Publisher Health

Why do some people with cold sores around their lips experience painful lesions, while others have no symptoms at all, yet still spread the virus? A new study conducted at Penn State finds that these differences could be due to variations in the way certain strains of herpes simplex (HSV-1) — the virus that causes cold sores, as well as genital herpes — activate gene expression in neurons.
“HSV-1 occurs in more than half the global population,” said Moriah Szpara, associate professor of biology and biochemistry and molecular biology. “Not only does it cause recurrent problems, such as cold sores and genital herpes, but recent research has implicated chronic HSV-1 infection with the development of disease later in life, including neurodegenerative diseases like Alzheimer’s.”
Szpara explained that the HSV-1 lifecycle begins upon contact with mucosal surfaces, where it invades skin cells, replicates, and can induce local lesion formation. The virus also enters local nerve endings in the skin, and transits into neurons in the nervous system. There the virus can lie dormant until it reactivates on future occasions. Neuronal damage and host immune responses triggered by viral reactivations are thought to contribute to long-term neurodegeneration.
“Since every person carries a subtly different version of HSV-1, this might explain some of the variation in human responses to infection; for example, why people have different triggers for their outbreaks or why some people experience more painful sores. Differences in the frequency of viral outbreaks, or in virus-induced gene expression patterns, might also affect the different rates at which people with chronic infections go on to develop neurodegenerative diseases.”
To investigate the causes of this variation in responses, Szpara and her colleagues infected human neuronal cells with one of three HSV-1 strains that are known to differ in their ability to cause disease in the nervous system. Next, they used deep sequencing to identify and quantify the transcriptomes — the entire set of messenger RNAs (mRNAs) made in a cell at any given time — of the neurons during infection by HSV-1.
According to Szpara, when a neuronal cell is infected with HSV-1, the resulting transcriptome includes the whole collection of mRNAs produced by both the human neuron and the HSV-1 virus. By looking at the timing and amount of mRNAs expressed during infection, scientists can gain insights on the proteins that will soon be produced from those mRNAs. It is the viral proteins and new viral progeny produced during infection that ultimately lead to health problems.

A pilot human clinical trial conducted by researchers at Baylor College of Medicine reveals that supplementation with GlyNAC — a combination of glycine and N-acetylcysteine as precursors of the natural antioxidant glutathione — could improve many age-associated defects in older humans to improve muscle strength and cognition, and promote healthy aging.
Published in the journal Clinical and Translational Medicine, the results of this study show that older humans taking GlyNAC for 24 weeks saw improvements in many characteristic defects of aging, including glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, body fat, genomic toxicity, muscle strength, gait speed, exercise capacity and cognitive function. The benefits declined after stopping supplementation for 12 weeks. GlyNAC supplementation was well tolerated during the study period.
“There is limited understanding as to why these defects occur in older humans, and effective interventions to reverse these defects are currently limited or lacking,” said corresponding author endocrinologist Dr. Rajagopal Sekhar, associate professor of medicine in the Section of Endocrinology, Diabetes and Metabolism at Baylor.
For the last 20 years, Sekhar and his team have been studying natural aging in older humans and aged mice. Their work brings mitochondria, known as the batteries of the cell, as well as free radicals and glutathione to the table in discussions about why we age.
Mitochondrial dysfunction and aging
Mitochondria generate energy needed for supporting cellular functions by burning fat and sugar from foods, therefore mitochondrial health is critically important for life. Sekhar believes that improving the health of malfunctioning mitochondria in aging is the key.

Use of vouchers and coupons offered by pharmaceutical companies to defray patients’ out-of-pocket drug costs is concentrated among a small number of drugs. While these offsets significantly reduce patient costs, they are not targeted to patients who most need the price reduction, according to a study from researchers at the Johns Hopkins Bloomberg School of Public Health.
The researchers, in what is thought to be the largest study of its kind to date, analyzed tens of millions of pharmacy transactions by more than 600,000 people in the U.S. during 2017-19, in order to get a better sense of how vouchers and other point-of-sale copayment “offsets” are used. These coupons and vouchers come in many forms — some are offered online directly to customers, others by pharmacy chains, some as “drug discount cards,” and through smart phone apps.
Their study found that about half of the more than four million offsets included in the analysis were provided by pharmaceutical companies, and half by pharmacies or pharmacy benefit managers (PBMs), companies that manage prescription drugs plans for large employers, health insurers and the Medicare program. In each of these categories, offsets were concentrated among a relatively small number of drugs. The researchers found no evidence that offsets differed much depending on the local average income, ethnic/racial makeup, or level of insurance coverage.
The study appears online in JAMA Internal Medicine on March 29.
The disease categories for which offsets for branded drugs were most common included diabetes, lung disease, and cardiovascular disease, and there was a clear concentration among a relatively small number of drugs: 80 percent of manufacturer-sponsored offsets applied to just 164 drugs, out of a total of 2,661 drugs that received at least one manufacturer-sponsored offset. Similarly, 80 percent of pharmacy/PBM-sponsored offsets were for just 156 out of a total of 3,175 drugs receiving pharmacy/PBM offsets.
“The most significant finding was that these offsets are not being targeted to people who likely need them the most — for the pharmaceutical company-sponsored offsets, the goal may be mainly to maintain market share,” says study lead author, Aditi Sen, PhD, assistant professor in the Department of Health Policy and Management at the Bloomberg School. “Understanding different offset types and which patients use them is important for designing policy.”
Coupons, vouchers, and other copay offsets are widely seen as responses to the unusually high prices of prescription drugs in the U.S. Pharmaceutical companies want to make it easier for patients to buy their branded drugs rather than generic competitors, whereas PBMs typically want to steer patients away from the more expensive branded drugs to lower-cost substitutes.

The recommendations are clear: physical activity is good for mental health. But it also depends on how varied it is. That’s what a new study by researchers at the University of Basel shows, pointing to one of the reasons why well-being suffers during the pandemic.
A walk in the morning, a jog in the evening or even just going out to buy groceries: activity helps the psyche. Many are trying to stay active during the pandemic despite mandatory home office and limited leisure activities. Others find that they are moving significantly less than before the pandemic because previous everyday activities are off-limits due to measures taken against the spread of Covid-19.
Against this backdrop, a study led by Professor Andrew Gloster of the University of Basel provides an indication of what impact restricted movement patterns might have. The results have been published in the journal BMC Psychiatry.
That exercise promotes not only physical but also mental health is known from various studies. However, these mostly focused on the influence of deliberate exercise programs. “In contrast, little was known about whether everyday, naturally chosen movement patterns also influence mental health,” Gloster explains.
To investigate this, he and researchers at the University Psychiatric Clinics in Basel collected GPS data from 106 patients with mental disorders who agreed to participate. For this purpose, the study participants were given extra smartphones that they carried with them for a week. This allowed the researchers to track their movements without interfering with the patients’ daily routine. The research team then compared the movement data with surveys of the participants’ well-being and symptoms of their mental illness.
The results showed that the more people moved and the more varied their movements, the greater their sense of well-being. However, no influence on the symptoms could be determined. “Our results suggest that activity alone is not enough to reduce symptoms of mental disorders, but can at least improve subjective well-being,” Gloster elaborates.
“Although the data were collected before the pandemic, the results are also relevant in light of the limitations during the coronavirus crisis,” he adds. Because many social and recreational activities were discontinued during that time, many people’s physical activity patterns also likely became more monotonous. Various studies by research groups at the University of Basel have been able to show that the pandemic took a toll on the psyche of the population. The results of the team led by Gloster suggest that the restricted movement patterns could also play a role in this.
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Materials provided by University of Basel. Note: Content may be edited for style and length.

In order to develop more effective drugs against a range of cancers, researchers have been investigating the molecular structure of many diseased-linked enzymes in the body. An intriguing case in point is Taspase 1, a type of enzyme known as a protease. The primary duty of proteases is to break down proteins into smaller peptide snippets or single amino acids.
Taspase 1 appears to play a vital role in a range of physiological processes, including cell metabolism, proliferation, migration and termination. The normal functioning of Taspase 1 can go awry however, leading to a range of diseases, including leukemia, colon and breast cancers, as well as glioblastoma, a particularly lethal and incurable malignancy in the brain.
Because Taspase 1 dysregulation is increasingly implicated in the genesis and metastasis of various cancers, it has become an attractive candidate for drug development. But before this can happen, researchers will need a highly detailed blueprint of the structure of this protease.
In a new study appearing in the Cell Press journal Structure, researchers from Arizona State University describe their investigations, which reveal the structure of Taspase 1 as never before.
The study unveils, for the first time, the catalytically active 3D structure of Taspase 1, revealing a previously unexplored region that is essential for the functioning of the molecule. The structure was solved using X-ray crystallography and confirmed with electron microscopy.
Petra Fromme, director of the Biodesign Center for Applied Structural Discovery, highlights the great importance of the work: “I am so excited that we were able to solve the first structure of the functional active enzyme, as it will have huge implications for the structure-based development on novel anti-cancer drugs.”
The study results show that reducing this critical helical region of Taspase 1 limits protease activity, while eliminating the helical region deactivates Taspase 1 functioning altogether. Earlier research suggests that disabling Taspase 1 activity to block the progression of cancer could be achieved without harmful side-effects.
“We have reported the importance of a previously unobserved long fragment of the protein in the catalytic activity of Taspase1, which can be used as attractive target to inhibit Taspase1,” according Jose Martin-Garcia, lead scientist on the project and co-correponding author with professor Fromme. “The crystal structure of the active Taspase1 reported in our article will be greatly beneficial to advance the design of Taspase1 inhibitors for anti-cancer therapy.”
Martin-Garcia is currently a researcher with the Department of Crystallography and Structural Biology at the Spanish National Research Council, Madrid.
Fromme and Martin-Garcia are joined by their Biodesign collaborators Nirupa Nagaratnam, Rebecca Jernigan, Brent L. Nannenga and Darren Thifault, along with their multi-institute colleagues.
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Materials provided by Arizona State University. Original written by Richard Harth. Note: Content may be edited for style and length.

A drop of food coloring slowly spreading in a glass of water is driven by a process known as diffusion. While the mathematics of diffusion have been known for many years, how this process works in living organisms is not as well understood.
Now, a study published in Nature Communications provides new insights on the process of diffusion in complex systems. The result of a collaboration between physicists at Penn, the University of Chile, and Heinrich Heine University Düsseldorf, this new theoretical framework has broad implications for active surfaces, such as ones found in biofilms, active coatings, and even mechanisms for pathogen clearance.
Diffusion is described by Fick’s laws: Particles, atoms, or molecules will always move from a region of high to low concentration. Diffusion is one of the most important ways that molecules move within the body. However, for the transport of big objects over large distances, standard diffusion becomes too slow to keep up.
“That’s when you need active components to help transport things around,” says study co-author Arnold Mathijssen. In biology, these actuators include cytoskeletal motors that move cargo vesicles in cells, or cilia that pump liquid out of human lungs. When many actuators accumulate on a surface, they are known as “active carpets.” Together, they can inject energy into a system in order to help make diffusion more efficient.
Mathijssen, whose research group studies the physics of pathogens, first became interested in this topic while studying biofilms with Francisca Guzmán-Lastra, an expert on the physics of active matter, and theoretical physicist Hartmut Löwen. Biofilms are another example of active carpets since they use their flagella to create “flows” that pump liquid and nutrients from their environment. Specifically, the researchers were interested in understanding how biofilms are able to sustain themselves when access to nutrients is limited. “They can increase their food uptake by creating flows, but this also costs energy. So, the question was: How much energy do you put in to get energy out?” says Mathijssen.
But studying active carpets is difficult because they don’t align neatly with Fick’s laws, so the researchers needed to develop a way to understand diffusion in these non-equilibrium systems, or ones that have added energy. “We thought that we could generalize these laws for enhanced diffusion, when you have systems that do not follow Fick’s laws but may still follow a simple formula that is widely applicable to many of these active systems,” Mathijssen says.
After figuring out how to connect the math needed to understand both bacterial dynamics and Fick’s laws, the researchers developed a model similar to the Stokes-Einstein equation, which describes the relationship with temperature and diffusion, and found that microscopic fluctuations could explain the changes they saw in particle diffusion. Using their new model, the researchers also found that the diffusion generated by these small movements is incredibly efficient, allowing bacteria to use just a small amount of energy to gain a large amount of food.
“We’ve now derived a theory that predicts the transport of molecules inside cells or close to active surfaces. My dream would be that these theories would be applied in different biophysical settings,” says Mathijssen. His new research lab at Penn will start working on follow-up experiments to test out these new models. They plan to study active diffusion both in biological and engineered microscopic systems.
Mathijssen, who is also involved on a project related to the spread of COVID-19 in food-processing facilities, says that the cilia in lungs are another important example of active carpets in biology, especially since they serve as the first line of defense against pathogens like COVID-19. He says, “That would be another very important thing to test, whether this theory of active carpets may be linked to the theory of pathogen clearance in the airways.”
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Materials provided by University of Pennsylvania. Original written by Erica K. Brockmeier. Note: Content may be edited for style and length.

Teenagers are more likely to get hooked on marijuana, stimulants and other recreational drugs than college-aged or older adults.Adolescents and teenagers who experiment with marijuana and prescription drugs are more likely to get hooked on them than young people who try these drugs for the first time when they are college-aged or older, according to a new analysis of federal data.The research suggests that young people may be particularly vulnerable to the intoxicating effects of certain drugs, and that early exposure might prime their brains to desire them. The findings have implications for public health policymakers, who in recent years have called for increased screening and preventive measures to reverse a sharp rise in marijuana vaping among teenagers.The new study, published in JAMA Pediatrics and led by a team of scientists at the National Institute on Drug Abuse, sought to gain a better understanding of how adolescent brains respond to a variety of recreational drugs. Previous research suggested that early exposure to marijuana, nicotine and alcohol might lead to faster development of substance use disorders. But the new analysis cast a wider net, looking at the effects of nine different drugs, including opioid painkillers, stimulants, marijuana, alcohol, cigarettes, cocaine, heroin, methamphetamine and tranquilizers.The researchers used data from the government’s National Survey on Drug Use and Health, a closely watched annual study that tracks substance use and mental health issues among Americans. The new research focused on two age groups: adolescents between the ages of 12 and 17, and young adults aged 18 to 25. Alcohol was by far the most commonly used substance in both groups: A quarter of adolescents and 80 percent of young adults said they had used it. About half of young adults said they had tried cannabis or tobacco. But among adolescents, that number was smaller: Roughly 15 percent said they had experimented with cannabis, and 13 percent said they had tried tobacco.Most troubling to the authors of the new study was how many people went on to develop a substance use disorder, indicating that their experimentation had spiraled into an addiction. The researchers found that within a year of first trying marijuana, 11 percent of adolescents had become addicted to it, compared to 6.4 percent of young adults. Even more striking was that within three years of first trying the drug, 20 percent of adolescents became dependent on it, almost double the number of young adults.Adolescents who tried prescription drugs were also more likely to become addicted. About 14 percent of adolescents who took prescription stimulants for recreational use went on to develop a substance use disorder within one year, compared to just 4 percent of young adults. And while 7 percent of young adults who tried opioid painkillers became addicted soon after taking them, that figure rose to 11.2 percent among younger users.For alcohol and tobacco, however, there was not much of a difference between the two age groups: Both older and younger youth had a similar rate of developing a substance use disorder. And for illicit drugs such as cocaine and heroin, the number of adolescents using them was too small for the researchers to draw any meaningful conclusions.One possible explanation for the findings is that young people who have a greater predisposition to developing an addiction may be more likely to seek out illicit drugs at an earlier age. But Dr. Nora Volkow, a senior author of the new study and the director of NIDA, said it is known that cannabis and other drugs can have a potent effect on adolescent brains because they are still developing. Younger brains exhibit greater plasticity, or ability to change, than the relatively static brains of older individuals. As a result, drugs like cannabis are more likely to alter synaptic connections in younger brains, leading to stronger memories of pleasure and reward.“It’s a learning process when you become addicted,” said Dr. Volkow. “It’s a type of memory that gets hard-wired into your brain. That occurs much faster in an adolescent brain.”Studies show that regularly using marijuana can affect cognition in adolescents, leading to impairments in parts of the brain that are involved in learning, reasoning and paying attention. Yet in recent years the booming popularity of e-cigarettes has led to a sharp increase in the number of adolescents who vape nicotine and marijuana, a trend that has alarmed public health officials. Some studies suggest that adolescents may also be more likely to try marijuana as more and more states legalize its recreational use.Dr. Volkow said that as states implement new marijuana regulations, policymakers should work on measures aimed at protecting adolescents. She stressed that pediatricians and dentists should screen for drug use in their young patients by asking them about it. And she cautioned parents not to dismiss marijuana use in teens and adolescents as something that is harmless.“As it relates to marijuana, the drugs that were available when parents today were teenagers are very different from the drugs that are available now,” she said. “The content of THC is much higher, and the higher the THC content, the greater the risk of adverse effects.”

California continued its uneven progress in reopening schools on Monday, as elementary students began to return to classrooms in Long Beach, the state’s fourth-largest district with 70,000 students.Public schools in the state’s top three districts by enrollment — Los Angeles, San Diego and Fresno — have said they will begin to allow grade-school students back onto campus later in April, as new coronavirus cases have fallen sharply across California.Schools in Oakland and San Francisco also are scheduled to reopen next month for elementary and special-needs students. But labor agreements in both cities have allowed substantial numbers of teachers to opt out, leaving some schools without enough teachers to reopen and prompting others to scramble for substitutes.Although many smaller California districts have been open for months, large urban districts on the West Coast generally have lagged behind their counterparts in the rest of the nation. Surging infections in Southern California after the winter holiday were partly to blame for a slow rebound in the Los Angeles school system.Teachers’ unions generally are more powerful in Democratic-led Washington, Oregon and California than in many other states, and teachers have been wary of returning to what they regard as a hazardous workplace, despite federal guidance that elementary schools in particular are safe when health precautions are followed.The Long Beach school district has been able to open earlier than other large California school systems because labor unions there agreed last summer to reopen as soon as health conditions permitted, and because the city was able to start vaccinating teachers earlier than other districts in the state.Unlike most other cities in Los Angeles County, Long Beach has its own public health department, giving the city its own vaccine supplies and the power to set its own vaccine priorities, at a time when the county as a whole was making teachers wait until after other groups, like residents 65 and older, were vaccinated.“A city with its own health department has the ability to be more nimble,” said Jill Baker, the city’s schools superintendent, who called the return to classrooms this week “exciting and momentous.”The school district is among the city’s largest employers, and two-thirds of its students qualify for free or reduced-price lunches, so vaccinating school employees and reopening classrooms was viewed as economically important, Ms. Baker said.About 14,000 students in Long Beach from transitional kindergarten through fifth grade will return this week to school buildings for masked, sanitized and socially distanced instruction. They will be on a hybrid schedule, with students spending about 2½ hours at school each day, five days a week, and completing the school day with remote instruction.In-person classes for older students are scheduled to resume April 19, with grades 6 to 8 getting the option to return on April 20 and grades 9 to 11 on April 26. The last day of school will be in mid-June.

It’s not uncommon for people who experience a concussion to have moderate to severe headaches in the weeks after the injury. A new study has found a combination of two drugs, both common anti-nausea medications, given intravenously in the emergency room may relieve those headaches better than a placebo. The study is published in the March 24, 2021, online issue of Neurology®, the medical journal of the American Academy of Neurology.
Metoclopramide is an anti-nausea medicine sometimes used to treat migraine. Diphenhydramine is a common antihistamine that when used in its injected form can treat motion sickness. Higher doses of metoclopramide given intravenously can cause restlessness, so this study combined diphenhydramine with metoclopramide to prevent those symptoms.
“The headaches you get after a trauma like a fall, an assault or car accident can linger for months or even years and lead to a reduced quality of life, so the results of our study are promising,” said study author Benjamin W. Friedman, M.D., of Albert Einstein College of Medicine, Bronx, N.Y.
The study involved 160 people who experienced a head trauma and then visited an emergency room because of a headache within 10 days. They were randomly assigned to two groups: 81 people were given 20 milligrams (mg) of metoclopramide and 25 mg of diphenhydramine intravenously. The remaining 79 people were given an injection of saline solution as a placebo.
Researchers asked people to rate the intensity of their pain on a scale of zero to 10 one hour after the medication was administered. On this scale, zero means no pain and 10 means the worst pain imaginable.
The study found that the drug combination reduced the average person’s pain level by more than five points one hour later. People in the group given the combination of metoclopramide and diphenhydramine said they improved, on average, by 5.2 points on the pain scale. People in the group given a placebo, on average, said their pain improved by 3.8 points on the pain scale.
In the group given the drug combination, 43% experienced side effects like drowsiness, restlessness or diarrhea. In the group given the placebo, 28% of the people reported those kinds of side effects.
“More research is needed to determine the most effective dose of metoclopramide, and how long to administer it, to see if people can get longer-term relief after they leave the emergency room,” Friedman said. “Also, future work may be able to determine whether early treatment with this medication can target other disruptive symptoms you may get after a head injury, like depression, sleep disorders and anxiety.”
A limitation of the study is that the study participants came from high poverty areas of the country, and may have had less access to care. Because successful headache treatment may be associated with access to care, these results may not apply to the general population.
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Materials provided by American Academy of Neurology. Note: Content may be edited for style and length.

A Japanese research group combined motion analysis that uses smartphone application and machine learning that uses an anomaly detection method, thereby developing a technique to easily screen for carpal tunnel syndrome. Carpal tunnel syndrome is common amongst middle-aged women. The disease causes compressed nerves in the wrist, causing numbness and difficulty with finger movements. While an accurate diagnosis can be reached with nerve conduction study, this is not widely used because it requires expensive devices and specialized skills. Thus, a simple screen tool that does not require any specialized knowledge or techniques is desired.
The research group of Dr. Koji Fujita of Tokyo Medical and Dental University and associate professor Yuta Sugiura of Keio University focused on increasingly poor movements of the thumb with the advancement of the disease, and analyzed its characteristics. They developed a game application for smartphones that is played using the thumbs and prepared a program that acquires the trajectory of the thumb during a game play and estimates the possibility of the disease with machine learning. The application can screen for possible carpal tunnel syndrome using a simple game that can be played in 30 sec — 1 minute. Even without gathering patient data, they were able to effectively construct an estimate mode from the data of 12 asymptomatic participants using the anomaly detection method. When this program was applied to 15 new asymptomatic subjects and 36 patients with carpal tunnel syndrome to verify its accuracy, the result was promising with 93% sensitivity, 69% specificity, and 0.86 Area Under the Curve (AUC)(1). This is equivalent or better than the results of physical examinations by expert orthopedic surgeons.
The developed tool can be used to screen for possible carpal tunnel syndrome at sites where no expert is present, such as at home or at a health center. In the future, the research group aims to develop a system that is able to encourage an examination by an expert when the disease is suspected in order to prevent exacerbation. It would prevent inconvenience and social loss associated with exacerbation of a disease, which is more common among women, and contribute to creating a society where women play an active role.
The research was conducted as part of JST’s Strategic Basic Research Program, Precursory Research for Embryonic Science and Technology (PRESTO).
(1) Area Under the Curve (AUC)
This assessment item is used for each test method, and a higher value indicates a better test. Sensitivity is the ratio of correct positive results for subjects with a disease. Specificity is the ratio of correct negative results for subjects without a disease. AUC is the comprehensive assessment indicator of accuracy that combines sensitivity and specificity and takes a value between 0 and 1.
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Materials provided by Japan Science and Technology Agency. Note: Content may be edited for style and length.