Publisher Health

Researchers at La Jolla Institute for Immunology (LJI) have discovered how the immune system can transform into an antibody-making machine capable of neutralizing one of the most elusive viruses out there: HIV.
Researchers once thought that B cells (which make antibodies) spent only weeks perfecting their weaponry against viral threats. Now LJI research shows that a “slow delivery, escalating dose” vaccination strategy can prompt B cells to spend months mutating and evolving their pathogen-fighting antibodies.
This finding, published in Nature, is an important step toward developing effective, long-lasting vaccines against pathogens such as HIV, influenza, malaria, and SARS-CoV-2.
“This shows the immune system can do really extraordinary things if you give it the opportunity — and that in some vaccine contexts, patience really is a virtue,” says study senior author LJI Professor Shane Crotty, Ph.D.
The immune cell evolution inside you
Most pathogens look alien to the immune system. They’re unwelcome visitors covered in unfamiliar proteins. When the body’s dendritic cells see these strange proteins, they signal to “helper” T cells to start training an army.

Duke scientists have identified a previously unknown barrier that separates the bloodstream from smelling cells in the upper airway of mice, likely as a way to protect the brain.
But this barrier also ends up keeping some of the larger molecules of the body’s immune system out, and that may be hindering the effectiveness of vaccines.
It makes sense to have a protective barrier for the olfactory cells lining the nose, because they offer a direct path to the olfactory bulb of the brain, making them effectively extensions of the brain itself, said lead researcher Ashley Moseman, an assistant professor of immunology in the Duke School of Medicine.
However, the new barrier, which his team has dubbed the BOB — the blood-olfactory barrier — also might be keeping vaccines against respiratory viruses from being more effective by preventing those antibodies from reaching the mucous on the surface of the nose, the first barrier a virus encounters.
The team was trying to understand better how the immune system protects the upper respiratory tract by infecting mice with a virus called vesicular stomatitis virus, or VSV, that is known to penetrate to the central nervous system. Once inhaled, VSV readily infects the olfactory sensing cells and rapidly replicates, reaching the olfactory bulb of the brain within a day. Although it can lead to paralysis and death, it is usually cleared by a T cell response.
“VSV is excellent at infecting olfactory sensory neurons, and when it can do that, it will get into the brain,” Moseman said. “Even if you have antibodies in circulation, the blood-olfactory barrier prevents these antibodies from reaching the airway surface, and VSV will get into the brain.”
They wanted to understand better how a prior infection could provide protection against subsequent infection. What they found was that while the BOB prevented circulating antibody protection, it does allow antibody secreting plasma cells to enter olfactory tissues and locally produce neutralizing antibodies. The findings appear Sept. 21 in the journal Immunity.

Chronic, insufficient sleep can negatively affect immune cells, which may lead to inflammatory disorders and cardiovascular disease, according to a new study from the Icahn School of Medicine at Mount Sinai. More specifically, consistently losing an hour and a half of sleep a night potentially increases the risk.
The research, published September 21 in the Journal of Experimental Medicine,is the first to show that sleep alters the structure of DNA inside the immune stem cells that produce white blood cells — also known as immune cells — and this can have a long-lasting impact on inflammation and contribute to inflammatory diseases. Immune cells fight infection, but if the number of these cells gets too high, they overreact and cause inflammation. The study is also the first to show that catching up on sleep doesn’t reverse the effects of sleep disruption.
“This study begins to identify the biological mechanisms that link sleep and immunological health over the long-term. It shows that in humans and mice, disrupted sleep has a profound influence on the programming of immune cells and rate of their production, causing them to lose their protective effects and actually make infections worse — and these changes are long-lasting. This is important because it is yet another key observation that sleep reduces inflammation and, conversely, that sleep interruption increases inflammation,” says lead author Filip Swirski, PhD, Director of the Cardiovascular Research Institute at Icahn Mount Sinai. “This work emphasizes the importance of adults consistently sleeping seven to eight hours a day to help prevent inflammation and disease, especially for those with underlying medical conditions.”
A team of investigators analyzed 14 healthy adults who regularly sleep eight hours a night. First, researchers monitored them sleeping at least eight hours a night for six weeks. They drew their blood and analyzed their immune cells. Then, the same group of adults reduced their sleep time by 90 minutes every night for six weeks, and had their blood and immune cells reanalyzed. At the end of the study researchers compared the blood and cell samples from the full night’s sleep and restricted sleep periods. All participants had significant changes in their immune cells (also known as hematopoietic cells) due to a lack of sleep — there were more of them, and the DNA structure was altered. After six weeks of sleep restriction, they had an increased number of immune cells.
Researchers also analyzed sleep in mouse models. Groups of mice were either allowed to sleep undisturbed, or had sleep fragmentation, where they were awakened throughout the night for 16 weeks. Then, mice with sleep fragmentation went through uninterrupted sleep recovery for ten weeks. Investigators took immune stem cells and immune cells from mice during these undisturbed, fragmented, and sleep recovery phases, analyzed them and compared them at the end of the experiment. Results in mice were consistent with results in humans. They showed that all mice with fragmented sleep had significant changes to their immune stem cells, producing an increased number of immune cells, and also showed evidence of rewiring and reprogramming. A notable finding from the mouse group was that even after sleep recovery, the immune stem cells retained this rewiring structure, and they continued to produce additional white blood cells, making the mice susceptible to inflammation and disease.
“Our findings suggest that sleep recovery is not able to fully reverse the effects of poor-quality sleep. We can detect a molecular imprint of insufficient sleep in immune stem cells, even after weeks of recovery sleep. This molecular imprint can cause the cells to respond in inappropriate ways leading to inflammation and disease,” says co-lead investigator Cameron McAlpine, PhD, Assistant Professor of Medicine (Cardiology) at Icahn Mount Sinai. “It was surprising to find that not all clusters of stem cells responded to insufficient sleep in the same way. There were some stem cell clusters that proliferated and grew in number, while other clusters became smaller. This reduction in overall diversity and aging of the immune stem cell population is an important contributor to inflammatory diseases and cardiovascular disease.”
The National Heart, Lung, and Blood Institute, and the National Center for Advancing Translational Sciences part of the National Institutes of Health, helped fund this study.

The guidance comes as Americans are coping with illness, isolation and loss from the pandemic, as well as other stressors like inflation and rising crime.A panel of medical experts on Tuesday recommended for the first time that doctors screen all adult patients under 65 for anxiety, guidance that highlights the extraordinary stress levels that have plagued the United States since the start of the pandemic.The advisory group, called the U.S. Preventive Services Task Force, said the guidance was intended to help prevent mental health disorders from going undetected and untreated for years or even decades. It made a similar recommendation for children and teenagers earlier this year. The panel, appointed by an arm of the federal Department of Health and Human Services, has been preparing the guidance since before the pandemic. The recommendations come at a time of “critical need,” said Lori Pbert, a clinical psychologist and professor at the University of Massachusetts Chan Medical School, who serves on the task force. Americans have been reporting outsize anxiety levels in response to a confluence of stressors, including inflation and crime rates, fear of illness and loss of loved ones from Covid-19. “It’s a crisis in this country,” Dr. Pbert said. “Our only hope is that our recommendations throw a spotlight on the need to create greater access to mental health care — and urgently.”From August 2020 to February 2021, the percentage of adults with recent symptoms of an anxiety or a depressive disorder increased to 41.5 percent from 36.4 percent, according to one study cited by the task force. The guidance was issued in draft form. The panel will finalize it in the coming months after reviewing public comments. While the panel’s recommendations are not compulsory, they heavily influence the standard of care among primary care physicians across the country.In response to the recommendations, mental health care providers emphasized that screening programs are useful only if they lead patients to effective solutions. At a time when the country is “short on mental health resources on all levels — psychiatrists, psychologists, and therapists — that’s a real concern,” said Dr. Jeffrey Staab, a psychiatrist and chair of the department of psychiatry and psychology at Mayo Clinic in Rochester, Minn.“We can screen lots of people, but if that’s all that happens, it’s a waste of time,” said Dr. Staab, who is not on the task force.Psychiatrists, while pleased with the attention on mental health, also underscored that a standardized screening is only the first step toward a diagnosis, and that providers will need to guard against assuming that a positive screening result indicates a clinical disorder.For many Americans, the screening could simply reveal a temporary period of distress and a need for extra support. “When providers say, ‘You must have a disorder, here, take this,’ we could face an overprescribing problem,” Dr. Staab said. “But the opposite scenario is that we have lots of people suffering who shouldn’t be. Both outcomes are possible.”Rising mental health issues are not unique to the United States. Anxiety and depression increased by 25 percent globally during the first year of the pandemic, according to the World Health Organization, and has only partially improved since. About a quarter of men and about 40 percent of women in the United States face an anxiety disorder in their lifetimes, according to the task force, though much of the data is outdated. Women have nearly double the risk of depression compared with men, studies show, and the recommendation paid special attention to screenings for pregnant and postpartum patients. Physicians typically use questionnaires and scales to survey for mental health disorders. According to the recommendations, positive screening results would lead to additional assessments at the provider’s discretion, depending on underlying health conditions and other life events.Some primary care physicians expressed concern that adding an additional responsibility to their wide-ranging checklist for brief patient appointments is implausible.Dr. Pbert of the task force said that those providers should “do what they already do on a daily basis: Juggle and prioritize.”She also said the task force’s rigorous review of available studies revealed that people of color are often underrepresented in mental health research, which, if not addressed, could contribute to a cycle of inequity.Mental health disparities are rampant in the United States, where Black patients are less likely to be treated for mental health conditions than are white patients, and Black and Hispanic patients are both more frequently misdiagnosed. From 2014 to 2019, the suicide rate among Black Americans increased by 30 percent, data shows.Standardizing screening for all patients could help combat the effects of racism, implicit bias and other systemic issues in the medical field, Dr. Pbert said.The task force panel did not extend its screening recommendations to patients 65 and older. It said there was no clear evidence regarding the effectiveness of screening tools in older adults because anxiety symptoms are similar to normal signs of aging, such as fatigue and generalized pain. The panel also said it lacked evidence on whether depression screening among adults who do not show clear signs of the disorder would ultimately prevent suicides.The task force will accept public comments on the draft recommendation through Oct. 17.

The prevalence, age of onset, and clinical symptoms for virtually all neuropsychiatric disorders differ between men and women. Among the disorders with pronounced sex bias are Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD), where the ratio of males/females diagnosed is approximately 4 to 1. Whether this skewed ratio arises from roles played in brain development by sex-specific DNA sequences or hormones or reflects the way that biological mechanisms and environmental influences elicit behavioral patterns differently in males and females, remains an area of open investigation.
Regardless of origin, altered behavior in these disorders signals a change in the function of key brain circuits wired up during development, refined throughout life, and coordinated through the actions of brain chemicals called neurotransmitters. One vital neurotransmitter that plays a key role in the behaviors altered by both ADHD and ASD is dopamine, whose powerful actions support motor initiation and coordination, motivation, reward and social behavior, as well as attention and higher cognitive function. Although dopamine-sensitive brain circuits engaged in these processes have been under scrutiny for decades, and in the case of ADHD, are the target of medications such as Adderall® and Ritalin®, the intrinsic sex-dependent differences in these pathways that could guide more precise diagnoses and treatments have only recently begun to be elucidated.
To better understand how dopamine levels at brain synapses are managed, neuroscientists from Florida Atlantic University, along with collaborators at the University of North Dakota School of Medicine and Health Sciences, have now added a significant piece to this puzzle by establishing key differences in the molecular dopamine disposal machinery in the brains of male and female mice.
The new research published in the journal Molecular Psychiatry and led by Randy Blakely, Ph.D., professor of biomedical science in FAU’s Schmidt College of Medicine and executive director of the FAU Stiles-Nicholson Brain Institute, provides new insight into how sex determines the mechanisms by which distinct synapses monitor and regulate dopamine signaling. Moreover, the impact the sex differences described is particularly pronounced when the mice express a human genetic variant found in boys with either ADHD or ASD.
“Often, due to assumptions that sex hormone variation will cloud data interpretations, and that use of one sex will cut animal use and costs in half without a loss of key insights, many researchers using animal models to study brain disorders work chiefly with males, even more reasonable when modeling disorders that exhibit male bias,” said Blakely.
In a prior study, looking for genetic changes in dopamine regulatory genes in children with ADHD, Blakely and his team identified a gene variant that alters the function of the dopamine transporter (DAT) in a peculiar way. Normally DAT acts to remove dopamine from synapses, acting like a nanoscale dopamine vacuum cleaner. When the DAT variant was expressed in cells, however, it “ran backward,” spitting out dopamine rather than efficiently removing it. After engineering the variant into the genome of mice, Blakely’s team found changes in behavior and drug responses predicted by this anomalous DAT behavior, with an emphasis on traits linked to pathways related to locomotor activation, habitual behavior and impulsivity. Notably, these studies were performed exclusively with male mutant mice.

Substance abuse among U.S. adolescents is diminishing, except for an uptake in cannabis and vaping use, according to a new study at Columbia University Mailman School of Public Health. The findings show that low social engagement and participation in structured activities seemed to be the overall best predictors of substance abuse avoidance. The results are published online in the journal Substance Use and Misuse.
Examining data from 536,291 adolescents between 1991-2019, a team of researchers suggest that while the reasons for this phenomenon are not entirely clear they appear to correlate to a number of other social factors. These include increased parental monitoring and decreased partying and dating notable among them.
According to lead author, Noah Kreski, MPH, in the Department of Epidemiology at Columbia Mailman School, a number of demographic factors seem to correlate to increased substance abuse even today.
“Substance use prevalence decreases across decades were largest for the groups defined by significant paid employment or high levels of social time, either with low engagement in other activities or lower levels of supervision, though these groups had the highest initial prevalence of each variety of substance use,” says Kreski.
Using data from the National Institute on Drug Abuse (NIDA)’s Monitoring the Future survey the researchers tracked trends in use of cigarettes, alcohol, cannabis, vaping of both nicotine and cannabis, and other substances for school-age student in grades 8 (13-14 years-old), 10 (15-16 years-old) and 12 (17-18 years old), and cross-referenced these habits against demographic factors such as level of social engagement, participation in structured activities, level of adult supervision, and employment. They further analyzed these patterns across race, sex, parental education along with other demographics.
Conversely, substance abuse was higher overall in the highly social and highly engaged groups with less supervision. Time at a paid job was also a significant factor in increasing the chances of trying illicit substances.

People who experience frequent bad dreams in middle age are more likely to be diagnosed with dementia later in life, according to research at the University of Birmingham.
A new study, published in The Lancet journal, eClinicalMedicine, suggests nightmares may become prevalent several years or even decades before the characteristic memory and thinking problems of dementia set in.
Dr Abidemi Otaiku, of the University of Birmingham’s Centre for Human Brain Health, said: “We’ve demonstrated for the first time that distressing dreams, or nightmares, can be linked to dementia risk and cognitive decline among healthy adults in the general population.
“This is important because there are very few risk indicators for dementia that can be identified as early as middle age. While more work needs to be done to confirm these links, we believe bad dreams could be a useful way to identify individuals at high risk of developing dementia, and put in place strategies to slow down the onset of disease.”
In the study, Dr Otaiku examined data from three community-based cohorts in the USA. These included more than 600 adult men and women aged between 35 and 64; and 2,600 adults aged 79 and older. All the participants were dementia-free at the start of the study and followed up for an average of nine years for the younger group and five years for the older participants.
The study started collecting data between 2002 and 2012. Participants completed a range of questionnaires, including the Pittsburgh Sleep Quality Index, which includes a question on how often individuals experienced bad dreams.
This data was analysed using statistical software to find out whether participants with a higher frequency of nightmares were more likely to go on to experience cognitive decline and be diagnosed with dementia.
The research shows that middle-aged people (35-64) who experience bad dreams on a weekly basis are four times more likely to experience cognitive decline over the following decade, while older people were twice as likely to be diagnosed with dementia.
Interestingly, the study found that the associations were much stronger for men than for women. For example, older men experiencing nightmares on a weekly basis were five times more likely to develop dementia than older men reporting no bad dreams. In women, however, the increase in risk was only 41 per cent.
Next steps for the research will include investigating whether nightmares among young people could be associated with future dementia risk, and whether other dream characteristics, such as how often we remember dreams and how vivid they are, could also be used to identify dementia risk. Using electroencephalography (EEG) and magnetic resonance imaging (MRI), the researchers also plan to investigate the biological basis of bad dreams in both healthy people and people with dementia.
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As people with HIV age, their risk of heart attack increases far more if they also have untreated hepatitis C virus, even if their HIV is treated, 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.
Since the introduction of antiretroviral therapies to treat HIV in the late 1990s, the lifespan of people with HIV has increased dramatically. However, even with treatment, studies have found the heart disease risk among people with HIV is at least 50% higher than people without HIV. This new study evaluated if people with HIV who also have hepatitis C — a viral liver infection — have a higher risk of heart attack.
“HIV and hepatitis C coinfection occurs because they share a transmission route — both viruses may be transmitted through blood-to-blood contact,” said Keri N. Althoff, Ph.D., M.P.H., senior author of the study and an associate professor in the department of epidemiology at the Johns Hopkins Bloomberg School of Public Health in Baltimore. “Due in part to the inflammation from the chronic immune activation of two viral infections, we hypothesized that people with HIV and hepatitis C would have a higher risk of heart attack as they aged compared to those with HIV alone.”
Researchers analyzed health information for 23,361 people with HIV (17% female, 49% non-Hispanic white) in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) between 2000 and 2017 and who had initiated antiretroviral treatment for HIV. All were between 40 to 79 years of age when they enrolled in the NA-ACCORD study (median age of 45 years). One in 5 study participants (4,677) were also positive for hepatitis C. During a median follow-up of about 4 years, the researchers compared the occurrence of a heart attack between the HIV-only and the HIV-hepatitis C co-infected groups as a whole, and by each decade of age.
The analysis found: With each decade of increasing age, heart attacks increased 30% in people with HIV alone and 85% in those who were also positive for hepatitis C. The risk of heart attack increased in participants who also had traditional heart disease risk factors such as high blood pressure (more than 3 times), smoking (90%) and Type 2 diabetes (46%). The risk of heart attack was also higher (40%) in participants with certain HIV-related factors such as low levels of CD4 immune cells (200cells/mm3, signaling greater immune dysfunction) and 45% in those who took protease inhibitors (one type of antiretroviral therapy linked to metabolic conditions).”People who are living with HIV or hepatitis C should ask their doctor about treatment options for the viruses and other ways to reduce their cardiovascular disease risk,” said lead study author Raynell Lang, M.D., M.Sc., an assistant professor in the department of medicine and community health sciences at the University of Calgary in Alberta, Canada.
“Several mechanisms may be involved in the increased heart attack risk among co-infected patients. One contributing factor may be the inflammation associated with having two chronic viral infections,” Lang said. “There also may be differences in risk factors for cardiovascular disease and non-medical factors that influence health among people with HIV and hepatitis C that plays a role in the increased risk.”
According to a June 2019 American Heart Association scientific statement, Characteristics, Prevention, and Management of Cardiovascular Disease in People Living With HIV, approximately 75% of people living with HIV are over the age of 45. “Even with effective HIV viral suppression, inflammation and immune dysregulation appear to increase the risk for heart attack, stroke and heart failure.” The statement called for more research on cardiovascular disease prevention, causes and treatment in people with HIV.
“Our findings suggest that HIV and hepatitis C co-infections need more research, which may inform future treatment guidelines and standards of care,” Althoff said.
The study is limited by not having information on additional factors associated with heart attack risk such as diet, exercise or family history of chronic health conditions. Results from this study of people with HIV receiving care in North America may not be generalizable to people with HIV elsewhere. In addition, the study period included time prior to the availability of more advanced hepatitis C treatments.
“Because effective and well-tolerated hepatitis C therapy was not available during several years of our study period, we were unable to evaluate the association of treated hepatitis C infection on cardiovascular risk among people with HIV. This will be an important question to answer in future studies,” Lang said.
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Mosquitoes that spread Zika, dengue and yellow fever are guided toward their victims by a scent from human skin. The exact composition of that scent has not been identified until now.
A UC Riverside-led team discovered that the combination of carbon dioxide plus two chemicals, 2-ketoglutaric and lactic acids, elicits a scent that causes a mosquito to locate and land on its victim. This chemical cocktail also encourages probing, the use of piercing mouthparts to find blood.
This chemical mixture appears to specifically attract female Aedes aegypti mosquitoes, vectors of Zika as well as chikungunya, dengue, and yellow fever viruses. This mosquito originated in Africa, but has spread to tropical and subtropical regions worldwide, including the U.S.
This new research finding, and how the team discovered it, is detailed in the journal Scientific Reports. “Though others have identified compounds that attract mosquitoes, many of them don’t elicit a strong, rapid effect. This one does,” said Ring Cardé, UCR entomologist.
Mosquitoes use a variety of cues to locate their victims, including carbon dioxide, sight, temperature, and humidity. However, Cardé’s recent research shows skin odors are even more important for pinpointing a biting site.
“We demonstrated that mosquitoes land on visually indistinct targets imbued with these two odors, and these targets aren’t associated with heat or moisture,” Cardé said. “That leaves skin odor as the key guiding factor.”
Given the significance of odor in helping mosquitoes successfully feed on humans, Cardé wanted to discover the exact chemicals that make our scent so potent for the insects. Part of the equation, lactic acid, was identified as one chemical element in the odor cocktail as long ago as 1968.

It may be the most baffling quirk of COVID: What manifests as minor, flu-like symptoms in some individuals spirals into severe disease, disability, and even death in others. A new paper published in Nature may explain the genetic underpinnings of this dichotomy.
The researchers demonstrated that mice with gene variants previously linked to Alzheimer’s disease were at greater risk of dying when infected with COVID. And a retrospective analysis suggests that patients with those same gene variants were more likely to have died of COVID throughout the pandemic. Because three percent of the world population possesses these gene variants, the findings may have implications for hundreds of millions of individuals globally.
“It is clear that age, sex, and certain preconditions such as diabetes increase the risk of detrimental outcomes, but these factors don’t fully explain the spectrum of COVID outcomes,” says Sohail Tavazoie, the Leon Hess Professor at The Rockefeller University. “This is the first time that we’ve seen such a common genetic variant associated with COVID mortality.”
A closer look at APOE
In previous work, Tavazoie’s lab studied a gene called APOE that plays a role in cancer metastasis. After demonstrating that the gene suppresses the spread of melanoma and regulates anti-tumor immune responses, he and his team began looking at its different forms, or alleles, more closely. Most people have a form called APOE3, but 40 percent of the population carries at least one copy of the APOE2 or APOE4 variant. Individuals with APOE2 or APOE4 produce proteins that differ from APOE3 protein by one or two amino acids.
One or two amino acids make a difference. Individuals with APOE4 are at greater risk of developing Alzheimer’s and atherosclerosis, and Tavazoie and Benjamin Ostendorf, a postdoctoral fellow in his lab, have demonstrated that APOE4 and APOE2 impact the immune response against melanoma. As the pandemic progressed, Tavazoie and Ostendorf began to wonder whether APOE variants might impact COVID outcomes, too. “We had looked only at non-infectious diseases,” he says. “But what if APOE variants also made people vulnerable to an infectious agent, like SARS-CoV-2? Could they cause different immune responses against a virus?”
To find out, Tavazoie and colleagues first exposed more than 300 mice engineered to carry human APOE to a mouse-adapted version of SARS-CoV-2 produced by colleagues Hans-Heinrich Hoffmann and Charles M. Rice. They found that mice with APOE4 and APOE2 were more likely to die than those with the more common APOE3 allele. “The results were striking,” says Ostendorf, lead author on the study. “A difference in just one or two amino acids in the APOE gene was sufficient to cause major differences in the survival of mice exhibiting COVID.”