting that microplastics were unexpectedly introduced during the procedures.
Microplastics are plastic fragments less than 5 millimeters wide, or about the size of a pencil eraser. Research has shown that they can enter the human body through mouths, noses and other body cavities with connections to the outside world. Yet many organs and tissues are fully enclosed inside a person’s body, and scientists lack information on their potential exposure to, and effects from, microplastics. So, Kun Hua, Xiubin Yang and colleagues wanted to investigate whether these particles have entered people’s cardiovascular systems through indirect and direct exposures.
In a pilot experiment, the researchers collected heart tissue samples from 15 people during cardiac surgeries, as well as pre- and post-operation blood specimens from half of the participants. Then the team analyzed the samples with laser direct infrared imaging and identified 20 to 500 micrometer-wide particles made from eight types of plastic, including polyethylene terephthalate, polyvinyl chloride and poly(methyl methacrylate). This technique detected tens to thousands of individual microplastic pieces in most tissue samples, though the amounts and materials varied between participants. All of the blood samples also contained plastic particles, but after surgery their average size decreased, and the particles came from more diverse types of plastics.
Although the study had a small number of participants, the researchers say they have provided preliminary evidence that various microplastics can accumulate and persist in the heart and its innermost tissues. They add that the findings show how invasive medical procedures are an overlooked route of microplastics exposure, providing direct access to the bloodstream and internal tissues. More studies are needed to fully understand the effects of microplastics on a person’s cardiovascular system and their prognosis after heart surgery, the researchers conclude.