Publisher Health

Neuropathic pain is a debilitating condition estimated to affect as much as 10% of the global population. It results from a damaged or malfunctioning nervous system, stemming from diseases like diabetes, alcoholism, strokes, Parkinson’s and other causes like spinal nerve compression, radiation and chemotherapy treatments.
Management of neuropathic pain has been particularly challenging as currently prescribed drugs, such as anticonvulsants and antidepressants can have severe adverse effects, are not well-tolerated, take a longer time to work only help a subset of patients. Opioids come with the risk of physical dependence and addiction.
Researchers from Boston University Chobanian & Avedisian School of Medicine in collaboration with the Icahn School of Medicine, Columbia University and the New York State Psychiatric Institute used experimental models to explore the cellular actions of tianeptine and provide insight for the development of more effective and safer treatments of neuropathic pain conditions. In a study published today in the journal Neuropsychopharmacology the investigators report that the atypical antidepressant tianeptine potentially provides rapid and lasting pain relief with a low risk of addiction.
“We hope this revives the potential of using tianeptine for the treatment of chronic pain and associated conditions, such as anxiety and depression,” said Venetia Zachariou, PhD, corresponding author of the study and professor and Edward Avedisian Chair of Pharmacology, Physiology & Biophysics at Boston University Chobanian & Avedisian School of Medicine. “By further refining this molecule, we could arrive at a pain treatment that is more effective, fast acting, and has a mild side effect profile.
Researchers used experimental models to investigate the persistent mechanical allodynia that is associated with damaged sciatic nerve, comparing the therapeutic profiles of tianeptine to that of the antidepressant desipramine.
To better understand the mechanisms underlying the drug’s effects, the investigators used RNA sequencing, to monitor gene expression changes in the nucleus accumbens, a brain region involved in motivation, addiction, and pain perception to identify pain-related genes that tianeptine treatment counteracts.
The results showed that tianeptine had profound pain-relieving properties that lasted well after the drug was no longer present, which suggested it was the drug affected the expression of genes that were critical for the maintenance of pain symptoms. The researchers also found that tianeptine started working more quickly than other antidepressants.
Tianeptine is prescribed in some European, Asian and Latin American countries in low doses to treat depression, and in higher doses for asthma, anxiety and other conditions. Since tianeptine actions require endogenous opioid receptors; U.S. regulators have not approved it for use here.
“Several studies have shown that the abuse potential of tianeptine is substantially lower than other currently abused opioids such as oxycodone. Furthermore, also based on prior studies, tianeptine does not appear to cause tolerance, so the dose does not need to be increased drastically over time as we see with opioids, which contributes to physical dependance and addiction,” said Zachariou and Alex Serafini, PhD, a postdoc in BU’s pharmacology, physiology & biophysics department and first author of the paper. “The data from this study contributes to a much larger set of data supporting the use of this drug for conditions such as chronic pain.”

Taking a significant leap in the field of vaccine development, Western researchers have discovered a potential ‘super molecule’ that can bolster the effectiveness of several vaccines against viral diseases, including influenza, COVID-19 and smallpox.
A team led by Western professor Mansour Haeryfar found that a vitamin B2-derived molecule called 5-OP-RU, which is produced by bacteria, can enhance the efficacy of several vaccines for viral diseases.
The study revealed the molecule binds to a protein called MR1 before stimulating a population of T lymphocytes called mucosa-associated invariant T (MAIT) cells — essentially, one of the “first responders” that come rushing to fight off infection when a virus invades the body.
The findings, recently published in PLOS Pathogens, could have significant implications for strengthening the global response to current and future viral threats.
“We need better vaccines to combat viruses of pandemic potential, which are among the most vicious existential threats to human populations,” said Haeryfar, professor of immunology at Western’s Schulich School of Medicine & Dentistry.
“Our strategy of targeting the MR1-MAIT cell axis using 5-OP-RU shows promise in generating strong antiviral immune responses in the body. This strategy could help develop more effective viral vaccines.”
For the study, the team of researchers used a combination of clinically relevant mouse models, human cell cultures and multiple vaccine platforms against various influenza, SARS-CoV-2 and smallpox. They found that 5-OP-RU worked in tandem with antiviral vaccines to expand MAIT cells and reprogram them to become more powerful antiviral entities.

Women with a history of endometriosis had higher concentrations of cadmium in their urine compared to those without that diagnosis, according to a Michigan State University study that suggests the toxic metal could be linked to the development of endometriosis.
Affecting one in 10 reproductive-age women, endometriosis is a gynecologic condition in which tissue that looks like the lining of the uterus, or womb, appears outside the uterus. Those with endometriosis can experience chronic, painful and debilitating symptoms, which can interfere with all aspects of life, including daily activity, work productivity, school performance and personal relationships.
“Despite the adverse impact of endometriosis on quality of life, it remains an understudied condition,” said Kristen Upson, assistant professor in the Department of Epidemiology and Biostatistics at the MSU College of Human Medicine and senior author of the study.
“By looking at environmental risk factors such as metal cadmium, we are moving the needle closer to understanding risk factors for this condition,” added the study’s first author, Mandy Hall, a data analyst in the MSU Department of Epidemiology and Biostatistics.
Cadmium is a toxic metal and a “metalloestrogen,” meaning it can act like the hormone estrogen. In the U.S., people are commonly exposed to cadmium by breathing in cigarette smoke and eating contaminated food like spinach and lettuce.
While this is not the first study exploring a potential link between cadmium and endometriosis, the researchers said it’s the largest study to look at cadmium measured in urine, which reflects long-term exposure between 10 and 30 years.
For their study, researchers used data from the National Health and Nutrition Examination Survey, or NHANES, a national study representative of the U.S. population between 1999 and 2006. Out of the survey’s more than 41,000 participants, the researchers limited their study population to those 20 to 54 years of age with information on endometriosis diagnosis.

Among nearly 10 million US infants born between 2016 and 2018, breastfed babies were 33% less likely to die during the post-perinatal period (day 7-364) than infants who were not breastfed, reports a new study in the American Journal of Preventive Medicine, published by Elsevier. The findings build on previous US research with smaller datasets, which documented the association between the initiation of breastfeeding and the reduction of post-perinatal infant mortality by a range of 19% to 26%.
Lead investigator Julie L. Ware, MD, MPH, Division of General and Community Pediatrics, Department of Pediatrics, Cincinnati Children’s Center for Breastfeeding Medicine, said, “Based on these data, there is clear evidence that breastfeeding confers a protective benefit during the first year of life and is strongly associated with reduced post-perinatal infant mortality across the USA.”
Dr. Ware noted that the findings suggest there is an opportunity for breastfeeding promotion, protection, and support to be included as a key component in comprehensive infant mortality reduction initiatives in regions and states across the US.
With help from the Centers for Disease Control and Prevention (CDC) National Center for Health Statistics, birth certificate data on US infants born from 2016 to 2018 were linked with infant deaths occurring up to one year after birth. An analysis was conducted to demonstrate whether the initiation of breastfeeding, as recorded on the birth certificate (a practice adopted by all states in 2016), was associated with post-perinatal infant death, taking into account factors such maternal age, education, race and ethnicity, and geographical location.
Breastfeeding is recognized by the World Health Organization, American Academy of Pediatrics, and other authorities as the preferred normative nutrition for infants, both recommending that families breastfeed their infants exclusively for 6 months, continuing with the addition of complementary foods for at least the first 2 years of life. These organizations consider breastfeeding a public health imperative with many short- and long-term improved health outcomes for both mother and child, including significant reductions in all-cause infant mortality and specific protection against sudden infant death syndrome and necrotizing enterocolitis in preterm infants. Despite these recommendations, the rates for breastfeeding initiation, exclusivity, and continuation in the US do not meet breastfeeding goals, especially in certain racial and ethnic populations, and in some geographic regions.
Co-investigator Ardythe Morrow, PhD, University of Cincinnati College of Medicine stated that, “Though breastfeeding is widely recommended, nevertheless, some may still consider it to be of minor importance. We hope that our findings will change the narrative. Human milk is replete with protective molecules, and breastfeeding offers significant protection.”
Addressing breastfeeding disparities may improve the health of mothers and their babies and help reduce adverse outcomes. Although most states advocate breastfeeding promotion, protection, and support activities, analysis of the association between breastfeeding and infant mortality had not previously been conducted at the state and regional levels. To this end, the investigators conducted a regional and state-by-state analysis.
Co-investigator Aimin Chen, PhD, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, explained, “We found that the effect was evident across the US, but with regional variations, ranging from 44% in the Northeast and Mid-Atlantic, where breastfeeding initiation is the highest, and 21% in the Southeast, where breastfeeding initiation is the lowest. Although regional and state variation in the magnitude of the association between breastfeeding and infant mortality exists, there was a remarkable consistency of reduced risk. Together with existing literature, our data suggest that breastfeeding promotion and support may be an effective strategy to help reduce infant mortality in the US.”

The discovery of insulin has saved the lives of millions of people with diabetes worldwide, but little is known about the first step of insulin synthesis.
Researchers at the University of Michigan have uncovered part of this mystery. Examining messenger RNAs involved in the production of insulin in fruit flies, they found that a chemical tag on the mRNA is crucial to translating the insulin mRNA into the protein insulin. The alteration of this chemical tag can affect how much insulin is produced.
The study, conducted by researchers Daniel Wilinski and Monica Dus, is published in the journal Nature Structural and Molecular Biology.
An organism carries DNA — its genes — in each cell of its bodies. Genes are blocks of information that get transcribed into proteins via another molecule called messenger RNAs. These mRNAs are photocopies of DNA — leaving the original DNA untouched — that ferry this protein information into the cytoplasm of cells, where protein is synthesized. The mRNAs are decorated with small molecules called “tags.” These tags can modify how RNAs function and how proteins are produced.
“I like to think of RNA as a Christmas tree,” said Wilinski, a postdoctoral researcher in Dus’ lab in the U-M Department of Molecular, Cellular and Developmental Biology. “Christmas trees are beautiful in the wilderness, but when you bring them inside and put ornaments on them, that decoration is what makes you feel like the tree is part of the season. Same thing with RNA. These decorations on RNA really enhance the way RNA is regulated.”
Studying insulin production in humans or mammals is difficult. In humans, the pancreas is situated behind the liver. It doesn’t regenerate well, and it can’t be sampled in live subjects. But in flies, their insulin cells are actually in their brains, function like neurons, and are physically accessible to researchers. In fruit flies, the researchers looked at a tag called RNA N-6 adenosine methylation, or m6A.
To study the m6A tag, the researchers first identified the RNAs that have the tag. Then they labeled insulin cells with a fluorescent molecule, and used confocal microscopy to visualize how much insulin is produced by the insulin cell. They did this under two conditions: first, they knocked out the m6A enzyme, responsible for decorating the mRNA with m6A tags, in insulin cells. Second, they removed the m6A tags by using CRISPR, a technology used to edit DNA, to mutate the modified As.

Workers making artificial-stone slabs for the most popular type of countertops sold in the United States are developing a potentially deadly, irreversible lung disease from tiny particles of toxic dust, researchers from UC San Francisco and UCLA found in the largest U.S. study of this emerging health crisis.
When the synthetic quartz is cut, ground and polished, lung-damaging dust is released into the air, leading to a disease called silicosis. The disease has plagued miners and cutters of natural stone for centuries, but the engineered stone is far more dangerous due to its high concentration of silica, a natural product in sandstone, and the harmful polymer resins and dyes that are added to the engineered product.
This growing occupational hazard has been sickening and claiming the lives of workers, predominantly young Latino men, at an alarming rate since the first U.S. silicosis case due to engineered stone was reported in 2015, according to the study published in the July 24, 2023, edition of JAMA Internal Medicine.
“Increasing case counts of silicosis among stone fabricators over the last 10 years and accelerated progression of disease transforms the paradigm of an all-but-previously-forgotten disease in the U.S.,” said Jane Fazio, MD, a pulmonary specialist at Olive View-UCLA Medical Center and co-author of the study. “Our study demonstrates severe morbidity and mortality among a particularly vulnerable group of young underinsured and likely undocumented Latino immigrant workers.”
The human cost of engineered quartz
The risk of silicosis from artificial stone was first identified in Israel in 2012. Since the first U.S. case of silicosis linked to engineered stone was identified in Texas in 2015, California has become an epicenter of the disease.
Researchers from UCSF and UCLA collaborated with the UCSF California Labor Laboratory and the California Department of Public Health to identify 52 California engineered-stone workers diagnosed with silicosis, 51 of whom were Latino immigrants. Most were diagnosed between 2019 and 2022. Twenty of the patients had advanced disease at diagnosis, and have 10 died. Their median age was 45 years old, with an average work history of 15 years.

Although infections can present with many different symptoms, one common symptom is the loss of fat and muscle, a process called wasting. Salk scientists wanted to know whether wasting was beneficial in fighting infections.
Researchers in Professor Janelle Ayres’ lab discovered the wasting response to T. brucei infection in mice occurs in two phases, each regulated by different immune cells. While fat loss did not benefit the fight against infection, muscle loss did — a surprising clue that some wasting may help manage illness.
The findings, published in Cell Reports on July 24, 2023, can inform the development of more effective therapeutics that spare people from wasting and increase our understanding of how wasting influences survival and morbidity across infections, cancers, chronic illnesses, and more.
“We oftenmake assumptions that conditions like wasting are bad, since they often coincide with higher mortality rates,” says senior author Ayres, Salk Institute Legacy Chair and head of the Molecular and Systems Physiology Laboratory. “But if instead we ask, what is the purpose of wasting? We can find surprising and insightful answers that can help us understand the human response to infection and how we can optimize that response.”
Defending the body from an invader requires a lot of energy. Prior studies suggested this immune-related energy consumption had the unfortunate consequence of wasting. But Ayres and team were curious to know whether wasting could be beneficial and not just a side effect.
Specialized immune cells called T cells are slow to respond to infections, but when they do respond, they adapt to fight the particular infection. Ayres was interested to know whether it was these T cells causing wasting. If T cells are responsible for the condition, that would indicate wasting is not simply an unproductive side effect of energy-hungry immune cells.
The cells of interest are called CD4+ and CD8+ T cells. CD4+ T cells lead the fight against infection and can promote the activity of CD8+ T cells, which can kill invaders and cancerous cells. The two T cell types often work together, so the researchers hypothesized their role in wasting may be a cooperative effort, too.

A busy, crowded, confusing emergency room is not an ideal place for a person living with dementia.
But 1.4 million times a year, people with Alzheimer’s disease and other forms of dementia end up in emergency care, a new study shows.
Together, they make up nearly 7% of all emergency visits for any reason by people over age 65, according to a University of Michigan team’s findings published in JAMA Neurology.
And compared with their peers who don’t have dementia, these patients have twice the rate of seeking emergency care after an accident or a behavioral or mental health crisis, the researchers show.
With about 6 million Americans currently estimated to have dementia, the study suggests there’s a lot of opportunity to prevent future emergency visits by better supporting dementia caregivers, thereby, the researchers say.
Lead author Lauren B. Gerlach, D.O., M.Sc., says the findings could help inform efforts to support family caregivers and nursing facility staff in reducing patients’ risks of injury, and preventing the agitation, aggression and distressing behaviors that people with dementia can experience.
“While dementia is thought of as a cognitive or memory disorder, it is the behavioral aspects of the disease such as anxiety, agitation and sleep disturbances that can cause the most stress for caregivers and patients alike,” said Gerlach, a geriatric psychiatrist at Michigan Medicine, U-M’s academic medical center. “Emergency departments are often not the right place to manage these behaviors,” she added. “We really need to do better to support caregivers so there are options other than seeking emergency care.”
Once a person with dementia is in the emergency department, it can be a very disorienting experience, Gerlach explains. “This is especially true in the context of a busy ED where visits can last many hours and patients may have difficulty understanding what is occurring or communicating their needs,” she said. “Even routine blood draws from unfamiliar staff can be a very scary experience for a patient with advanced dementia.”

A gene called Myc (pronounced “mick”) that is among the most important drivers of cancer in both mice and humans also plays a newly discovered crucial role in aging, according to a new Cell Reports study by researchers at UPMC Children’s Hospital of Pittsburgh and the University of Pittsburgh School of Medicine.
The research, led by Edward V. Prochownik, M.D., Ph.D., the Paul C. Gaffney Professor of Pediatrics in the Division of Hematology/Oncology at UPMC Children’s and professor in the Department of Microbiology and Molecular Genetics, has implications for newer forms of cancer therapy.
Myc has traditionally been difficult to study because when it’s eliminated in mouse embryos, they die before birth, indicating that the gene plays fundamental roles in normal growth and development. According to Prochownik, this made it virtually impossible to understand the role of Myc beyond this embryonic stage. To overcome this major hurdle, Prochownik and his team waited until the mice were about 1 month old to inactivate the gene.
“Given how important Myc is for both normal and cancer tissues, a critical question we had was whether these mice would die just like the embryos did,” said Prochownik. “We waited nervously during the first several days after eliminating the gene in the first group of mice, and we were relieved to find that they survived. This allowed us to study the mice for much longer, which is what we had always hoped to do.”
Within weeks of eliminating Myc, the researchers noted that the mice started to age rapidly: They had greyer coats, lost some of their fur and were weaker, less coordinated and less active than normal mice of the same chronological age. They also developed many metabolic abnormalities often associated with aging.
However, despite aging faster, the mice lived up to 20% longer.
“At first, we were unable to explain the puzzling finding that the rapidly aging mice lived longer,” said Prochownik. “The answer became apparent only at the end of the study when we compiled autopsy results on mice that died naturally. The rate of cancer in the Myc knockout mice was more than three times lower than in normal mice.”
Prochownik speculates that mice lacking the Myc gene, which is so important for the development of cancer, were unable to develop tumors. This theory is supported by the finding that of the few tumors that did occur in the knockout mice, most re-expressed Myc, indicating that tumors tended to arise from a small population of cells that had managed to escape inactivation of Myc from the very beginning.

While the incidence of influenza-associated neuropsychiatric events in children in the United States is unknown, the controversy over the use of a common antiviral medication typically administered to treat flu in children has sparked concern among parents and medical professionals alike.
The dilemma about whether the treatment causes neuropsychiatric events or if the infection itself is the culprit, led a group of pediatric researchers at Monroe Carell Jr. Children’s Hospital at Vanderbilt to study the question.
“Population-Based Incidence of Influenza-Associated Serious Neuropsychiatric Events in Children” published in the Journal of the American Medical Association (JAMA) Pediatrics examines how often children diagnosed with flu experience serious neuropsychiatric side effects.
“We are among the first to quantify these serious events in the pediatric population in the United States,” said principal investigator James Antoon, MD, PhD, MPH, assistant professor of Pediatrics and Hospital Medicine at Monroe Carell. “We knew some of the neurological events occurred, but we did not know how often and in whom.
“Our study quantified the number of pediatric neuropsychiatric events, described which children are more likely to experience the events and showed that these events occur in both those children treated and not treated with an antiviral. Ongoing studies will help us assess if use of influenza antivirals is associated with the risk of neuropsychiatric events in children,” Antoon said.
“This study highlights the importance of understanding the frequency and context in which neuropsychiatric events occur … especially among young children and children with underlying conditions who are also at high risk for influenza complications,” said senior author Carlos Grijalva, MD, MPH, professor of Health Policy and Biomedical Informatics at Vanderbilt University Medical Center.
According to the study, Oseltamivir, known as Tamiflu, has a black box warning about neuropsychiatric side effects. Previous studies have been mixed on whether using Tamiflu causes these events.