Publisher Health

Eating pheasant killed using lead shot is likely to expose consumers to raised levels of lead in their diet, even if the meat is carefully prepared to remove the shotgun pellets and the most damaged tissue.
A study has found that pheasants killed by lead shot contain many fragments of lead too small to detect by eye or touch, and too distant from the shot to be removed without throwing away a large proportion of otherwise useable meat.
Lead fragments often form when lead shotgun pellets hit the bodies of gamebirds. The fragments become lodged deep within the meat.
Researchers examined the carcasses of eight wild-shot common pheasants, killed on a farmland shoot using lead shotgun ammunition and on sale in a UK butcher’s shop. They found small lead fragments embedded in every pheasant, in addition to lead shotgun pellets in seven of them.
The researchers found up to 10mg of tiny lead shards per pheasant, all of which were much too small to be detected by eye or by touch.
Lead is toxic to humans when absorbed by the body — there is no known safe level of exposure. Lead accumulates in the body over time and can cause long-term harm, including increased risk of cardiovascular disease and kidney damage in adults. It is known to lower IQ in young children, and affect the neurological development of unborn babies.

Children who suffer a relapse of the aggressive cancer known as neuroblastoma have small chances of survival. However, a group including researchers at Karolinska Institutet in Sweden have now shown that DHODH blockers, which are well-tolerated in humans, can cure neuroblastoma in mice if administered in combination with chemotherapy. The study, published in the journal JCI Insight, paves the way for clinical trials of this combination therapy.
Neuroblastomas are tumours of nerve tissue that are typically diagnosed in very young children, normally before the age of two. The disease affects some 15 to 20 children in Sweden annually and is the deadliest form of cancer in infants. This new study shows that the protein DHODH (dihydroorotate dehydrogenase), which is involved in metabolism and DNA synthesis, also performs a key role in boosting the tumour growth of aggressive neuroblastomas.
“Through targeted treatment with specific DHODH blockers, we show in different cell and animal studies that cancer cells die, and that tumours stop growing,” says Ninib Baryawno, senior researcher at the Department of Women’s and Children’s Health, Karolinska Institutet, and one of the study’s corresponding authors. “This is very promising, as DHODH blockers have been shown to be well-tolerated in clinical trials for other disorders.”
Potential to improve survival
When the researchers combined DHODH blockers with a chemotherapy already in use for the treatment of children with neuroblastoma, they succeeded in curing mice with an aggressive variant of the disease.
“This combination therapy should be tested clinically as it has the potential to improve survival in children with neuroblastoma,” says Baryawno. “This is sorely needed since the chances of survival on relapse are unfortunately small with current treatments.”
The study was conducted in close collaboration with researchers at the Massachusetts General Hospital and the Harvard Stem Cell Institute in the USA. David Sykes, one of the senior authors in Boston, commented:

BOSTON – The structure of chromatin—the mixture of DNA and proteins that form chromosomes—can affect gene expression, and certain chromatin “readers” are important for monitoring this structure often in response to environmental cues.everse intestinal abnormalities in mice with inflammation characteristic of Crohn’s diseaseBOSTON – The structure of chromatin—the mixture of DNA and proteins that form chromosomes—can affect gene expression, and certain chromatin “readers” are important for monitoring this structure often in response to environmental cues.
Mutations within one such reader, called Speckled Protein 140 (SP140), are associated with an increased risk of certain immune diseases, including Crohn’s disease, a type of inflammatory bowel disease.
New research led by investigators at Massachusetts General Hospital (MGH) and published in Cell provides insights into the mechanisms behind this link, pointing to potential therapeutic targets.
SP140 expression is uniquely restricted to immune cells such as macrophages, which surround and kill microorganisms, remove dead cells, and stimulate the action of other immune cells.
Protein analyses by Kate L. Jeffrey, PhD, a principal investigator of immunology at MGH and an associate professor of medicine at Harvard Medical School, and her colleagues revealed that SP140 represses topoisomerases (TOP), which are enzymes that help DNA untangle during replication.
The team also found that in humans and mice, SP140 loss resulted in unleashed TOP activity, ultimately leading to defective gene expression and bacterial killing by macrophages that caused intestinal abnormalities. Inhibiting TOP rescued these defects in mice with inflammation characteristic of Crohn’s disease, a condition that remains incurable by surgical or therapeutic interventions.
“Applying a combination of human genetics, proteomics, biochemistry, utilization of primary immune cells from Crohn’s disease individuals, and in vivo animal studies, our study highlights the power of examining human disease associated genetic mutations to advance mechanistic understanding of disease,” says Jeffrey. “The work broadens our understanding of epigenetics in health—or the physical changes in cells’ DNA structure that affect the expression of genes in response to environmental cues. Importantly though, it revealed how dysregulation of epigenetic factors drive diseases such as Crohn’s that are rising in incidence because of the complex interplay of genes plus environment.”
Several TOP inhibitors are approved for the treatment of certain cancers, and many in the drug class are being tested in ongoing cancer clinical trials. These latest findings indicate that clinical trials should also test their effectiveness against Crohn’s disease.
Additional co-authors include Hajera Amatullah, Isabella Fraschilla, Sreehaas Digumarthi, Julie Huang, Fatemeh Adiliaghdam, Gracia Bonilla, Lai Ping Wong, Marie-Eve Rivard, Claudine Beauchamp, Virginie Mercier, Philippe Goyette, Ruslan I. Sadreyev, Robert M. Anthony, and John Rioux.
This study was supported by the Canadian Institutes of Health Research, the Canada Foundation for Innovation, the National Institutes of Health and the MGH Research Scholar Program. Dr. Jeffrey is a John Lawrence MGH Research Scholar 2020-2025.About the Massachusetts General HospitalMassachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In July 2022, Mass General was named #8 in the U.S. News & World Report list of “America’s Best Hospitals.” MGH is a founding member of the Mass General Brigham healthcare system.

More than six percent of Americans will develop posttraumatic stress disorder (PTSD) in their lifetime. This potentially chronic condition disrupts lives, and can lead to or exacerbate existing health issues such as depression, anxiety, eating disorders, and suicidal thoughts.
Despite the high prevalence of PTSD, the US Food and Drug Administration has only approved two medications to treat this condition — sertraline and paroxetine — and both have shown only limited effectiveness in reducing PTSD symptoms.
PTSD is also common among military veterans; more than 10 percent of US Department of Veterans Affairs (VA) patients experience these symptoms. Two years ago, researchers at Boston University School of Public Health (BUSPH) and the White River Junction Veterans Affairs Medical Center in Vermont began to investigate whether existing medications may improve PTSD symptoms, with funding from the National Institute of Mental Health.
During an initial exploratory analysis among a national cohort of VA patients, the researchers unexpectedly found that several new direct acting antiviral (DAA) medications used to treat hepatitis C virus infection were associated with PTSD symptom improvement. The findings were published in the journal Biological Psychiatry.
Now, in a new, follow-up study, the researchers have conducted a more rigorous analysis to examine and compare the effectiveness of the previously identified DAAs in PTSD symptom improvement. Their new analysis suggests the most promising DAA for prospective study as a potential medication for PTSD in patients without hepatitis C virus infection.
Published online ahead of print in the American Journal of Epidemiology, the new study found that the medication combination glecaprevir and pibrentasvir had the strongest association with PTSD symptom improvement among the DAAs most prescribed in the VA.

Researchers in the Smidt Heart Institute at Cedars-Sinai are one step closer to identifying patients at highest risk for developing sudden cardiac death — an electrical malfunction in the heart that causes it to stop beating.
To identify those at highest risk, researchers used a polygenic risk score that has been previously shown successful in predicting coronary artery disease. This Cedars-Sinai study, however, is the first study proven to be effective at identifying coronary artery disease patients at highest risk for sudden cardiac death.
The study, published today in the Journal of the American College of Cardiology, shows that patients with coronary artery disease without severely impaired heart function had the highest polygenic risk score, translating to a 77% increased risk for sudden cardiac death.
“In order to better predict and prevent sudden cardiac death, we must first understand the genetic connection between it and coronary artery disease,” said Roopinder Sandhu, MD, MPH, associate professor of Cardiology, and first author of the study. “We found incorporating information from this genetic risk score improved our ability to predict sudden death beyond the contributions of other known risk markers. Most exciting, the genetics were able to identify patients where sudden death was more likely to limit their life expectancy.”
Unlike heart attacks (myocardial infarctions), which are typically caused by clogged coronary arteries reducing blood flow to the heart muscle, sudden cardiac death most often results from the sudden onset of erratic electrical activity that impairs the pumping function of the heart. Patients may have little or no warning, and the disorder usually causes death within minutes if no resuscitation is performed.
Sudden cardiac death — also called sudden cardiac arrest — accounts for approximately 300,000 deaths each year in the U.S. and is a leading international health problem, responsible for 15% to 20% of all deaths. Coronary artery disease is the most common underlying reason for sudden cardiac death. Sandhu says in the future, this work may help better identify patients who would benefit most from lifesaving therapies like a defibrillator.
At present, most sudden cardiac deaths — 70% — occur in patients who do not meet current guidelines for prevention with defibrillator therapy. Thus, contemporary practice not only neglects most individuals who develop sudden cardiac deathbut also involves electrophysiologists placing defibrillators in patients with advanced heart disease who are often unlikely to benefit due to limited life expectancy.
The JACC study is based on data from the National Institutes of Health-sponsored PRE-DETERMINE observational study, which has aimed to more accurately identify people at risk for sudden cardiac death among the larger pool of coronary artery disease patients who do not have advanced heart disease.
Christine Albert, MD, MPH, chair of the Department of Cardiology in the Smidt Heart Institute and senior author, said, “This study indicates there is opportunity to identify patients at highest risk for sudden cardiac death, and then offering meaningful, preventative treatment solutions like a defibrillator. Based on our pivotal research, we now have the foundation to achieve this.”
Funding: PREDETERMINE was supported by research grants from the National Heart, Lung, and Blood Institute R01HL091069, St. Jude Medical Inc., and St. Jude Medical Foundation (to CMA). Genetic analysis was supported by grants 1K08HG010155 and 1U01HG011719 (to A.V.K.) from the National Human Genome Research Institute.
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Materials provided by Cedars-Sinai Medical Center. Note: Content may be edited for style and length.

The UK Government’s current proposal to fortify one type of flour with folic acid is inadequate as it suggests a low dose that would fail to prevent hundreds of cases of severe birth defects each year, according to a new paper by UCL’s Professor Sir Nicholas Wald.
The article, published in The Journal of Medical Screening, argued that increasing the dose from what is currently proposed would prevent about 80% of neural tube defects, which result in life-threatening and disabling spinal conditions such as spina bifida and anencephaly. The currently proposed policy would only prevent about 10%.
The neural tube forms the early part of the brain and spine within the first 4 weeks of gestation, usually before the mother knows she is pregnant. A deficiency in folate, or vitamin B9, can cause defects in the neural tube. Folic acid is the synthetic and stable form of folate. While women are advised to take folic acid supplements prior to and during the early part of pregnancy, many mothers do not take the supplement early enough.
Last September the UK Government announced plans to fortify non-wholemeal flour with folic acid to better prevent neural tube defects, joining about 80 countries around the world who already do this.
The author of the new paper, Professor Wald (UCL Institute of Health Informatics), led the international trial (the MRC Vitamin Study) that over 30 years ago definitively established folate deficiency as a cause of neural tube defects. He said: “Mandatory fortification of flour with folic acid has the potential to greatly reduce the number of disabilities and early deaths caused by neural tube defects. However, what is currently proposed is only a token level of fortification. It does not make sense to implement a policy preventing only 10% of neural tube defects when 80% could be safely prevented simply by increasing the level of fortification and extending it to wholemeal flour and grains.
“The UK has a chance to lead the world in preventing neural tube defects through fully effective fortification, as no country currently fortifies flour at a level that is proven to be most effective.”
In the paper, Professor Wald noted that there had been concerns that a higher dose of folic acid could be neurotoxic, but these were misplaced, he said, as they were based on a study later found to be flawed. Another concern was that larger doses of folic acid might conceal signs of a different vitamin deficiency (B12 deficiency), but this concern is outdated, the paper said, as tests could now diagnose B12 deficiency in symptomatic patients early enough for effective B12 treatments to be given.

The deadliest form of brain cancer returns because tumours adapt to treatment by recruiting help from nearby healthy tissue, say researchers who are trying to find a cure for the disease.
A new study, by a global team including University of Leeds experts, has found that in response to treatment, high-grade gliomas appear to remodel the surrounding brain environment, potentially creating interactions with nearby neurons and immune cells in ways that protect the tumour cells and hide them from the body’s defences.
The team also found that lower grade tumours often develop a new mutation that allows the cells to start dividing more rapidly, potentially catapulting them into a higher-grade form.
Glioma brain tumours are rare, but a diagnosis is devastating because there is currently no cure. Low-grade gliomas have a better survival rate than, but often progress to high-grade gliomas. More than 90% of patients with high-grade tumours die within five years.
Current treatments include surgery, radiation therapy and chemotherapy. The findings indicate that new drugs are needed to supplement these.
Dr Lucy Stead, Associate Professor of Brain Cancer Biology in the University of Leeds’ School of Medicine, and the lead UK academic for the study, said: “The brain is a hugely complex organ made up of lots of different types of cells, and brain tumours are equally diverse and complicated.

Although many people with dietary allergies experience mild symptoms when exposed to triggering foods, some face potentially fatal consequences. A bacterial compound called butyrate that’s made by healthy microbiomes has shown promise against allergic reactions in lab tests, but it’s nasty to take orally. Today, scientists describe a more palatable way to deliver this compound and report that their “polymeric micelles” are effective against peanut allergies in mice. The treatment could someday counteract many types of food allergies and inflammatory diseases.
The researchers will present their results at the fall meeting of the American Chemical Society (ACS).
Some of the bacteria in the gut microbiome produce metabolites, such as butyrate, that foster the growth of beneficial bacteria and maintain the lining of the gut. If a person’s microbiome is unhealthy and lacks these butyrate-producing bacteria, fragments of partially digested food can leak out of the gut and produce an immune reaction that results in an allergic response.
One way to treat those with allergies would be to provide the missing bugs to them orally or with a fecal transplant, but that hasn’t worked well in the clinic, according to Jeffrey Hubbell, Ph.D., one of the project’s principal investigators (PIs). “So we thought, why don’t we just deliver the metabolites — like butyrate — that a healthy microbiome produces?”
“But butyrate has a very bad smell, like dog poop and rancid butter, and it also tastes bad, so people wouldn’t want to swallow it,” says Shijie Cao, Ph.D., who is presenting the results at the meeting for the team, which is at the University of Chicago. And even if people could choke it down, butyrate would be digested before reaching its destination in the lower gut.
To overcome these challenges, the researchers, including co-PI Cathryn Nagler, Ph.D., and Ruyi Wang, Ph.D., designed a new delivery system. They polymerized butanoyloxyethyl methacrylamide — which has a butyrate group as a side chain — with methacrylic acid or hydroxypropyl methacrylamide. The resulting polymers self-assembled into aggregates, or polymeric micelles, that tucked the butyrate side chains in their core, thus cloaking the compound’s foul smell and taste.
The researchers administered these micelles to the digestive systems of mice lacking either healthy gut bacteria or a properly functioning gut lining. After digestive juices released the butyrate in the lower gut, the inert polymers were eliminated in the feces. The treatment restored the gut’s protective barrier and microbiome, in part by increasing production of peptides that kill off harmful bacteria, which made room for butyrate-producing bacteria.
Most importantly, dosing allergic mice with the micelles prevented a life-threatening anaphylactic response when they were exposed to peanuts. “This type of therapy is not antigen specific,” Cao notes. “So theoretically, it can be broadly applied to any food allergies through the modulation of gut health.”
Next up are trials in larger animals, followed by clinical trials. If those trials succeed and the U.S. Food and Drug Administration approves the oral treatment, the micelles could be marketed in small packets; consumers would tear open a packet and stir the contents into a glass of water or juice. In other work with the micelles, the team is analyzing data on treating inflammatory bowel diseases with the oral therapy.
The team is also investigating administration via injection. The researchers have shown that this method allows the micelles and their butyrate cargo to accumulate in lymph nodes, which are part of the immune system. They found that this approach is effective in treating peanut allergies in mice, but it could also be used to suppress immune activation locally — rather than throughout the body. For example, injections could be helpful in patients who have had an organ transplant or who have a localized autoimmune and inflammatory condition, such as rheumatoid arthritis.
The researchers acknowledge support and funding from their start-up company, ClostraBio, and the University of Chicago.

Lithium can alleviate the symptoms of bipolar disorder and depression — if taken in just the right amount. Too little won’t work, while too much can bring on dangerous side effects. To precisely monitor the amount of this medication in the body, patients must undergo invasive blood tests. But today, scientists report the invention of a tiny sensor that detects lithium levels from sweat on the surface of a fingertip in as little as 30 seconds, without a trip to the clinic.
The researchers will present their results today at the fall meeting of the American Chemical Society (ACS).
Not only must lithium be taken at a certain dosage, but patients often struggle to take it as prescribed and may miss pills. So, when the medication doesn’t appear to be working, health care providers need to know how much medication the patient is actually swallowing. But current options for monitoring have significant drawbacks. For example, blood draws produce accurate results, but they are invasive and time consuming. Pill counters, meanwhile, don’t directly measure the intake of the medication. To address these limitations, the team turned to another body fluid.
“Although it may not be visible, the human body constantly produces sweat, often only in very small amounts,” says Shuyu Lin, Ph.D., a postgraduate student researcher who is co-presenting the work with graduate student Jialun Zhu at the meeting. “Small molecules derived from medication, including lithium, show up in that sweat. We recognized this as an opportunity to develop a new type of sensor that would detect these molecules.”
“Through a single touch, our new device can obtain clinically useful molecular-level information about what is circulating in the body,” says Sam Emaminejad, Ph.D., the project’s principal investigator, who is at the University of California, Los Angeles (UCLA). “We already interact with a lot of touch-based electronics, such as smart phones and keyboards, so this sensor could integrate seamlessly into daily life.”
Devising a sensor to detect lithium presented some technical challenges, however. Sweat is generally only present in minute amounts, but the electrochemical sensing needed to detect charged particles of lithium required an aqueous, or watery, environment. To provide it, the team engineered a water-based gel containing glycerol. This extra ingredient prevented the gel from drying out and created a controlled environment for the electronic portion of the sensor.
To trap the lithium ions after they traversed the gel, the team used an ion-selective electrode. The accumulating ions generate a difference in electrical potential compared with a reference electrode. The researchers used this difference to infer the concentration of lithium present in sweat. Together, these components comprise a tiny, rectangular sensor that is smaller than the head of a thumbtack and can detect lithium in about 30 seconds. The sensor is still in the preliminary testing phase, but ultimately, the researchers envision incorporating it into a larger, yet-to-be designed system that provides visual feedback to the provider or the patient.
After characterizing the sensor using an artificial fingertip, the team recruited real people to test it, including one person on a lithium treatment regimen. The researchers recorded this person’s lithium levels before and after taking the medication. They found that these measurements fell close to those derived from saliva, which prior research has shown to accurately measure lithium levels. In the future, the researchers plan to study the effects of lotion and other skin products on the sensor’s readings.
This technology also has applications beyond lithium. Emaminejad is developing similar touch-based sensors to monitor alcohol and acetaminophen, a painkiller also known as Tylenol®, while also exploring the possibility of detecting other substances. The complete sensing systems could include additional features, such as encryption secured by a fingerprint, or, for substances prone to abuse, a robotic dispensing system that releases medication only if the patient has a low level in their bloodstream.
The researchers acknowledge support and funding from the National Science Foundation, Brain and Behavior Foundation, Precise Advanced Technologies and Health Systems for Underserved Populations and the UCLA Henry Samueli School of Engineering and Applied Sciences.

Marijuana and hallucinogen use in the past year reported by young adults 19 to 30 years old increased significantly in 2021 compared to five and 10 years ago, reaching historic highs in this age group since 1988, according to the Monitoring the Future (MTF) panel study. Rates of past-month nicotine vaping, which have been gradually increasing in young adults for the past four years, also continued their general upward trend in 2021, despite leveling off in 2020. Past-month marijuana vaping, which had significantly decreased in 2020, rebounded to pre-pandemic levels in 2021.
Alcohol remains the most used substance among adults in the study, though past-year, past-month, and daily drinking have been decreasing over the past decade. Binge drinking (five or more drinks in a row in the past two weeks) rebounded in 2021 from a historic low in 2020, during the early stages of COVID-19 pandemic. On the other hand, high-intensity drinking (having 10 or more drinks in a row in the past two weeks) has been steadily increasing over the past decade and in 2021 reached its highest level ever recorded since first measured in 2005.
“As the drug landscape shifts over time, this data provides a window into the substances and patterns of use favored by young adults. We need to know more about how young adults are using drugs like marijuana and hallucinogens, and the health effects that result from consuming different potencies and forms of these substances,” said National Institute on Drug Abuse Director Nora Volkow, M.D. “Young adults are in a critical life stage and honing their ability to make informed choices. Understanding how substance use can impact the formative choices in young adulthood is critical to help position the new generations for success.”
Since 1975, the Monitoring the Future study (https://nida.nih.gov/research-topics/trends-statistics/monitoring-future) has annually surveyed substance use behaviors and attitudes among a nationally representative sample of teens. A longitudinal panel study component of MTF conducts follow-up surveys on a subset of these participants to track their drug use through adulthood. Participants self-report their drug use behaviors across three primary time periods — lifetime, past year (12 months), and past month (30 days). The MTF study is conducted by scientists at the University of Michigan’s Institute for Social Research, Ann Arbor, and is funded by NIDA, part of the National Institutes of Health.
Data for the 2021 survey were collected online from April 2021 through October 2021. Key findings in the young adult group include:
Marijuana Use: Past-year, past-month, and daily marijuana use (use on 20 or more occasions in the past 30 days) reached the highest levels ever recorded since these trends were first monitored in 1988. The proportion of young adults who reported past-year marijuana use reached 43% in 2021, a significant increase from 34% five years ago (2016) and 29% 10 years ago (2011). Marijuana use in the past month was reported by 29% of young adults in 2021, compared to 21% in 2016 and 17% in 2011. Daily marijuana use also significantly increased during these time periods, reported by 11% of young adults in 2021, compared to 8% in 2016 and 6% in 2011.