Publisher Health

In newly disclosed documents, federal researchers find that cannabis may have medical uses and is less likely to cause harm than drugs like heroin.Marijuana is neither as risky nor as prone to abuse as other tightly controlled substances and has potential medical benefits, and therefore should be removed from the nation’s most restrictive category of drugs, federal scientists have concluded.The recommendations are contained in a 250-page scientific review provided to Matthew Zorn, a Texas lawyer who sued Health and Human Services officials for its release and published it online on Friday night. An H.H.S. official confirmed the authenticity of the document.The records shed light for the first time on the thinking of federal health officials who are pondering a momentous change. The agencies involved have not publicly commented on the their debates over what amounts to a decriminalization of marijuana at the federal level.Since 1970, marijuana has been considered a so-called Schedule I drug, a category that also includes heroin. Schedule I drugs have no medical use and a high potential for abuse, and they carry severe criminal penalties under federal trafficking laws.The documents show that scientists at the Food and Drug Administration and the National Institute on Drug Abuse have recommended that the Drug Enforcement Administration make marijuana a Schedule III drug, alongside the likes of ketamine and testosterone, which are available by prescription.The review by federal scientists found that even though marijuana is the most frequently abused illicit drug, “it does not produce serious outcomes compared to drugs in Schedules I or II.”We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? 

Elite soccer didn’t always welcome players’ requests for help. Scandals, attitudes and support programs are changing that.The one thing she could not do, Sinead Farrelly knew, was talk. Nobody had ever told her that explicitly, of course. It was just something she understood. Soccer, her first time around, operated under what she can now call a “culture of silence.”The perceived delicacy of the sport meant that principle applied publicly almost as a matter of policy. Only a little more than a decade ago, Farrelly and her peers playing in professional leagues — first the W.P.S. and then, after its dissolution, the incipient N.W.S.L — did so keenly aware of their own mortality.“You want fans to come so the league can survive,” Farrelly said. “You can’t be sharing how bad it is or what the conditions are really like. You have to put on a show for the development of sport. You owe it to yourself, your teammates, future generations.” It felt, to her, like “living a double life.”Something darker held the omertà in place privately, among the players themselves. Years later, Farrelly would feel strong enough to tell the world what she had endured: years of psychological torment and allegations of coercive sex at the hands of the coach to whom she felt she owed her career.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? 

A research group at Nagoya University in Japan has developed a new catalyst that promises to revolutionize the asymmetric synthesis of pharmaceuticals called chiral macrocyclic dilithium(I) salt. It overcomes the lack of reactivity of ketones and the difficulty inducing them to arrange atoms, which are common challenges in drug-making. The researchers used their technique to synthesize a key intermediate of the incontinence drug oxybutynin. Their catalyst promises to contribute to future drug discovery and development. They published their results in the Journal of the American Chemical Society.
“This research represents a major advance in chiral drug synthesis,” said Professor Ishihara from Nagoya University. “Our catalyst can facilitate the rapid synthesis of complex compounds. This holds great promise for future drug discovery efforts.”
All drugs are made from precursor chemicals. Ideal precursors are versatile compounds that can create a wide variety of end products. One particularly versatile precursor is optically active tertiary propargyl alcohol. It is used to create pharmaceuticals, including anticancer agents, antibiotics, and antivirals. However, production of these important chemicals is hindered by the low reactivity of ketones, which are precursors of tertiary propargyl alcohols. In addition, there is the difficulty of their asymmetric induction, a process that favors the creation of a specific arrangement of atoms that is more suitable than other arrangements for making the drug.
To overcome the low reactivity of the ketones, highly reactive lithium-based reactants, called lithium acetylides, are added. However, their reactivity is often insufficient for use with ketones. The development of a new catalyst was needed to promote the reaction and control the selection of the optimal arrangement of atoms.
Enzymes are ideal for these reactions, as they lower the energy required to make the reaction occur. However, due to their large and complicated structure, the synthesis of enzymes is difficult. The currently used acyclic dilithium catalyst-based approach was pioneered by Kumamoto University’s Makoto Nakajima. However, this approach has a limited substrate scope due to the self-aggregation of catalysts and an overly long reaction time of up to 12 hours. This creates a bottleneck when producing the desired drug.
Professor Kazuaki Ishihara and his collaborators, which included his graduate students, developed a chiral macrocyclic dilithium(I) salt. It is a simple catalyst that functions like an enzyme, overcoming the decrease in reactivity by activating less reactive ketones. This allows the addition of acetylides, such as lithium acetylides. The large macrocyclic structure of the catalyst allows them to catalyze even bulky ketones. This prevents aggregation between the catalyst and the lithium-based reactants.
Despite being simpler than enzymes, the researchers found that their catalyst was more efficient than other known catalysts. They successfully synthesized optically active tertiary propargyl alcohol from a variety of ketones. Although this industrial alcohol is difficult to produce by conventional methods, they synthesized it in 5 to 30 minutes. This is much faster than the 12 hours that Nakajima’s catalyst-based production process takes.
The addition of alkynyls to carbonyl compounds, such as ketones, is a valuable synthetic method for the preparation of versatile chiral alcohols that are widely found in pharmaceuticals and natural products. This research is a breakthrough in modern synthetic organic chemistry and a promising leap forward in drug discovery.

A new study by researchers at University of Limerick in Ireland has found high rates of anaemia among patients in the Irish health system, while screening for common causes was found to be low.
The research study carried out by a team at University of Limerick School of Medicine found that substantial numbers of men and women in the health system had anaemia, the presence of which is strongly associated with high rates of hospitalisation, death, and poor quality of life.
Anaemia (a low level of haemoglobin in the body) is a common but treatable condition that predicts adverse clinical outcomes. It affects nearly two billion people across the globe and is the third-leading cause of years with lived disability in the world.
While the study revealed a high burden of patients with the condition, it found that there were relatively low rates of screening for treatable causes of anaemia, including deficiencies in vitamin B12, folate, and iron, which highlights an important gap in care delivery programs and emphasises the need for quality improvement initiatives.
Prior to the large population-based study, the prevalence of anaemia and information on its underlying causes was largely unknown as data at the national or regional level was limited.
The research, published in the journal BJGP Open, is the largest study ever to explore the burden of anaemia and the extent of investigation for underlying common causes in Ireland.
The study found that 12% of Irish patients had anaemia with 1 in 8 women (13.2%) affected and 1 in 10 men (10.5%). Most of these patients were found to have had mild anaemia (9.1% of total), with moderate to severe anaemia present in the remaining 2.9%.

The percentage of patients with anaemia was particularly high in elderly patients, and in patients with underlying medical conditions such as kidney disease, diabetes and for patients undergoing treatment in specific clinical settings.
Despite the high burden of anaemia, less than 20% of anaemic patients were tested for deficiencies of vitamin B12 and folic acid, and only one third of all patients were screened for iron deficiency during follow-up.
Although there was some improvement in screening rates with increasing severity of anaemia, approximately 50% of patients with severe anaemia did not undergo screening.
“This is the largest study to address the magnitude of anaemia and the extent to which it is investigated in the Irish health system,” according to senior investigator Professor Austin Stack, Foundation Chair of Medicine at UL’s School of Medicine and Consultant Nephrologist, University Hospital Limerick.
“Our study reveals a significant burden of anaemia that was present in several high-risk groups, including patients with diabetes, chronic kidney disease, and the elderly. The prevalence of anaemia increased exponentially in older men and women, highlighting their increased vulnerability.
“Patients with advanced kidney disease had nearly eight-fold higher prevalence compared to patients with normal kidney function. Patients who attended the emergency room, outpatient departments or admitted to hospital were found to be particularly affected, with prevalence ranging from 18 % to 29 %,” Professor Stack explained.

Anaemia is a condition in which the body does not have enough healthy red blood cells or haemoglobin (an iron-rich protein) to carry oxygen to the cells around the body.
Haemoglobin is essential for red blood cells to carry oxygen from the lungs to the rest of the body. When someone suffers from anaemia, the body does not get enough oxygen in the blood, and this can cause tiredness, shortness of breath, and dizziness.
The researchers assembled a cohort of 112,181 patients using data from the National Kidney Disease Surveillance System to assess for anaemia and followed them for up to one year to explore the use of screening tests that check for iron deficiency, B12, and folate deficiency.
Co-author Dr Leonard Browne, Senior Research Fellow in Biostatistics at the UL School of Medicine, highlighted the low level of screening for treatable causes of anaemia.
“What is remarkable is that less than 20% of anaemic patients were screened for vitamin B12 and folate deficiency, and only one third were screened for iron deficiency at three-months follow-up,” he explained.
“Despite some improvement with increasing severity of anaemia, approximately 50% of patients with severe anaemia did not undergo screening. Indeed, when we followed patients for up to 12 months, screening rates did increase although modestly for B12 and folate deficiency — 30% — and doubled for iron deficiency — 46%. These findings reveal that common causes of anaemia are inadequately tested for in the wider health system especially among high-risk groups.”
Professor Stack emphasised the importance of screening for and identifying the underlying cause of anaemia.
“We found that one in three patients had evidence of absolute iron deficiency, 6.3% had B12 deficiency, and a further 5.8% were folate deficient. All these deficiencies are easily treated in modern day clinical practice leading to significant improvement in the degree of anaemia. This study provides a valuable starting point from which we can begin to understand practice patterns in care delivery and the development of quality improvement programmes in the health system.
“Iron deficiency is the main cause of anaemia affecting women more than men. The findings from our study correlate well with the international body of evidence, which shows that investigation of anaemia subtype is uncommon and that the standards of anaemia management vary considerably,” Professor Stack added.
The research was funded by the Health Research Board (HRB) and Dr Mairéad O’Driscoll, Chief Executive of the HRB said: “Professor Stack’s research is a really nice example of how intelligent and targeted secondary-data analysis can make important contributions to our knowledge base. The data-driven insights from his work have obvious potential to inform and improve health service delivery.
“The HRB is committed to working with all of our partners to advance the use of primary and secondary data to enhance health policy, to improve healthcare delivery and to drive innovation in our health services.”

Researchers from the University of Pennsylvania have discovered key insights into the molecular basis of skin color variations among African populations. Their findings, published in Nature Genetics, broaden the understanding of human evolution and the genetics underpinning contemporary human skin color diversity.
“Despite the abundant genetic diversity within African populations, they have been historically underrepresented in genetic studies,” says senior author Sarah Tishkoff, a Penn Integrates Knowledge University Professor with appointments in the Perelman School of Medicine and School of Arts & Sciences. “Our findings offer novel information about the genetic basis and evolutionary history of skin color diversity, contributing to a clearer depiction of human evolution.”
The story of human evolution is as rich and diverse as the adaptations found across the world’s populations, Tishkoff says. She notes that, among many adaptive traits, skin color stands out as one of the most well-known. Darker skin tones, prevalent in equatorial regions, serve as nature’s very own sunblock, evolving over millennia to shield these populations from the sun’s intense ultraviolet radiation. Conversely, lighter pigmentation, as seen in populations closer to the poles, is an adaptation to mitigate the risks of insufficient sun exposure by maximizing vitamin D production, which is triggered by UV exposure.
“Our approach involved genome-wide association studies of skin color from more than 1,500 eastern and southern African individuals as well as scanning the genome to identify genetic variants that are highly differentiated between lightly-pigmented Khoesan-speaking San population and other darkly pigmented Africans and may play a role in local adaptation in that population,” says Yuanqing Feng, first author of the paper and a postdoctoral researcher in the Tishkoff Lab.
The researchers note that pigmentation is a complex trait influenced by hundreds of variants scattered across the genome, with the majority situated in noncoding regions. These noncoding variants may affect the expression of genes located up to one million bases away. The vast number of mutations associated with skin color and the uncertainty surrounding the target genes regulated by these mutations make it particularly arduous for researchers to find the precise genetic mechanisms governing this trait.
Feng and collaborators used massively parallel reporter assays to discern the regulatory activities of thousands of variants. This high-throughput technique narrowed down the thousands of candidates to 165 functional variants. To identify the target genes of these functional variants, Feng further constructed high-resolution chromatin interaction maps in melanocytic cells using chromatin conformation capture assays. “This is a high-resolution 3D genome map in melanoma cells that will be valuable for gene regulation studies in pigmentation and melanoma biology,” Feng says.
Using CRISPR/Cas9-based genome editing, the researchers discovered that mutations in an enhancer of OCA2, a gene associated with albinism, could lead to a 75% reduction in melanin levels when compared to control cells. Within the same OCA2 enhancer, the researchers identified two closely located regulatory variants, estimated to be 1.2 million years old and 57 thousand years old, with the latter coinciding with the period of human migration from Africa.

“This case illustrates the continuous evolution of human skin color, and it’s remarkable to observe the significant effects on skin pigmentation attributed to a single enhancer,” Feng says.
San people have relatively lighter pigmentation compared to other African populations and possess the oldest genetic lineages in humans. While it is hypothesized that the light skin color of the San may result from adaptation to a southern African environment, the genetic underpinnings of this adaptation remain elusive. The researchers pinpointed several crucial regulatory variants near MITF, LEF1, and TRPS1 that contribute to the skin color adaptation observed in the San.
“MITF, LEF1, and TRPS1 are involved in signaling pathways regulating both melanocyte differentiation and hair development,” Tishkoff says. “This suggests that the variants influencing the lighter skin pigmentation observed in the San people may also contribute to their distinctive hair morphology.” Notably, the variant near TRPS1 associated with lighter skin color is at nearly 100% frequency in the San and in most non-Africans, whereas the variant associated with darker skin color is common in most other African populations and in the darkly pigmented Melanesian population, a striking example of global adaptations to UV exposure.”
Additionally, the researchers found a novel gene impacting human skin pigmentation, CYB561A3, which regulates iron homeostasis and influences melanin levels in melanocytic cells. “To our knowledge, the role of CYB561A3 in skin pigmentation has not been reported before. Intriguingly, there have been reports linking intravenous iron infusion to skin hyperpigmentation. Given that CYB561A3 encodes an iron reductase, I am curious about the role of this protein in this process,” Tishkoff says.
“Our findings underscore the complexity of genetic factors influencing skin color and the benefits of including ethnically diverse and underrepresented populations in genetic studies,” she says. “Conducting functional studies on the impact of noncoding variants will enhance our comprehension of the genetics underlying complex human traits and disease risk.”
“The populations included in this study are from remote regions of Africa and required the use of a mobile lab set up in the field sites,” Tishkoff says. “The collaboration with our partners in Africa was key to the success of this research project.”
In future research, the Tishkoff lab would like to use its innovative functional genomics approach to identify more genetic variants contributing to human pigmentation and other adaptive traits in a larger sample of ethnically diverse Africans.

Sarah Tishkoff is the David and Lyn Silfen University Professor in Genetics and Biology and a Penn Integrates Knowledge University Professor with appointments in the Perelman School of Medicine’s Department of Genetics and Department of Medicine and in the School of Arts & Sciences’ Department of Biology at the University of Pennsylvania.
Yuanqing Feng is a postdoctoral fellow in the Tishkoff lab at Penn.
Other authors include Ning Xie, Chao Zhang, Fang Zhang, and Matthew E.B. Hansen of Penn; Fumitaka Inoue of Kyoto University; Shaohua Fan of Fudan University; Thomas Nyambo of Hubert Kairuki Memorial University; Sununguko Wata Mpoloka and Gaonyadiwe George Mokone of the University of Botswana; Charles Fokunang and Alfred K. Njamnshi of the University of Yaoundé; Gurja Belay of Addis Ababa University; Michael S. Marks of the Children’s Hospital of Philadelphia Research Institute; Elena Oancea of Brown University; and Nadav Ahituv of the University of California, San Francisco.
This research was supported by the National Institutes of Health (grants R35GM134957-01, 3UM1HG009408-02S1, 1R01GM113657-01, 5R01AR076241-02, and 1S10OD010786-01) and the Penn Skin Biology and Disease Resource-based Center (Grant NIH P30-AR069589).

For the first time, researchers have analysed the impact of antibiotic use on the rise of treatment-resistant bacteria over the last 20 years in the UK and Norway. They show that while the increase in drug use has amplified the spread of superbugs, it is not the only driver.
Researchers from the Wellcome Sanger Institute, the University of Oslo, the University of Cambridge, and collaborators, conducted a high-resolution genetic comparison of bacteria. They compared over 700 new blood samples with nearly 5,000 previously sequenced bacterial samples to answer questions about what factors influence the spread of antibiotic-resistant Escherichia coli (E. coli).
The study, published today (11 January) in the Lancet Microbe, shows that greater antibiotic use does drive an increase in treatment-resistant bacteria in some instances. However, researchers confirmed that this varies depending on the type of broad-spectrum antibiotic used. They also found that the success of antibiotic-resistance genes depends on the genetic makeup of the bacteria carrying them.
Recognising all the main factors behind antibiotic resistance can help build a deeper knowledge of how these bacteria spread and what hinders them. This could then better inform public health interventions that use a complete view of the environment to help stop the spread of treatment-resistant infections.
The bacterium, E. coli is a common cause of bloodstream infections worldwide.1 The type of E. coli responsible for these infections is commonly found in the gut, where it does not cause harm. However, if it gets into the bloodstream due to a weakened immune system it can cause severe and life threatening infections.
As an added challenge for healthcare providers, antibiotic resistance, in particular multi-drug resistance (MDR), has become a frequent feature of such infections. In the UK, over 40 per cent of E. coli bloodstream infections are resistant to a key antibiotic used in the treatment of serious infections in hospital.2
Rates of antibiotic resistance in E. coli vary globally. For example, the rate of resistance to a different antibiotic, one commonly used to treat urinary tract infections caused by E. coli, ranged from 8.4 per cent to 92.9 per cent depending on the country.3
Antibiotic resistance has been a topic of research for decades, and the surveillance data from previous studies have consistently shown an association between antibiotic use and an increased frequency of MDR in bacteria worldwide, including in the UK.

Previous studies have suggested a stable coexistence of resistant and non-resistant E. coli strains and in some cases, the non-resistant bacteria are more successful. However, previously it was not possible to assess the role of the genetic drivers of this due to the lack of unbiased large-scale longitudinal data sets.
This new study, from the Wellcome Sanger Institute, the University of Oslo, and collaborators, is the first time it has been possible to directly compare the success of the different strains of E. coli between two countries — Norway and the UK — and explain differences based on country-wide antibiotic usage levels.
By analysing data that spanned almost 20 years, they found that the use of antibiotics was linked to increased resistance in some instances, depending on the type of antibiotic. One class of antibiotics, non-penicillin beta-lactams, were used three to five times more on average per person in the UK compared to Norway. This has led to a higher incidence of infections by a certain multi-drug resistant E. coli strain.
However, the UK also uses the antibiotic trimethoprim more often, but analysis did not uncover higher levels of resistance in the UK when comparing the common E. coli strains found in both countries.
The study found that the survival of MDR bacteria depended on what strains of E. coli were in the surrounding environment. Due to this and other selective pressures in an area, researchers concluded that it is not possible to assume that the widespread use of one type of antibiotic will have the same effect on antibiotic-resistant bacteria spread in different countries.
The scientists stress that their results warrant sustained research efforts to identify what else drives the spread of E. coli and other clinically important bacteria across a range of ecological settings. Further research is needed to fully understand the combined effect of antibiotics, travel, food production systems and other factors shaping the levels of drug resistance in a country.

Understanding more about the strains that can outcompete antibiotic-resistant E. coli can lead to new ways to help stop the spread. For example, attempts that increase the amount of non-resistant, non-harmful bacteria in an area.
Dr Anna Pöntinen, co-first author from the University of Oslo, Norway and visiting scientist at the Wellcome Sanger Institute, said: “Our large-scale study allowed us to start to answer some of the long-standing questions about what causally drives multidrug-resistant bacteria in a population. This research was only possible due to the national systematic surveillance of bacterial pathogens that occurred in the UK and Norway. Without such systems in place, scientists would be considerably more limited in terms of what can be learnt using the power of genomics.”
Professor Julian Parkhill, co-author from the University of Cambridge, said: “Our study suggests that antibiotics are modulating factors in the success of antibiotic-resistant E. coli, instead of the only cause. Our research traced the impact of several different broad-spectrum antibiotics and shows that the influence of these varies by country and area. Overall, our comprehensive genetic analysis shows that it is not always possible to predict how the use of antibiotics will impact an area without knowing the genetic makeup of the bacterial strains in that environment.”
Professor Jukka Corander, senior author from the Wellcome Sanger Institute and the University of Oslo, Norway, said: “Treatment-resistant E. coli is a major global public health issue. While it has long been accepted that the overuse of antibiotics plays a role in the rise and spread of superbugs, our study highlights that the level of drug resistance in widespread E. coli strains can vary substantially. Antibiotic use will be one selective pressure, and our study shows that it is not the only factor that impacts the success of these bacteria. Continuing to use genomics to gain a detailed understanding of the underlying drivers of bacterial success is crucial if we are to control the spread of superbugs.”
Notes: Kern WV, Rieg S. (2020) Burden of bacterial bloodstream infection — A brief update on epidemiology and significance of multidrug-resistant pathogens. Clin Microbiol Infect. DOI: 10.1016/j.cmi.2019.10.031 (https://doi.org/10.1016/j.cmi.2019.10.031) UK Health Security Agency. New data shows 148 severe antibiotic-resistant infections a day in 2021. Available at: https://www.gov.uk/government/news/new-data-shows-148-severe-antibiotic-resistant-infections-a-day-in-2021 Wang. S, Zhao. S, Zhou, et al. (2023) Antibiotic resistance spectrum of E. coli strains from different samples and age-grouped patients: a 10-year retrospective study. BMJ Open. DOI: 10.1136/bmjopen-2022-067490 (https://doi.org/10.1136/bmjopen-2022-067490)Funding:
This research was funded by the Trond Mohn Foundation, Marie Sk?odowska-Curie Actions, European Research Council, the Royal Society, and Wellcome. A full acknowledgement list can be found on the publication.

Researchers at Tohoku University have discovered a new approach for treating lymph node metastasis. Anticancer drugs are administered directly into the LNs under ultrasound guidance (Lymphatic Drug Delivery System or LDDS) to target sentinel lymph nodes (LNs) and generate antitumor effects locally, preventing distant metastasis. This approach not only improves the anticancer effect but also reduces the nasty side effects commonly associated with systemic chemotherapy.
Details of the researchers’ breakthrough were published in the journal Biomedicine & Pharmacotherapy on January 2, 2024. Professor Tetsuya Kodama from Tohoku University’s Graduate School of Engineering led the research team.
Recent research has highlighted sentinel LNs as the gateway for metastasis. They are the initial lymph nodes that receive drainage from a primary tumor and indicate that metastasis has begun or could potentially occur. Thus, there is a need for improved control of LN metastasis without surgical or radiation interventions.
Still, the occurrence of side effects can differ from individual to individual and from one treatment to another. In fact, two individuals undergoing the same treatment may encounter markedly different experiences. Most commonly, some individuals experience uncomfortable side effects that gradually diminish over time.
In a prior investigation, some of the current researchers utilized LDDS incorporating heightened osmotic pressure and viscosity of docetaxel, yielding promising outcomes in the treatment of early-stage LN metastasis during preclinical research. Based on this, they hypothesized that administering docetaxel — a widely used clinical anticancer drug — through LDDS at an osmotic pressure and viscosity of 1,960 kPa and 12 mPa∙s would result in superior antitumor effects, prolonged survival, and minimal adverse reactions.
To test this hypothesis, Kodama and his team administered the treatment to a preclinical model of a metastatic lymph node mouse model. Their findings confirmed superior therapeutic outcomes, increased complete response, improved survival, and reduced adverse complications. The double-shot administration enhanced T helper cell differentiation in the spleen and sentinel LNs, emphasizing its potential in cancer management. Histopathological assessments confirmed the efficacy, highlighting the potential of LDDS in cancer management.
The research team emphasizes the safer nature of the new method. “LDDS is a groundbreaking method to improve treatment while decreasing side effects,” says Ariunbuyan Sukhbaatar, assistant professor at the Graduate School of Dentistry and lead author of the paper. “This approach provides a safer alternative to LN removal and promises to improve cancer survival rates.”
Meanwhile, Kodama says, “LDDS offers a novel, safe method for delivering anticancer drugs to susceptible LNs, presenting a promising approach for improving cancer treatment effectiveness while minimizing side effects.”
Looking ahead, the research team aims to further investigate the LDDS with the goal of enhancing therapeutic responses against lymph node metastasis. This will be achieved through clinical trials conducted in collaboration with medical professionals, aiming to validate the effectiveness of these approaches in cancer patients.

A recent study has reported that changes in mice sperm microRNAs brought about by aging may affect the growth and development of offspring. The finding adds to the growing literature on the effects of paternal aging on offspring.
Details of the study were published in the journal Scientific Reports on December 7, 2023.
Marriages and childbearing later in life are increasingly becoming the norm. Whilst the impacts of maternal age on offspring, such as a higher risk of miscarriage and Down syndrome, are widely understood, the impacts from the paternal side are less so.
Yet this is changing. Recent epidemiological studies have demonstrated that paternal aging exerts a more substantial influence on the heightened risk of neurodevelopmental disorders such as autism spectrum disorder.
A research team led by Professor Noriko Osumi from the Department of Developmental Neuroscience at the Tohoku University Graduate School of Medicine has previously revealed that epigenetic factors, including histone modifications in spermatogenesis and DNA methylation in mice sperm, undergo changes with age. These alterations might lead to transgenerational effects.
However, the impact of paternal aging on microRNAs (miRNAs), small, non-coding RNA molecules that play a crucial role in regulating gene expression, remains under explored.
To rectify this, the same research team has conducted a comprehensive analysis of age-related variations in microRNAs in mice sperm. They compared microRNAs in sperm from mice aged 3, 12, and 20 months and identified the microRNAs that had changed in quantity.

The researchers discovered significant age-associated differences in the microRNAs. Some changes were in microRNAs responsible for regulating the nervous system and genes related to autism spectrum disorder, and these altered microRNAs included those transferred to fertilized eggs.
“Our study reveals the potential association between alteration in sperm microRNAs caused by paternal aging, underscoring the significance of investigating the impact of sperm microRNAs on offspring, an aspect that has been relatively overlooked in previous research,” states Osumi.
The anticipation is that further exploration of epigenetic factors, specifically microRNAs, will not only contribute to unraveling the pathogenic mechanisms underlying neurodevelopmental disorders but will also offer insights into promoting the health and disease prevention of successive generations.
Osumi points out that their study widens the net when it comes to exploring the link between paternal age and potential health complications in children. “While the age-related changes in oocytes are well-documented, the focus has predominantly centered on the fertility of sperm. Recognizing the myriad epigenetic transformations associated with sperm aging, as exemplified by the microRNAs examined in this study, becomes imperative.”
The findings also gain relevance in the context of Japan’s rapidly declining birthrate, which necessitates incorporating the perspective on sperm-related factors in advancing reproductive medicine.

Researchers from the Infection Biology Lab at the Department of Medicine and Life Sciences (MELIS) at Pompeu Fabra University and the HIV Unit at Hospital del Mar Research Institute have shown that intradermal vaccination with the JYNNEOS vaccine against smallpox is the best option to protect people living with HIV from contracting the monkeypox virus. This route of vaccine administration requires less material to inject each patient, extending the available vaccine doses by a factor of five. The results of this observational study also indicate that individuals with a low level of CD4 T cells, a type of white blood cell essential to properly fight new infections, need a booster dose 28 days after the first dose to compensate for their immunosuppressed status.
Monkeypox (mpox) is a zoonotic virus of the variola virus family that causes smallpox. Mpox causes an infectious disease that can spread autochthonously between humans through direct contact and respiratory routes. The most common symptoms of monkeypox infection are fever, headache, muscle pain, swollen lymph nodes, rash, respiratory and rectal symptoms, and exhaustion. Its severity depends on age and the response of the immune system to resist pathogens and parasites.
Prior to the spring of 2022, monkeypox used to appear in the form of single outbreaks in endemic areas of Central and West Africa, but at this time a global outbreak occurred that facilitated human-to-human transmission. Transmission was mainly between men who had sex with men, a population group with many HIV-infected individuals, who are particularly susceptible to monkeypox virus infection and pathogenicity.
Although there is no specific vaccine against monkeypox, the smallpox vaccine protects eight out of ten people from monkeypox infection due to the antigenic relatedness between the two viruses.
Fighting monkeypox while living with HIV
Results of the study published today in Journal of Medical Virology indicate that the activity of T cells, responsible for the response against pathogens, homeostasis and the system’s memory, in HIV-1-infected individuals, whose viral load was controlled by antiretroviral therapy, was enhanced after vaccination with the JYNNEOS smallpox vaccine. T cell responses were equivalent to those of healthy control individuals.
Among individuals living with HIV infection, there is an at-risk group that deserves special attention. It comprises so-called immunological non-responders (INR), individuals who control their viral loads after antiretroviral therapy but only partially recover their CD4 T-lymphocyte count.

“Our study shows that these INRs may need a booster dose 28 days after the first vaccination to generate an efficient T cell response and thus be protected against monkeypox,” explains Robert Güerri, the Hospital del Mar clinician who coordinated the vaccination study and is also an associate professor at UPF. Together, the new findings underscore the importance of specific studies on the immune response among people with HIV, especially those with lower CD4 white blood cells.
Vaccine administration routes modulate the immune response
Before the monkeypox outbreak in the spring of 2022, the JYNNEOS vaccine was administered subcutaneously to protect the population. But due to the increased vaccine demands, in August 2022, American and European health authorities proposed the intradermal administration route of the JYNNEOS vaccine. Via this route, the vaccine is released into the upper layer of the skin where many immune cells are located. But most importantly, this procedure extends the available vaccine doses by a factor of five, increasing vaccine availability without compromising its efficacy.
In contrast to the T-cell response of HIV-1-infected individuals who received the JYNNEOS vaccine subcutaneously, all individuals who received the vaccine intradermally generated a significant T-cell response. Therefore, intradermal vaccination was more effective in activating specific antiviral immunity.
“Our results clearly support the proposed dose-sparing vaccination route also for the protection of immunocompromised individuals who need the vaccine the most,” adds Andreas Meyerhans, an ICREA researcher and UPF full professor, who coordinated the experimental part of the study.
This study provides an early indication of how best to proceed with preventive vaccination against monkeypox in a group of individuals at high risk of infection. However, further studies should confirm and expand on the observations derived from a small number of vaccinated individuals.

Psychotherapy is an effective treatment for adults with post-traumatic stress disorder (PTSD) following exposure to multiple traumatic events. This is the conclusion arrived at by an international team of researchers led by psychologists Dr Thole Hoppen and Prof Nexhmedin Morina from the Department for Clinical Psychology and Psychotherapy at the University of Münster (Germany).
The efficacy of psychotherapeutic interventions for treating PTSD in adults has been well-documented in various studies. However, until now, it had not been established whether the efficacy of psychotherapeutic interventions varies depending on whether the disorder is caused by one single event — for example, a traffic accident — or by multiple traumatic events such as during warfare or repeated incidents of sexual or physical violence. The meta-analysis, carried out based on data from around 10,600 patients, has now been published in the journal Lancet Psychiatry.
In this study, the team of researchers — which also included Prof Richard Meiser-Stedman from the University of East Anglia (UK), Dr Ahlke Kip from the University of Münster, and Prof Marianne Skogbrott Birkeland from the Research Centre for Violence and Traumatic Stress Studies in Norway — evaluated 137 empirical articles published over the past four decades on the treatment of PTSD in adults. Nexhmedin Morina concludes: “The data show that several psychological interventions are highly effective in treating PTSD following multiple traumatic events — in fact, they are about as effective as when the PTSD follows a single trauma.” These results had, to date, only been reported for the treatment of children and adolescents with PTSD. Now, this study confirms that it also applies in the treatment of PTSD in adults. This is “very encouraging news” for both patients and therapists.
Around four per cent of the global population suffers from PTSD as a result of traumatic events. The characteristic symptoms of PTSD include distressing intrusive traumatic memories, avoidance behaviour and difficulty with emotional regulation. The new findings have implications for the clinical practice and training of psychotherapists and mental health professionals more generally.
“Our data helps remove treatment barriers for patients with a history of multiple traumatic events,” says Thole Hoppen. “In addition to patients’ fear of talking about their traumatic experiences, some psychotherapists hesitate to directly address traumatic experiences during treatment,” he adds. “However, trauma-focused cognitive behavioural therapy — a form of psychotherapy which helps process the traumatic memories — is not only very effective according to the accumulated data but more effective than non-trauma-focused interventions.”
As a result, trauma-focused cognitive behavioural therapy is the first line of treatment recommended in national and international treatment guidelines. However, adds Hoppen, future research requires longer-term data to enable a more solid estimation of the long-term efficacy of the treatment.