Publisher Health

A National Institutes of Health-supported study found that high-density lipoprotein (HDL) cholesterol, often called the “good cholesterol,” may not be as effective as scientists once believed in uniformly predicting cardiovascular disease risk among adults of different racial and ethnic backgrounds.
The research, which published in the Journal of the American College of Cardiology, found that while low levels of HDL cholesterol predicted an increased risk of heart attacks or related deaths for white adults — a long-accepted association — the same was not true for Black adults. Additionally, higher HDL cholesterol levels were not associated with reduced cardiovascular disease risk for either group.
“The goal was to understand this long-established link that labels HDL as the beneficial cholesterol, and if that’s true for all ethnicities,” said Nathalie Pamir, Ph.D., a senior author of the study and an associate professor of medicine within the Knight Cardiovascular Institute at Oregon Health & Science University, Portland. “It’s been well accepted that low HDL cholesterol levels are detrimental, regardless of race. Our research tested those assumptions.”
To do that, Pamir and her colleagues reviewed data from 23,901 United States adults who participated in the Reasons for Geographic and Racial Differences in Stroke Study (REGARDS). Previous studies that shaped perceptions about “good” cholesterol levels and heart health were conducted in the 1970s through research with a majority of white adult study participants. For the current study, researchers were able to look at how cholesterol levels from Black and white middle-aged adults without heart disease who lived throughout the country overlapped with future cardiovascular events.
Study participants enrolled in REGARDS between 2003-2007 and researchers analyzed information collected throughout a 10- to 11-year period. Black and white study participants shared similar characteristics, such as age, cholesterol levels, and underlying risk factors for heart disease, including having diabetes, high blood pressure, or smoking. During this time, 664 Black adults and 951 white adults experienced a heart attack or heart attack-related death. Adults with increased levels of LDL cholesterol and triglycerides had modestly increased risks for cardiovascular disease, which aligned with findings from previous research.
However, the study was the first to find that lower HDL cholesterol levels only predicted increased cardiovascular disease risk for white adults. It also expands on findings from other studies showing that high HDL cholesterol levels are not always associated with reduced cardiovascular events. The REGARDS analysis was the largest U.S. study to show that this was true for both Black and white adults, suggesting that higher than optimal amounts of “good” cholesterol may not provide cardiovascular benefits for either group.

Intestinal bacteria composition is crucial to driving the recovery of neutrophils counts in the blood of mice following treatments such as stem cell transplants or chemotherapy.
White blood cells, or granulocytes, are cells that are part of the innate immune system. The most common type of granulocyte is the neutrophil, a phagocyte that destroys microbes in the body. Low neutrophil counts in the blood is called neutropenia; this condition is commonly seen in cases of leukemia or following chemotherapy. It is known that neutropenia induces granulopoiesis, the process formation of granulocytes. However, the exact mechanisms by which neutropenia drives granulopoiesis are not fully understood.
A team of researchers led by Associate Professor Daigo Hashimoto and Professor Takanori Teshima at Hokkaido University’s Faculty of Medicine have discovered that the gut microbiome plays a critical role in driving granulopoiesis in mice models. Their findings were published in the journal Proceedings of the National Academy of Sciences.
The process of increasing granulopoiesis above a homeostatic level can be divided into emergency granulopoiesis, driven by the presence of bacteria, and reactive granulopoiesis, where granulopoiesis is increased in the absence of active microbial infections. It was known that reactive granulopoiesis occurs after neutropenia caused by hematopoietic stem cell transplantation (SCT) or cancer chemotherapy. The team wanted to understand the mechanisms by which neutropenia triggered reactive granulopoiesis in these two scenarios.
The team induced prolonged neutropenia in mice models, and observed the levels of cytokines, cell signalling molecules, known to be associated with granulopoiesis. They found that two cytokines were significantly elevated: the granulocyte-colony stimulating factor (G-CSF) and interleukin 17A (IL-17A). They showed that IL-17A was critical for neutrophil recovery. They confirmed that T cells are the primary source of IL-17A.
They were interested in examining if the gut microbiome influenced granulopoiesis, building on other research that suggested the gut microbiome and bone marrow haematopoiesis could affect each other. They found that the gut microbiome does upregulate reactive granulopoiesis via the IL-17A secreted by T cells, and also found that prolonged neutropenia alters the gut microbiome. They determined that it was this change in microbiome composition that enhanced reactive granulopoiesis.
This study demonstrated that the changes in intestinal microbiome induced by neutropenia stimulates reactive granulopoiesis in the bone marrow via IL-17A secreted by T cells, promoting neutrophil recovery. Future work will focus on clinical trials to test if this crosstalk is found in humans; other avenues include the development of antibiotic formulations that leave granulopoiesis-supporting bacteria intact.
Story Source:
Materials provided by Hokkaido University. Note: Content may be edited for style and length.

Does the history of our languages match the history of our genes? A team of scientists at the University of Zurich and the Max-Planck-Institute have revealed a large number of matches — but also widespread mismatches in around 20 percent of cases, including in Malta, Hungary and Namibia.
More than 7,000 languages are spoken in the world. This linguistic diversity is passed on from one generation to the next, similarly to biological traits. But have language and genes evolved in parallel over the past few thousand years, as Charles Darwin originally thought? An interdisciplinary team at the University of Zurich together with the Max Planck Institute for Evolutionary Anthropology in Leipzig (Germany) has now examined this question at a global level. The researchers put together a global database linking linguistic and genetic data entitled GeLaTo (Genes and Languages Together), which contains genetic information from some 4,000 individuals speaking 295 languages and representing 397 genetic populations.
One in five gene-language links point to language shifts
In their study, the researchers examined the extent to which the linguistic and genetic histories of populations coincided. People who speak related languages tend to also be genetically related, but this isn’t always the case. “We focused on cases where the biological and linguistic patterns differed and investigated how often and where these mismatches occur,” says Chiara Barbieri, UZH geneticist who led the study and initiated it together with colleagues when she was a postdoc at the Max-Planck-Institute.
The researchers found that about every fifth gene-language relation is a mismatch, and they occurr worldwide. These mismatches can provide insights into the history of human evolution. “Once we know where such language shifts happened, we can better reconstruct how languages and populations spread across the world,” says Balthasar Bickel, director of the National Center of Competence in Research (NCCR) Evolving Language, who co-supervised the study.
Switching to the local lingo
Most mismatches result from populations shifting to the language of a neighboring population that is genetically different. Some peoples on the tropical eastern slopes of the Andes speak a Quechua idiom that is typically spoken by groups with a different genetic profile who live at higher altitudes. The Damara people in Namibia, who are genetically related to the Bantu, communicate using a Khoe language that is spoken by genetically distant groups in the same area. And some hunter-gatherers who live in Central Africa speak predominantly Bantu languages without a strong genetic relatedness to the neighboring Bantu populations.
In addition, there are cases where migrants have picked up the local language of their new homes. The Jewish population in Georgia, for example, adopted a South Caucasian language, while the Cochin Jews in India speak a Dravidian language. The case of Malta reflects its history as an island between two continents: while the Maltese are closely related to the people of Sicily, they speak an Afroasiatic language that is influenced by various Turkish and Indo-European languages.
Preserving their linguistic identity
“It appears that giving up your language isn’t that difficult, also for practical reasons,” says the last author Kentaro Shimizu, director of the URPP Evolution in Action: From Genomes to Ecosystems. However, it’s more rare for people to preserve their original linguistic identity despite genetic assimilation with their neighbors. “Hungarian people, for example, are genetically similar to their neighbors, but their language is related to languages spoken in Siberia.”
This makes Hungarian speakers stand out from among the rest of Europe and parts of Asia, where most people speak Indo-European languages, such as French, German, Hindi, Farsi, Greek and many others. Indo-European has not only been extensively studied, but also scores particularly high in terms of genetic and linguistic congruence. “This might have given the impression that gene-language matches are the norm, but our study shows that this isn’t the case,” concludes Chiara Barbieri, who adds that it is important to include genetic and linguistic data from populations all over the world to understand language evolution.
Story Source:
Materials provided by University of Zurich. Note: Content may be edited for style and length.

Infectious diseases expert George Thompson has been studying and treating fungal diseases for over two decades. He monitors their spread, symptoms and relative risks. Lately, he has been more concerned about a rising threat: the spread of disease-causing fungi outside of their traditional hot spots.
In a commentary published in Annals of Internal Medicine, Thompson and his co-author from the Mycotic Diseases Branch at the Centers for Disease Control and Prevention Tom Chiller raised the alarm. They noted the expanding presence and emerging risks from three endemic fungal diseases: histoplasmosis, blastomycosis and coccidioidomycosis (Valley fever).
“These three fungal diseases usually inhabit specific U.S. regions conducive to their survival,” said Thompson. He is a professor at the UC Davis School of Medicine in the Department of Internal Medicine, Division of Infectious Diseases, and the Department of Medical Microbiology and Immunology. “Recently, we are finding more cases of these diseases outside their known areas, taking clinicians and patients by surprise.”
Fungal infections are an emerging global threat
Fungi are microorganisms found abundantly in nature. They include yeasts, molds, mushrooms and more. While most fungi are harmless to humans, some can cause diseases (known as mycoses) that could wreak havoc on patients and the health system.
Recently, the World Health Organization (WHO) released its fungal priority pathogens list, identifying the most concerning fungi that can cause infections for which drug resistance or other treatment challenges exist. These pathogens are projected to lead to even more problems over the next decade.

Despite monkeypox fading from public attention, scientists are still learning how it spreads — including without sexual contact or any symptoms.In the monkeypox outbreak that unspooled this summer in the United States and dozens of other countries, men who have sex with men were the most at risk. But thousands of women were also infected, and many more cases were probably missed, according to the first ever study of women and nonbinary people who had contracted the disease.As in men, sexual contact was most likely to be the source of infection among transgender women, accounting for 89 percent of cases, according to the case series, published on Thursday in the journal Lancet. But among cisgender women and nonbinary individuals who were assigned female at birth, only 61 percent of cases could be connected to sexual contact.Nearly one-quarter of cisgender women in the study might have been infected without sexual interaction with an infected person, said Dr. Chloe Orkin, a physician and researcher at Queen Mary University of London. The women were thought to have been infected through exposure at their jobs or homes or through other types of close contact.“The lesson here is that everybody needs to know about this,” Dr. Orkin said. While it’s appropriate that public health messages have mostly been directed at men who have sex with men, she added, “it’s important to recognize this is not the only group.”After several months of rapidly escalating case numbers, the monkeypox outbreak in the United States has slowed, thanks in part to a vaccination campaign and changes in the behavior of many high-risk individuals. Since May, there have been just over 29,000 cases in the United States, but only about a thousand cases have been diagnosed in the last month.Yet as the disease fades from public attention, scientists are just beginning to understand when and how it spreads and who is at risk.In the new study, Dr. Orkin and her colleagues found genetic material from the monkeypox virus in all 14 of the vaginal swabs they tested, suggesting that the virus can be transmitted through genital secretions. Studies in men have similarly found the virus in seminal fluid.Still, public health authorities have hesitated to call monkeypox a sexually transmitted infection, arguing that the virus can spread through close physical contact of any kind.But some experts disagree: The fact that monkeypox can be transmitted in other ways should not preclude its classification as a sexually transmitted disease, because other diseases like herpes and syphilis can also spread through nonsexual close contact, some have said.Last month, New York State added monkeypox to its list of sexually transmitted infections, but the Centers for Disease Control and Prevention has not made that change. The agency will leave that categorization up to individual states, said Dr. Demetre Daskalakis, deputy coordinator of the White House’s monkeypox response. But it’s clear that sexual behavior drives cases, he said.“If you took sex away, would we have had a monkeypox outbreak? Probably not,” he added. Even if the primary reason for the spread is skin-to-skin contact during sexual activity, “it’s definitely a sexually associated transmission.”Morgan Verrett, a Renegade Bio Lab Assistant, processed monkeypox samples collected in San Francisco. Mike Kai Chen for The New York TimesThis year, Dr. Orkin led an international collaboration to characterize monkeypox symptoms in 500 patients. The findings led Britain, the United States and other countries to refine their case definitions of the disease.And last month, the U.K. Health Security Agency published a study suggesting that between about 40 percent and 60 percent of monkeypox transmission may occur before infected people develop symptoms.This makes sense intuitively because once patients develop the painful blisters, they would be unlikely to have sex, noted Tom Ward, an infectious disease modeler for the agency. Some small percentage of infected people may never develop symptoms, he said.Tracing contacts in a monkeypox outbreak is extremely challenging because of the sensitive and often anonymous nature of spread; there are no tests that can detect monkeypox before the characteristic skin rash appears.“What it essentially highlights is that we still need a lot of research into the nature of asymptomatic and pre-symptomatic transmission of monkeypox,” Dr. Ward said.Some people may have mild, generic symptoms like a sore throat before developing the rash.Those individuals should stay home to protect others, Dr. Daskalakis said. But ultimately, he said, the possibility of pre-symptomatic spread doesn’t change the public health message to people at risk: immunization against monkeypox.“Probably the strongest guidance is that if there is past history that would make you think that you’re at risk for monkeypox, it’s important to get vaccinated, and if there’s a potential for future risk, it’s important to get vaccinated,” he added.The new study is the first to describe monkeypox in transgender or nonbinary people, who often have little access to quality health care and are rarely included in research studies.“It’s very, very important that we report on both sex and gender differences, because both are important, and in some cases, they intersect,” Dr. Orkin said.In the study, researchers from 15 countries contributed clinical information from 69 cisgender women, 62 transgender women and five nonbinary individuals who were diagnosed with monkeypox between May 11 and Oct. 4. About 45 percent of the women were Latino, 29 percent were white and 21 percent were Black.A makeshift monkeypox vaccination clinic in Manhattan this summer.Andrew Seng for The New York TimesMore than half the patients in the study had sores in their anus, genitals, mouth or eyes. But some women — especially cisgender women — were initially misdiagnosed with other sexually transmitted infections.Experts had anticipated that monkeypox “would have probably a slightly different pattern of transmission depending on social behaviors and norms within certain groups,” said Dr. Abraar Karan, an infectious diseases physician at Stanford University.The new study supported that inference. In contrast with male monkeypox patients who have sex with men, only 7 percent of the patients in the study reported having attended a Pride event or other similar gatherings. While the transgender women in the study had had about 10 partners on average over the previous month, the cisgender women had one, and 7 percent of the cisgender women said they had no sexual partners in the previous month.“So the driver was not the same,” Dr. Karan said.Many of the transgender women in the study had other risk factors for monkeypox, including undiagnosed and untreated H.I.V., homelessness and injection drug use. Half of the transgender women in the study had H.I.V. compared with 8 percent of the cisgender women, and more than half of the transgender women were engaged in commercial sex work compared with 3 percent of cisgender women.“Even though the absolute number of people who are trans and engaged in sex work may not be very large, the extremely high prevalence of H.I.V. and now monkeypox and other sexually transmitted infections means that public health agencies need to be thinking of ways to do outreach in this population,” said Dr. Jay Varma, director of the Cornell Center for Pandemic Prevention and Response.While many of the transgender women sought care at sexual health clinics, the cisgender women in the study went to primary care providers or to emergency departments, where doctors were more likely to be unfamiliar with monkeypox symptoms. About one in three cisgender women were diagnosed late or with another disease; some were probably never diagnosed.“It’s very likely that infections have been missed and not picked up at all,” Dr. Orkin said.About one in four of the cisgender women in the study lived with children, but the doctors identified only two cases of monkeypox among them. The C.D.C.’s observations jibe with that finding.But Dr. Karan cautioned that cases in children might be under reported because of the stigma associated with monkeypox. More studies are needed to understand how symptoms may vary in different populations, particularly in countries where the virus has caused outbreaks for years, he said.

Tick bites transmit Lyme disease. But even knowing where these ticks live doesn’t necessarily mean you can predict the disease in humans. It’s only one part of a broader picture which includes human behavior and the habits of the parasite’s carriers.
Researchers at UC Santa Barbara have discovered that the ecology of the small mammals upon which ticks feed can explain rates of human Lyme disease, at least in California. As a result, scientists and health officials may be able to predict future disease risk by studying the response of these animals, and their tick parasites, to changing climate and land use. The findings appear in the journal Environmental Research Letters.
“This study is unique because it tries to quantify the links connecting climate to mammals to ticks to humans, which requires different types of data, research techniques and academic backgrounds,” said co-author Sam Sambado, a doctoral student in the Department of Ecology, Evolution, and Marine Biology.
Lyme disease is primarily caused by the bacterium Borrelia burgdorferi by way of tick bites. However, the western blacklegged tick isn’t born with the bacterium. It can only contract the pathogen by feeding on an infected host, which serves as a reservoir for the microbe.
The ecology of the tick’s hosts should affect the distribution of the disease in humans, but the connection isn’t always straightforward. “It’s challenging to link the ecology to the epidemiology — or where people get sick — because humans change their behavior based on risk,” said first author Andy MacDonald, an assistant professor at the Bren School of Environmental Science & Management. Where people go, how they interact with the landscape, and whether they take precautions against tick bites all influence where people contract Lyme disease.
The researchers had two questions in mind. First, what environmental factors affect the infection rate in tick populations? Second, can this knowledge be used to predict human infections?

An international team of scientists investigating transmission of a deadly drug resistant bacteria that rivals MRSA, has found that whilst the bugs are found in livestock, pets and the wider environment, they are rarely transmitted to humans through this route.
The researchers, led by Professor Ed Feil from the Milner Centre for Evolution at the University of Bath, investigated the prevalence of Klebsiella, a family of bacterial species that lives harmlessly in the intestines, but can be dangerous if it spreads to other parts of the body.
Klebsiella pneumoniae is the most well-known species in this family, which can cause pneumonia, meningitis, urinary tract infections and infections in the bloodstream.
These bacteria are now highly resistant to antibiotics, with some strains even resistant to carbapenems, one of the so-called “last resort” class of antibiotics which is only used when no other antibiotic treatment works.
Klebsiella has overtaken MRSA as a health problem in the UK, with rates steadily increasing. The WHO has recognised the bacteria as a critical priority healthcare associated pathogen.
As well as being found in hospitals, the microbe has also previously been detected in the environment, including livestock and wastewater, but until now it wasn’t clear whether the bacteria were passed between clinical and non-clinical environments.

Scientists looking to understand the fundamental brain mechanisms of autism spectrum disorder have found that a gene mutation known to be associated with the disorder causes an overstimulation of brain cells far greater than that seen in neuronal cells without the mutation.
The Rutgers-led study, spanning seven years, employed some of the most advanced approaches available in the scientific toolbox, including growing human brain cells from stem cells and transplanting them into mouse brains.
The work illustrates the potential of a new approach to studying brain disorders, scientists said.
Describing the study in the journal, Molecular Psychiatry, researchers reported a mutation — R451C in the gene Neurologin-3, known to cause autism in humans — was found to provoke a higher level of communication among a network of transplanted human brain cells in mouse brains. This overexcitation, quantified in experiments by the scientists, manifests itself as a burst of electrical activity more than double the level seen in brain cells without the mutation.
“We were surprised to find an enhancement, not a deficit,” said Zhiping Pang, an associate professor in the Department of Neuroscience and Cell Biology in the Child Health Institute of New Jersey at Rutgers Robert Wood Johnson Medical School and the senior author on the study. “This gain-of-function in those specific cells, revealed by our study, causes an imbalance among the brain’s neuronal network, disrupting the normal information flow.”
The interconnected mesh of cells that constitutes the human brain contains specialized “excitatory” cells that stimulate electrical activity, balanced by “inhibitory” brain cells that curtail electrical pulses, Pang said. The scientists found the oversized burst of electrical activity caused by the mutation threw the mouse brains out of kilter.

New research from the University of California, Irvine, suggests aging is an important component of retinal ganglion cell death in glaucoma, and that novel pathways can be targeted when designing new treatments for glaucoma patients.
The study, titled, “Stress induced aging in mouse eye,” was published today in Aging Cell. Along with her colleagues, Dorota Skowronska Krawczyk, PhD, assistant professor in the Departments of Physiology & Biophysics and Ophthalmology and the faculty of the Center for Translational Vision Research at the UCI School of Medicine, describes the transcriptional and epigenetic changes happening in aging retina. The team shows how stress, such as intraocular pressure (IOP) elevation in the eye, causes retinal tissue to undergo epigenetic and transcriptional changes similar to natural aging. And, how in young retinal tissue, repetitive stress induces features of accelerated aging including the accelerated epigenetic age.
Aging is a universal process that affects all cells in an organism. In the eye, it is a major risk factor for a group of neuropathies called glaucoma. Because of the increase in aging populations worldwide, current estimates show that the number of people with glaucoma (aged 40-80) will increase to over 110 million in 2040.
“Our work emphasizes the importance of early diagnosis and prevention as well as age-specific management of age-related diseases, including glaucoma,” said Skowronska-Krawczyk. “The epigenetic changes we observed suggest that changes on the chromatin level are acquired in an accumulative way, following several instances of stress. This provides us with a window of opportunity for the prevention of vision loss, if and when the disease is recognized early.”
In humans, IOP has a circadian rhythm. In healthy individuals, it oscillates typically in the 12-21 mmHg range and tends to be highest in approximately two thirds of individuals during the nocturnal period. Due to IOP fluctuations, a single IOP measurement is often insufficient to characterize the real pathology and risk of disease progression in glaucoma patients. Long-term IOP fluctuation has been reported to be a strong predictor for glaucoma progression. This new study suggests that the cumulative impact of the fluctuations of IOP is directly responsible for the aging of the tissue.
“Our work shows that even moderate hydrostatic IOP elevation results in retinal ganglion cell loss and corresponding visual defects when performed on aged animals,” said Skowronska-Krawczyk. “We are continuing to work to understand the mechanism of accumulative changes in aging in order to find potential targets for therapeutics. We are also testing different approaches to prevent the accelerated aging process resulting from stress.”
Researchers now have a new tool to estimate the impact of stress and treatment on the aging status of retinal tissue, which has made these new discoveries possible. In collaboration with the Clock Foundation and Steve Horvath, PhD, from Altos Labs, who pioneered the development of epigenetic clocks that can measure age based on methylation changes in the DNA of tissues, it was possible for researchers to show that repetitive, mild IOP elevation can accelerate epigenetic age of the tissues.
“In addition to measuring vision decline and some structural changes due to stress and potential treatment, we can now measure the epigenetic age of retinal tissue and use it to find the optimal strategy to prevent vision loss in aging,” said Skowronska-Krawczyk.
This research was funded in part by the National Institutes of Health, the Foundation for Polish Science and the European Union under the European Regional Development Fund. Authors would like to acknowledge support of the Research to Prevent Blindness Foundation for Department of Ophthalmology at UCI.
Story Source:
Materials provided by University of California – Irvine. Note: Content may be edited for style and length.

Sitting atop the kidneys, the adrenal gland plays a pivotal role in maintaining a healthy body. Responding to signals from the brain, the gland secretes hormones that support critical functions like blood pressure, metabolism, and fertility.
People with adrenal gland disorders, such as primary adrenal insufficiency, in which the gland does not release sufficient hormones, can suffer fatigue, dangerously low blood pressure, coma, and even death if untreated. No cure for primary adrenal insufficiency exists, and the lifelong hormone-replacement therapy used to treat it carries significant side effects.
A preferable alternative would be a regenerative medicine approach, regrowing a functional adrenal gland capable of synthesizing hormones and appropriately releasing them in tune with the brain’s feedback. With a new study in the journal Developmental Cell, researchers from the University of Pennsylvania School of Veterinary Medicine coaxed stem cells in a petri dish to divide, mature, and take on some of the functions of a human fetal adrenal gland, bringing that goal one step closer.
“This is a proof-of-principle that we can create a system grown in a dish that functions nearly identically to a human adrenal gland in the early stages of development,” says Kotaro Sasaki, senior author and an assistant professor at Penn Vet. “A platform like this could be used to better understand the genetics of adrenal insufficiency and even for drug screening to identify better therapies for people with these disorders.”
Sasaki says his team’s aim was to use human inducible pluripotent stem cells (iPSCs), which can give rise to a myriad of different cell types, to mimic the stages of normal human adrenal development. During this process, the cells would get directed to take on the characteristics of the adrenal gland.
To begin, the researchers used what’s known as an “organoid culture” system, in which cells grow first as a floating aggregate for three weeks, then on a membrane exposed to air on one side, promoting better survival and allowing them to proliferate in three dimensions. Utilizing a carefully selected growth medium, they prompted the iPSCs to elicit an intermediate tissue type in the adrenal development process, the posterior intermediate mesoderm (PIM).