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Kidney stones affect nearly 10% of the global population. For more than three decades, thiazide diuretics, a common medication used for high blood pressure, have been the standard of care for kidney stone prevention because they reduce the excretion of urinary calcium.
However, recent clinical trials have raised doubts about their efficacy in preventing kidney stones. The NOSTONE trial, published in The New England Journal of Medicine in March 2023, failed to find a protective effect of thiazide diuretics on kidney stone disease.
A new Vanderbilt University Medical Center genetic association study of more than 1 million adults challenges those findings. The study, published in JAMA Network Open,used genetic markers to mimic the effect of thiazide diuretics to estimate the long-term medication effect.
“We found that these genetic proxies of thiazide diuretics were associated with a 15% lower risk of kidney stones,” said Jefferson Triozzi, MD, the lead author and nephrology fellow pursuing a Master of Science in Clinical Investigation. “Furthermore, we examined serum laboratory values relevant to the treatment of kidney stones and found that the genetic proxies of thiazide diuretics were associated with higher serum calcium levels, supporting the notion that thiazides affect kidney stone risk by modulating calcium excretion in the urine.”
Most of the adults in the study were participants in the VA Million Veteran Program (MVP), a national research program that examines the effect of genetics, lifestyle and other factors on veterans’ health and wellness.
“The VA Million Veteran Program is the largest and most diverse biobank in the world, now with 1 million participants as of Nov. 11,” said Adriana Hung, MD, MPH, associate professor of Medicine, Division of Nephrology, and senior investigator for this manuscript. “Unique resources like the MVP, with extensive data on clinical condition combined with genomic data, provide a valuable resource for genetically informed drug discovery and drug repurposing. Thiazide diuretics are recommended by international guidelines for the prevention of calcium kidney stones with long-term safety data.”
The all-VUMC team of researchers plans to investigate the underlying mechanisms by which thiazide diuretics lower the risk of kidney stones next.
“Our study highlights the importance of considering genetic proxies to estimate the long-term effects of medications and offers new evidence to support the use of thiazide diuretics for kidney stone prevention,” Triozzi said. “We believe genetic data can help us understand drug mechanisms and perhaps lead to new drug discovery for kidney stone disease.”

Transitioning away from per- and polyfluoroalkyl substances (PFAS), which offer water- and oil-repelling properties on the outer shells of firefighter turnout gear, could bring potential performance tradeoffs, according to a new study from North Carolina State University.
The study showed that turnout gear without PFAS outer shell coatings were not oil-repellent, posing a potential flammability hazard to firefighters if exposed to oil and flame, said Bryan Ormond, assistant professor of textile engineering, chemistry and science at NC State and corresponding author of a paper describing the research.
“All oil repellents can also repel water, but all water repellents don’t necessarily repel oil,” Ormond said. “Diesel fuel is really difficult to repel, as is hydraulic fluid; in our testing, PFAS-treated materials repel both. In our tests, turnout gear without PFAS repelled water but not oil or hydraulic fluid.
“Further, oils seem to spread out even more on the PFAS-free gear, potentially increasing the hazard.”
PFAS chemicals — known as forever chemicals because of their environmental persistence — are used in food packaging, cookware and cosmetics, among other uses, but have recently been implicated in higher risks of cancer, higher cholesterol levels and compromised immune systems in humans. In response, firefighters have sought alternative chemical compounds — like the hydrocarbon wax coating used in the study — on turnout gear to repel water and oils.
Besides testing the oil- and water-repelling properties of PFAS-treated and PFAS-free outer garments, the NC State researchers also compared how the outer shells aged in job-related exposures like weathering, high heat and repeated laundering, and whether the garments remained durable and withstood tears and rips.
The study showed that PFAS-treated and PFAS-free outer shells performed similarly after exposure to UV rays and various levels of heat and moisture, as well as passes through heating equipment — similar to a pizza oven — and through washing machines.

“Laundering the gear is actually very damaging to turnout gear because of the washing machine’s agitation and cleaning agents used,” Ormond said.
“We also performed chemical analyses to see what’s happening during the weathering process,” said Nur Mazumder, an NC State doctoral student in fiber and polymer science and lead author of the paper. “Are we losing the PFAS chemistries, the PFAS-free chemistries or both when we age the garments? It turns out that we lost significant amounts of both of these finishes after the aging tests.”
Both types of garments performed similarly when tested for strength against tearing the outer shell fabric. The researchers say the PFAS and PFAS-free coatings didn’t seem to affect this attribute.
Ormond said that future work will explore how much oil repellency is needed by firefighters out in the field.
“Even with PFAS treatment, you see a difference between a splash of fluid and soaked-in fluid,” Ormond said. “For all of its benefits, PFAS-treated gear, when soaked, is dangerous to firefighters. So we need to really ask ‘What do firefighters need?’ If you’re not experiencing this need for oil repellency, there’s no worry about switching to non-PFAS gear. But firefighters need to know the non-PFAS gear will absorb oil, regardless of what those oils are.”
Andrew Hall, another NC State doctoral student in fiber and polymer science and co-author on the paper, is also testing dermal absorption, or taking the aged outer shell materials and placing them on a skin surrogate for a day or two. Are outer shell chemicals absorbed in the skin surrogate after these admittedly extreme exposure durations?
“Firefighting as a job is classified as a carcinogen and it shouldn’t be,” Ormond said. “How do we make better gear for them? How do we come up with better finishes and strategies for them?
“These aren’t just fabrics,” Ormond said. “They are highly engineered pieces of material that aren’t easily replaced.”
The paper appears in the Journal of Industrial Textiles. Funding for the research came from the Federal Emergency Management Agency’s Assistance to Firefighters Grants Program.

Published5 days agoShareclose panelShare pageCopy linkAbout sharingThis video can not be playedTo play this video you need to enable JavaScript in your browser.By Kate Whannel & Sam FrancisPolitical reporterEntering lockdown three weeks earlier would have cut deaths in the first Covid wave by 90%, former health secretary Matt Hancock has said.Mr Hancock told the Covid inquiry that with the benefit of hindsight the UK should have locked down much sooner.He also said a “toxic culture” existed in government driven by Dominic Cummings, the PM’s chief advisor.But he denied accusations he lied to colleagues during the pandemic.Mr Cummings – who left No 10 in December 2020 after falling out with then PM Boris Johnson – has been particularly scathing of Mr Hancock.Offered a chance to respond, Mr Hancock called Mr Cummings a “malign actor” who subjected Health Department staff to abuse as they grappled with the emergence of Covid.He argued it was having to do the work of other departments, for example on school closures, and that its “hard work” was hindered by “a toxic culture that we had to work with”.He said Mr Cummings sought to grab power from Mr Johnson while shutting out ministers from key meetings.There was an “unhelpful” assumption that “when anything was difficult or a challenge… there was somehow fault and blame”, Mr Hancock said.The West Suffolk MP was health secretary from 2018 until June 2021, when he was forced to resign after breaching Covid guidance.He was suspended as a Conservative MP, after appearing on ITV’s I’m a Celebrity Get Me Out of Here in 2022 and later said he would not stand for re-election.More on Covid and the Covid InquiryLIVE: Follow the latest updates from the Covid inquiryWhat is the UK Covid inquiry and how long will it take?How inquiry is exposing deep flaws in Covid decision-makingThe private WhatsApp messages from inside Downing StreetWhat to do if you have Covid: Can you go to work or school?During his testimony Mr Hancock said “many, many lives” could have been saved if the UK government had initiated the first coronavirus lockdown around 2 March 2020, rather than 23 March.However, he stressed that there was still “enormous uncertainty” and only 12 cases had been identified in the country by this point.He told the inquiry he was speaking with “hindsight” and robustly defended his role in the pandemic and that of the department he led.”From the middle of January, we were trying to effectively raise the alarm,” he said, adding: “We were trying to wake up Whitehall to the scale of the problem.”Not ‘adequate’Pushed on when he advised Mr Johnson that immediate action would be needed to contain the virus, Mr Hancock said he raised the alarm bell on 13 March.However, the inquiry’s lawyer, Hugo Keith KC, questioned the statement, noting that this was not mentioned in the entry for 13 March in Mr Hancock’s book, Pandemic Diaries. Mr Hancock replied that the evidence only came to light after his diary was published and cited an email he sent the prime minister calling for a “suppression strategy”. Mr Keith argued that this did not amount to calling for an immediate lockdown.Asked about the existence of pre-prepared plans for a pandemic, Mr Hancock said they existed but repeated his previous assertion that they were not “adequate”.Mr Hancock will continue his evidence on Friday. Mr Johnson will give evidence to the inquiry on 6 and 7 December. Prime Minister Rishi Sunak is also expected to give evidence before the end of the year.Image source, EPAThe inquiry has been bruising for the politician, with past witnesses accusing Mr Hancock of “nuclear levels” of overconfidence and a lack of honesty.Helen MacNamara, a senior civil servant during the pandemic, said he would say things that would turn out not to be the case.Sir Patrick Vallance, the former chief scientific adviser, said Mr Hancock had “a habit of saying things which he didn’t have a basis for”. Mr Hancock said there was no “evidence whatsoever” that he lied during the pandemic. In the session, the inquiry was shown extracts from Sir Patrick’s diary which described a “massive internal mess” inside the health department and reported that then-civil service head Sir Mark Sedwill complained of the department’s “clear lack of grip”.Government responseMr Hancock has been criticised for saying in the early days of the pandemic that a “protective ring” had been thrown around care homes.He said he used that phrase to refer to actions including giving the sector £3bn and providing protective equipment. However, he appeared to agree with suggestions that the protections did not amount to “an unbroken circle”.He also told the inquiry that he did not know about the “Eat Out to Help Out scheme” – whereby the government subsidised people to go to restaurants in the summer of 2020 – until the day it was announced.He acknowledged he had concerns about how it impacted infection rates, however he said he did not express those publicly because he abided by “collective responsibility”. ‘Greatest regret’Mr Hancock was also questioned about apparently contradictory evidence on when the government knew people without symptoms could transmit the virus. Referring to a report by the US’s Centre for Disease Control, he said there was not clear evidence until the beginning of April and up to then he had been advised not to base policy on the assumption that transmission could be asymptomatic. Mr Hancock said it was his “single greatest regret with hindsight” that he didn’t overrule the advice.”I was in the pro-let’s worry about asymptomatic transmission camp. The frustration was that, understandably from their point of view, and here I’m putting myself in their shoes, the Public Health England scientists said we have not got concrete evidence.”The inquiry was shown messages between Chief Medical Officer Sir Chris Whitty and Sir Patrick in which they suggest the government had known about asymptomatic transmission. Posting on X as the inquiry was going on, Mr Cummings said Mr Hancock was “talking rubbish”.More on this storyUK’s pandemic strategy was wrong, says HancockPublished27 JuneRaab denies Cummings made key pandemic decisionsPublished6 days agoHow inquiry is exposing deep flaws in Covid decision-makingPublished26 November

Researchers, led by University of Melbourne’s Professor Laura Mackay, a Laboratory Head and Immunology Theme Leader at the Peter Doherty Institute of Infection and Immunity (Doherty Institute), discovered distinct mechanisms controlling different types of immune cells, and found that, by precisely targeting these mechanisms, they could selectively eliminate ‘problematic cells’ and reshape the skin’s immune landscape.
Our skin is packed with specialised immune cells that protect against infections and cancer and promote healing. These cells, called tissue-resident T cells or TRM cells, stay in place to fight infections and cancerous cells in the skin. However, when not controlled properly, some of these skin TRM cells can contribute to autoimmune diseases, such as psoriasis and vitiligo.
University of Melbourne’s Dr Simone Park, an Honorary Research Fellow and former Postdoctoral Fellow in the Mackay Lab at the Doherty Institute, and lead first author of the study, said that this research is the first to describe the unique elements that control various types of skin TRM cells in animal models, offering precise targets for potential treatment strategies.
“Specialised immune cells in our skin are diverse: many are critical to prevent infection and cancer, but others play a big role in mediating autoimmunity,” said Dr Park.
“We discovered key differences in how distinct types of skin T cells are regulated, allowing us to precisely edit the skin’s immune landscape in a targeted way.”
University of Melbourne’s Dr Susan Christo, Senior Research Officer in the Mackay Lab at the Doherty Institute and co-first author of the study, explained how these discoveries could advance efforts to treat skin disease.
“Most autoimmune therapies treat the symptoms of the disease rather than addressing the cause. Conventional treatments for skin disorders often impact all immune cells indiscriminately, meaning that we could also be wiping out our protective T cells,” said Dr Christo.

“Until now, we didn’t know how to pick apart ‘bad’ T cells in the skin from the ‘good’ protective ones. Through this research, we discovered new molecules that allow us to selectively remove disease-causing T cells in the skin.”
In this groundbreaking study published in Science, the research team harnessed this new knowledge to eliminate ‘problematic’ cells that can drive autoimmune disorders, while preserving the ‘good’ ones that are essential to maintain protective immunity.
University of Melbourne’s Professor Laura Mackay, senior author of the study, explained that these findings could pave the way for more precise and long-lasting therapies for skin disease.
“Skin conditions like psoriasis and vitiligo are difficult to treat long-term. The T cells driving disease are hard to remove, so patients often need life-long treatment. Our approach has the potential to revolutionise the way we treat these skin disorders, significantly improving outcomes for people dealing with challenging skin conditions,” said Professor Mackay.
With the study demonstrating successful removal of specific skin T cells in animal models, further research is necessary to validate the efficacy of these strategies in human subjects. Dr Park hopes the study will inspire the development of new treatments for skin disease.
“These discoveries bring us one step closer to developing new drugs that durably prevent autoimmune skin disorders without compromising immune protection,” said Dr Park.

Simulated high altitude could help older patients at risk of health complications related to surgery, a new study has found.
A randomised trial of eight volunteers spent a week exposed to reduced oxygen levels that simulated high altitude in a residential hypoxia facility, to see if breathing less oxygen could benefit their physical health.
The research is published in Anaesthesia by researchers from King’s College London, Royal Melbourne Hospital, Oxford University Hospitals NHS Foundation Trust, Beth Israel Deaconess Medical Center and the University of Limerick.
Many patients waiting to have major surgery have low levels of fitness, high BMI, sedentary lifestyles or anemia, which are associated with higher rates of complications and deaths after surgery. Anaesthetists are urgently trying to develop more effective means of improving fitness before operations, known as prehabilitation, to reduce this possibility.
Altitude training is known to improve fitness and lead to higher blood levels (haemoglobin, which carries oxygen in the body) in athletes through exposure to reduced oxygen levels (hypoxia), which are similar to the conditions passengers experience during an airline flight. In athletes, a low oxygen environment stimulates an increase in haemoglobin to carry more oxygen throughout the body, enabling them to perform better in low-altitude environments.
Researchers questioned whether exposure to simulated high altitude could benefit older people who face a risk of complications ahead of surgery, introducing the concept of ‘altitude prehabilitation’. To test this, they recruited eight sedentary volunteers with an average age of 64 to spend two weeks living in the National Altitude Training Centre in Ireland, a ‘hypoxic house’ in which oxygen levels in the air are tightly controlled.
During one week, the house contained normal air, while during the other week the oxygen levels were mildly reduced (similar to conditions during an airline flight, equivalent to approximately 2438 m or 8000 ft). Volunteers underwent cardiopulmonary exercise tests before and after each week-long exposure.

The researchers found that simulated high altitude stimulated a large increase in haemoglobin in participants but led to no major changes in their aerobic fitness. This increase in haemoglobin could be clinically beneficial ahead of surgery.
In practice, small scale hypoxic canopies could be provided to patients to use while sleeping for the weeks leading up to their surgery. The use of hypoxic technology is also already widespread, as hypoxic rooms or tents are available at high-end gyms and in professional sports clubs, and similar hypoxic air systems are used to prevent fires on an industrial scale, such as in warehouses and library archives. In healthcare settings, hospitals could create small or large hypoxic spaces for patients ahead of surgery, as the technology is available.
Lead author Professor Thomas Smith, a Consultant Anaesthetist and Head of Aerospace Medicine Research at King’s College London, said: “We know that athletes can use hypoxic canopies over their bed to simulate altitude exposure and that altitude can induce performance benefits after two to three weeks even in people who are extremely fit. We were interested in whether this approach could also benefit older patients ahead of major surgery, who due to sedentary lifestyles and low levels of fitness, are more at risk of negative postoperative outcomes.
“Whilst this study suggests that simulated altitude exposure may have potential advantages for older and sedentary patients, further studies are needed to explore this for home-based altitude prehabilitation.”

Indiana University researchers are collaborating on a novel approach to use neuroimaging and network modeling tools — previously developed to analyze brains of patients in the clinic — to investigate Alzheimer’s disease progression in preclinical animal models.
The research team, led by Evgeny Chumin, PhD, a postdoctoral research fellow in the College of Arts and Sciences’ Department of Psychological and Brain Sciences at IU Bloomington, and Paul Territo, PhD, professor of medicine at the IU School of Medicine, published their findings in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
More than 6.5 million Americans ages 65 and older are living with Alzheimer’s disease, and that number could grow to nearly 14 million by 2060, according to the Alzheimer’s Association. While amyloid plaques and tau tangles are the two major hallmarks of Alzheimer’s disease, research studies also indicate that Alzheimer’s disease alters glucose metabolism in the brain.
This study looked at metabolic network changes in the brains of Alzheimer’s disease animal models developed by the Model Organism Development and Evaluation for Late-Onset Alzheimer’s Disease (MODEL-AD), a consortium of experts at the IU School of Medicine, Jackson Laboratory, University of Pittsburgh and Sage Bionetworks. The tools developed through this research collaboration, Territo said, provide a translational approach to assess disease progression of Alzheimer’s disease in animal models and bolster the consortium’s rigorous animal model development and preclinical drug testing pipelines developed to study and treat the disease.
“We now for the first time have created tools to assess mouse models carrying human genes, which are built upon the well-established Brain Connectivity Toolbox used in human studies,” Territo said. “We are applying these tools to better understand Alzheimer’s disease progression and therapeutic response and are embedding them as a resource in MODEL-AD.”
Territo, a primary member of IU School of Medicine’s Stark Neurosciences Research Institute and co-principal investigator of the MODEL-AD consortium, said two past studies inspired his research into analyzing how different areas of the brain interact during disease progression.
Olaf Sporns, PhD, a Distinguished Professor in the Department of Psychological and Brain Sciences at IU Bloomington, has previously published papers about network neuroscience, an approach for monitoring disease progression using graph theory and medical imaging — MRI and PET — to map, record, analyze and model the elements and interactions of neurobiological systems in humans. This allows scientists to see changes that occur in the brain’s subnetworks by elevating how neuroimaging like MRI and PET can be analyzed. Chumin is a postdoctoral researcher in the Sporns laboratory.

Metabolic covariance networks of Alzheimer’s disease animal models showed a lower community structure agreement compared to normal models. Agreement quantifies the propensity of regions in the metabolic network to cluster together, with lower values indicative of disruptions in inter-regional relationships of metabolic activity.
The other research is from Mattia Veronese, PhD, a scientist from King’s College in London and associate professor at the University of Padua in Italy, who studied human PET imaging data of participants of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to look for brain network changes and disease progression using the network neuroscience approach developed by Sporns. Veronese is also a co-author on the Alzheimer’s & Dementia journal article.
“Those two pieces of work led our team to develop tools that would extract additional meaning from images of MODEL-AD mouse models, with the goal of not only providing similar whole brain metrics observed in the previous clinical studies, but to also dive deeper and possibly understand how subnetworks within the brain of these models might shed light on the mechanisms of the underlying biology,” Territo said.
Chumin helped develop the tools and resources from the network neuroscience approach of human clinical research to preclinical animal models of MODEL-AD. The investigators analyzed the brain as a whole and also looked at subnetworks within the brain to see how those areas communicate and interact as the disease progresses.
“Using this approach, the research team’s analysis of metabolism changes in animal models confirmed previous clinical findings of disease progression in patients with Alzheimer’s disease,” Territo said.
The animal models showed age-related changes in glucose uptake as well as differences between males and females — similar to findings from Alzheimer’s disease human data.
Territo said MODEL-AD plans to use these network neuroscience tools in their investigations of other preclinical data, including models of late-onset Alzheimer’s disease, potential therapeutics for the disease and multi-modal analyses that combine neuroimaging data from PET and MRI.

Gun suicides increased from prepandemic rates in all racial and ethnic groups, but the degree of change differed drastically.The rate of suicides involving guns in the United States has reached the highest level since officials began tracking it more than 50 years ago, according to a new report from the Centers for Disease Control and Prevention.The rate increased by more than 10 percent in 2022 compared with 2019, and in some racial and ethnic groups, the rise was significantly steeper, especially among Native Americans. Overall, about 27,000 of 50,000 suicides were carried out by gun in 2022.Federal researchers involved in the analysis suggested that the coronavirus pandemic might have exacerbated many of the known risk factors for suicide generally, which include social isolation, strained relationships, and drug and alcohol disorders. At the same time, outside experts noted, the increased rates also correlated with another trend seen during the acute phase of the pandemic: rising gun sales.“When there are more firearms, there are more firearm suicides,” said Michael Anestis, the executive director of the New Jersey Gun Violence Research Center.The rate of suicide by any method has increased by one-third in the past two decades, according to federal data. More than half of those now involve firearms, the report said, a figure that translates to about one every 20 minutes.On the flip side, more than half of all gun deaths in the United States are suicides.To examine recent trends, federal researchers at the C.D.C.’s National Center for Injury Prevention and Control compiled and analyzed demographic and mortality data from the National Vital Statistics System and the Census Bureau. (Statistics from 2022, the most recent available data, are still considered preliminary.)They found that the firearm suicide rate in 2022 (8.1 per 100,000) was the highest level since at least 1968, the earliest year on record in the Centers for Disease Control and Prevention data.Suicide rates have increased across all racial and ethnic groups since 2019, but the degree of change differed drastically. American Indian and Alaska Native people, for example, saw the sharpest spike: a 66 percent increase in the rate of firearm suicides from 2019 to 2022 (to 10.6 from 6.4 per 100,000). The rate among Black people increased by 42 percent (to 5.3 from 3.8), and among Hispanic and Latino people by 28 percent (to 3.3 from 2.5). Asian and Pacific Island people saw firearm suicide rates increase by about 10 percent (to 1.9 from 1.7).White people experienced the smallest bump — a 9 percent increase since 2019 — but maintained the highest overall rate of firearm suicides (11.1 per 100,000 in 2022).Sarah Burd-Sharps, the senior director of research at Everytown for Gun Safety, a nonprofit group that aims to prevent gun violence, said the unparalleled increase in the rate among American Indian and Alaska Native communities could be caused by disparities in access to mental health care. She said the high levels of job loss and financial strains in Black and Latino communities during the pandemic could have contributed to the rise in those groups.Dr. Anestis of the New Jersey Gun Violence Research Center said he was “sadly not surprised,” since the demographic groups driving the surge in firearm sales did not match the stereotype of “older, white, male gun owners.” Research showed that about half of first-time buyers during the pandemic were female, and an increasing proportion were Black and Hispanic.Research shows that gun owners are no more likely than others to have suicidal thoughts, but surveys have showed that people who planned to purchase firearms during the pandemic were more likely to have thought recently about suicide than people without plans to purchase.“When firearms are going into new types of communities, and into homes where people have had the propensity to think about suicide, they are suddenly gaining access to the single most lethal method,” Dr. Anestis said.Researchers at the C.D.C. called for stronger efforts to reduce such suicides by addressing underlying inequities. Some states are working to develop safe options for storing guns away from a person’s home during times of distress.Dr. Anestis is planning a project that could train barbers, faith leaders, bartenders and even divorce lawyers on how to help promote those options to people who are discouraged, “much like knowing who’s going to hold your car keys when you’ve had too much to drink,” he said.“The goal is not to infringe upon their autonomy as an owner,” he said. “It’s to make sure that, in their worst moment, it’s not right there at their fingertips.”If you are having thoughts of suicide, call or text 988 to reach the 988 Suicide and Crisis Lifeline or go to SpeakingOfSuicide.com/resources for a list of additional resources. Go here for resources outside the United States.

The increased legalization of cannabis over the past several years can potentially increase its co-use with alcohol. Concerningly, very few studies have looked at the effects of these two drugs when used in combination. In a series of new studies, researchers at the University of Illinois Urbana-Champaign used rats to understand how brain structure and behavior can change when cannabis and alcohol are taken together.
Most researchers have studied the effects of either alcohol or THC (delta-9-tetrahydrocannabinol), the primary psychoactive drug in cannabis, alone. However, when people, especially adolescents, use these drugs, they often do so in tandem. Even when researchers study the co-use of these drugs, it involves injecting the animals with the drugs, which does not mirror what happens in humans.
“It’s rare that a person would have these drugs forced upon them. Also, other studies have shown that the effects of a drug are very different when an animal chooses to take it compared to when it is exposed against its will,” Lauren Carrica, a graduate student in the Gulley lab. “Our study is unique because the rats have access to both these drugs and they choose to consume them.”
The researchers used young male and female rats to mimic adolescence in humans. During feeding time, the animals were exposed to recreational doses (3 mg/kg-10 mg/kg) of THC that was coated on Fudge Brownie Goldfish Grahams and a sweetened 10% ethanol solution. The control group of rats were fed just the cookies and sweetened water in addition to their regular food.
“Training them to eat the drug was simple. We mimicked the timing that humans are more likely to take the drugs — at the end of the day. We did not deprive them of food or water. They were given an alcohol bottle in place of their water bottle during the access period and they preferred eating the cookies over their regular chow,” said Nu-Chu Liang, an associate professor of psychology.
After 20 days of increasing THC doses, rats were drug-free as they grew into young adulthood. The researchers took blood samples from the rats and also tested their memories to see if the co-use of drugs had any effect. Briefly, rats were required to remember the location of a target lever after a delay period that ranged from very short to very long. If they remembered the location, and pressed the target lever, they earned a food reward. If they responded on the wrong lever, no food was delivered.
“The effects were more pronounced in females and they had higher levels of chemicals that are produced when THC is broken down. Even so, the influence of THC on memory were modest,” Carrica said. “These volitional, low-to-moderate doses of alcohol, THC, or both drugs did not induce long lasting, serious cognitive defects.”
“The subtlety of these effects is not surprising because we have modeled how these drugs are taken in a social setting over a relatively short period of time,” said Joshua Gulley (GNDP), a professor of psychology. “Our results with the female rats are in agreement with other research that has shown that women who take edibles often have a different experience, which may be due to differences in how their bodies break down the drug.”

In this first study the researchers were unable to expose the rats to higher levels of THC because the rats would ignore the THC-laced cookies. “When you gave them higher doses, some animals lost interest in the cookies, and it is unclear why. It’s possible that they don’t like the higher doses or there is something about the taste or smell that becomes aversive,” Gulley said.
Although there were modest differences in behavior, the group still wanted to check whether anything had changed in the signaling pathways in the brain, especially at higher levels of THC. In the second paper they did so by injecting alcohol-drinking or non-drinking adolescent rats with THC doses ranging from 3 mg/kg to 20 mg/kg. Similar to the first study, the injections and alcohol drinking were then stopped and the rats were tested once they reached early adulthood.
Just like humans, rat brains undergo significant changes during adolescence, particularly in the prefrontal cortex, which helps them adapt to changing environments. The neurons in the prefrontal cortex modify their connections — a process referred to as synaptic plasticity — from the end of adolescence into young adulthood, according to Gulley.
The researchers wanted to test whether drug exposure during adolescence could change the ability of the brain to undergo synaptic plasticity as an adult. Therefore, they sacrificed the rats and measured the electrical signals generated in the brain.
“We found that alcohol and THC together significantly reduced, and in some cases prevented, the ability of the prefrontal cortex in drug-exposed rats to undergo plasticity in the same way that the brains from control animals can,” said Linyuan Shi, a graduate student in the Gulley lab. “The effects were apparent in rats exposed to either drug alone, and they were most pronounced with co-exposure to both drugs. We also found the impaired plasticity was likely due to changes in signaling caused by gamma-aminobutyric acid, a chemical messenger in the brain. When we used a chemical that enhances GABA, it could rescue the deficits we saw in the animals that had been exposed to the drugs.”
The researchers are now interested in understanding which neurons are involved in the response to the drugs. “From these studies, and the work our group has done with methamphetamine, we know that drug exposure during adolescence has the ability to disrupt cognitive functioning by altering the development of neuronal signaling in the prefrontal cortex. Although different drugs influence the brain in different ways, they might have the same effect on the brain that can manifest as cognitive disruptions later in life,” Gulley said. “Our ultimate goal is to harness our knowledge of these changes to develop treatment approaches for reversing cognitive dysfunctions that are associated with long-term drug use and addiction.”
The study “Effects of combined use of alcohol and delta-9-tetrahydrocannibinol on working memory in Long Evans rats” was published in Behavioural Brain Research.

The study “Effects of combined exposure to ethanol and delta-9-tetrahydrocannabinol during adolescence on synaptic plasticity in the prefrontal cortex of Long Evans rats” was published in Neuropharmacology.
Both works were supported by the National Institute on Drug Abuse.

Youth baseball players are prone to elbow pain and injuries, including repetitive overuse changes and fractures, based on the maturity of their bones, according to a new study being presented today at the annual meeting of the Radiological Society of North America (RSNA).
The repetitive motion and force of throwing a baseball places a large amount of stress on the growing bones, joints and muscles of the elbows of baseball players. Youth baseball players who have not yet reached skeletal maturity might be especially vulnerable to elbow pain and injuries.
“When we look at the forces that baseball players, even Little League baseball players, deal with during routine practice and games, it becomes apparent why elbow injuries are so common amongst this group,” said study co-author Vandan Patel, B.S., a radiology-orthopedics research scholar at Children’s Hospital of Philadelphia (CHOP) in Pennsylvania.
Most recent estimates show that 20 to 40% of youth baseball players between the ages of nine and 12 complain of elbow pain at least once during the season.
Skeletally immature children have growth plates, which are areas of bone that are made up of cartilage, a rubbery and flexible connective tissue, that allows the bones to grow and change in shape as a child ages. Growth plates are weaker than the surrounding muscles and bones and prone to injury that can lead to either reversible changes or permanent deformity.
Skeletal maturity occurs when the growth plates have closed, and no more bone (or growth) is being made. This usually occurs at the end of puberty, typically around age 13 to 15 for girls and 15 to 17 for boys.
In this retrospective study, the researchers reviewed elbow MRI exams from 130 youth players (18 years of age and younger) being evaluated for elbow pain. MRI is an ideal method for identifying joint problems, because it can non-invasively show cross-sectional details of soft tissues (cartilage, tendons and ligaments) and bone.

“We conducted this study in order to better understand the patterns of injuries that can occur among youth baseball players with elbow pain,” said senior author Jie C. Nguyen, M.D., M.S., director for the Section of Musculoskeletal Imaging in the Department of Radiology at CHOP. “Tissue vulnerability and, thus, sites at risk for injury, change with growth and maturation. A younger player injures differently than an older player. It is our hope that this data will help us continue to improve and individualize the care of current and future generations of youth baseball players.”
The average age of this study group of patients was 13.9 years, with 115 boys and 15 girls included. The frequency with which the patients played baseball varied from daily to recreationally.
Two radiologists independently reviewed the MRI exams to categorize the skeletal maturity and different findings of each patient’s elbow. They classified 85 patients as skeletally mature and 45 patients as skeletally immature.
The most common MRI findings in skeletally immature players included fluid build-up around the joint, stress injuries near the growth plate, fractures, and osteochondritis dissecans (OCD) lesions, where a piece of bone and the overlying cartilage is injured and can detach, leading to reduced range of motion and risk for premature osteoarthritis in adulthood.
Conversely, in skeletally mature players, the injury pattern shifts from the growth plates to the soft tissue. These players most often had triceps tendinosis — a condition in which the tendon connecting the triceps muscle to the elbow bone becomes strained, irritated or torn — and fluid build-up in the bony area of the elbow where the ulnar collateral ligament attaches. The ulnar collateral ligament runs on the inner side of the elbow and helps stabilize it.
Injuries that required surgery included intra-articular bodies (small fragments inside the joint), and unstable OCD.

“In terms of the skeletally immature children, 9 patients (11%) had intra-articular bodies, and 19 patients (22%) had OCD lesions,” Patel said.
The researchers hope that the results of this study will help to identify elbow injuries in children who play baseball and to individualize treatment based on skeletal maturity.
“This information is critically important not only to physicians, but also to parents and team coaches, all of whom provide crucial support for these children, reducing injury and preventing permanent damage on and off the field,” said co-author Theodore J. Ganley, M.D., director of Sports Medicine and Performance Center in the Division of Orthopaedics at CHOP. “As parents, caregivers and coaches, it is important to be aware of these findings in order to ensure that symptoms of pain are not overlooked during the baseball season.”
Although they did find that prevalence of injury was linked to prolonged play, the researchers said further studies are needed to identify exactly which injuries are more time dependent compared to others.
“This does not mean that elbow injuries are inevitable in baseball,” Patel said. “With proper technique and proper rest, these injuries could potentially be avoided.”
Additional co-authors are Shahwar M. Tariq, B.S., Liya Gendler, D.O., Apurva S. Shah, M.D., M.B.A., and Adam C. Zoga, M.D., M.B.A.

A new study estimates that the mortality burden attributable to air pollution from fossil fuel use is considerably higher than most previous estimates — a phaseout of fossil fuels would have tremendous, positive health outcomes.
Air pollution continues to be a leading public health risk. Previous estimates of the attributable mortality burden varied significantly between studies, primarily due to differences in the exposure-response relationships and the causes of death included. Furthermore, only a few global studies attributed mortality to specific air pollution sources. In a new study, the research team led by Jos Lelieveld and Andrea Pozzer from the Max Planck Institute for Chemistry and Andy Haines from the London School of Hygiene & Tropical Medicine assesses the consequences of a fossil fuel phaseout for disease-specific and all-cause mortality through the concomitant effects of air pollution.
The researchers find that most (52%) of the mortality burden is related to cardiometabolic conditions, particularly ischaemic heart disease that can cause heart attacks (30%). Stroke and chronic obstructive pulmonary disease both account for about 16%. About 20% is undefined, with arterial hypertension, diabetes mellitus, and neurodegenerative diseases possibly implicated.
“We estimate that 5.13 million excess deaths per year globally are attributable to ambient air pollution from fossil fuel use and therefore could potentially be avoided by phasing out fossil fuels,” states atmospheric chemist Jos Lelieveld, director at the Max Planck Institute for Chemistry. “This corresponds to 82% of the maximum number of air pollution deaths that could be averted by controlling all anthropogenic emissions.”
The new results were accomplished by applying a new relative risk model which optimizes the exposure-response relationship throughout the global range of ambient exposure levels. In addition, estimates of cause-specific and all-cause mortality due to long-term exposure to particulate matter (PM2.5) and ozone (O3) are attributed to pollution sources in this study.
Study design: Atmospheric modelling method distinguishes source categories The scientists developed a data-constrained global atmospheric modelling method to compute gaseous and particulate air pollutants and attributed them to source categories. The atmospheric model was used to calculate the fractional changes in PM2.5 related to emission sectors based on computer simulations in which source categories have been sequentially switched off.
“Our model calculated fractional changes were then applied to the high-resolution observational particulate pollution data to determine exposure reductions according to four emission scenarios,” explains Andrea Pozzer. The first scenario assumes that all fossil fuel-related emission sources are phased out. The second and third, “quarter way” and “half way” scenarios assume that 25 per cent and 50 per cent of the exposure reduction towards the fossil phaseout are realised, respectively. Finally, the fourth removes all anthropogenic sources for reference, thus only accounting for natural sources such as aeolian dust, marine and terrestrial biosphere emissions, and natural wildfires. Since the responses are not strongly non-linear, the team of scientists concludes that fossil fuel-related emission reductions at all levels of air pollution can decrease the number of attributable deaths substantially.

“Ambient air pollution would no longer be a leading environmental health risk factor if the use of fossil fuels were superseded by equitable access to clean sources of renewable energy,” emphasizes epidemiologist Andy Haines from the London School of Hygiene & Tropical Medicine. “This study provides new evidence to motivate rapid fossil fuel phaseout.” Phasing out fossil fuels is a remarkably effective health-improving and life-saving intervention and a major co-benefit of the United Nations’ goal of climate neutrality by 2050.
Air pollution continues to be a leading public health risk. Previous estimates of the attributable mortality burden varied significantly between studies, primarily due to differences in the exposure-response relationships and the causes of death included. Furthermore, only a few global studies attributed mortality to specific air pollution sources. In a new study, the research team led by Jos Lelieveld and Andrea Pozzer from the Max Planck Institute for Chemistry and Andy Haines from the London School of Hygiene & Tropical Medicine assesses the consequences of a fossil fuel phaseout for disease-specific and all-cause mortality through the concomitant effects of air pollution.
The researchers find that most (52%) of the mortality burden is related to cardiometabolic conditions, particularly ischaemic heart disease that can cause heart attacks (30%). Stroke and chronic obstructive pulmonary disease both account for about 16%. About 20% is undefined, with arterial hypertension, diabetes mellitus, and neurodegenerative diseases possibly implicated.
“We estimate that 5.13 million excess deaths per year globally are attributable to ambient air pollution from fossil fuel use and therefore could potentially be avoided by phasing out fossil fuels,” states atmospheric chemist Jos Lelieveld, director at the Max Planck Institute for Chemistry. “This corresponds to 82% of the maximum number of air pollution deaths that could be averted by controlling all anthropogenic emissions.”
The new results were accomplished by applying a new relative risk model which optimizes the exposure-response relationship throughout the global range of ambient exposure levels. In addition, estimates of cause-specific and all-cause mortality due to long-term exposure to particulate matter (PM2.5) and ozone (O3) are attributed to pollution sources in this study.
Study design: Atmospheric modelling method distinguishes source categories
The scientists developed a data-constrained global atmospheric modelling method to compute gaseous and particulate air pollutants and attributed them to source categories. The atmospheric model was used to calculate the fractional changes in PM2.5 related to emission sectors based on computer simulations in which source categories have been sequentially switched off.
“Our model calculated fractional changes were then applied to the high-resolution observational particulate pollution data to determine exposure reductions according to four emission scenarios,” explains Andrea Pozzer. The first scenario assumes that all fossil fuel-related emission sources are phased out. The second and third, “quarter way” and “half way” scenarios assume that 25 per cent and 50 per cent of the exposure reduction towards the fossil phaseout are realised, respectively. Finally, the fourth removes all anthropogenic sources for reference, thus only accounting for natural sources such as aeolian dust, marine and terrestrial biosphere emissions, and natural wildfires. Since the responses are not strongly non-linear, the team of scientists concludes that fossil fuel-related emission reductions at all levels of air pollution can decrease the number of attributable deaths substantially.
“Ambient air pollution would no longer be a leading environmental health risk factor if the use of fossil fuels were superseded by equitable access to clean sources of renewable energy,” emphasizes epidemiologist Andy Haines from the London School of Hygiene & Tropical Medicine. “This study provides new evidence to motivate rapid fossil fuel phaseout.” Phasing out fossil fuels is a remarkably effective health-improving and life-saving intervention and a major co-benefit of the United Nations’ goal of climate neutrality by 2050.