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Metabolic dysfunction-associated steatotic liver disease (MASLD) is primarily driven by a Western-style diet and exacerbated with aging, yet underlying mechanisms remain unclear. Given the essential role of thyroid hormone (TH) in MASLD progression, we hypothesized that impaired intrahepatic TH action during aging promotes MASLD progression and severity of MASH with fibrosis. We evaluated hepatic TH metabolism in young (18-24 weeks) and old (108-120 weeks) C57BL/6J mice fed either a normal chow diet (NCD) or a Western diet with fructose (WDF) for 8 weeks. Liver histology, metabolic parameters, inflammatory and fibrotic markers, intrahepatic thyroxine (T4) and triiodothyronine (T3) concentrations, and activities of deiodinase enzymes (Dio1 and Dio3) were measured. Additionally, an in vitro hepatocyte senescence model using AML12 cells was employed to assess age-related alterations in deiodinase expression and the therapeutic efficacy of resmetirom (an FDA-approved thyromimetic). Aging and WDF synergistically exacerbated hepatic inflammation and fibrosis, accompanied by significant reductions in intrahepatic T4 and T3. Aging markedly decreased Dio1 activity, which converts T4 to active T3, whereas WDF partially restored Dio1 in old mice. Conversely, Dio3 activity, responsible for TH inactivation, increased with age but exhibited age-dependent differential responses to WDF, findings mirrored in senescent hepatocytes. Notably, resmetirom significantly reduced senescence markers, inhibited senescence-associated secretory phenotype (SASP) genes, inflammasome activation, endoplasmic reticulum (ER) stress, and activated autophagy. Collectively, our findings demonstrate that aging and stress by a Western-style diet synergistically impair hepatic TH signaling, accelerating MASLD progression. Furthermore, resmetirom improved hepatic senescence, highlighting its potential therapeutic repurposing for aging-associated hepatic pathologies, including MASLD.

The “risk compensation hypothesis” holds that unvaccinated individuals may be more motivated to protect themselves using other COVID-19 mitigation behaviors—e.g., masking, distancing and hand hygiene—given that they are their only line of defense. The current investigation provides an empirical test of the risk compensation hypothesis in the COVID-19 context using prospective data from the Canadian COVID-19 Experiences Survey (CCES). The survey comprised 1,958 unvaccinated and fully vaccinated individuals drawn from a representative sample, using quota sampling to ensure substantial representation of unvaccinated individuals. Two waves of data were collected 6 months apart. Findings revealed that vaccinated individuals performed COVID-19 mitigation behaviors significantly more frequently than their unvaccinated counterparts, and they also showed lower rates of attenuation as the pandemic continued. In summary, our findings do not support the risk compensation hypothesis; instead they support the notion that people adopt vaccination and other protective behaviors in parallel.

[Display omitted] •A method using targeted proteomics based on HRAM Orbitrap MS for direct detection of TEM and SHV was developed.•Five specific peptides with high subtype coverage were initially identified as peptide markers for TEM and SHV.•A large proportion of silent or low expression of TEM and SHV were observed in strains carrying the blaTEM or blaSHV.•The low/no-expression of TEM and SHV is associated with gene location, promoter strength, and transcriptional regulation.

Methane emissions from plants in wetlands are mainly due to internal transport, from the anoxic soil layers where methane is produced, to the atmosphere. This pathway has not yet been clearly demonstrated for upland forest vegetation, where methane can be produced in deep soil layers. We developed a new method to trace methane transfer from the deep soil. We conducted a ¹³CH₄ pulse labelling at 40-cm soil depth and then monitored ¹³CH₄ in the upper horizons, at the soil surface (with or without understorey vegetation) and emitted by tree stems until the total disappearance of the labelled gas. Most of the injected ¹³CH₄ was oxidized in the soil despite high soil water content. The understorey vegetation did not contribute to ¹³CH₄ emission by the soil. We prove that tree stems can emit methane produced in an upland forest soil, even when the said soil is a net methane sink. We conclude that pulse labelling with ¹³CH₄ and tracing by laser-based spectrometry is a promising tool approach to study the transport of methane from production to emission.

Over recent decades, patient and public involvement (PPI) has become a more established element of health research policy, although its implementation is often criticised for tokenism and for underrepresenting marginalized groups. In fields such as complex chronic illness (CCI), where formal research activity has historically been limited, conventional PPI frameworks have had little scope for meaningful application. Within this context, a new wave of patient-led initiatives has emerged that moves beyond participation in existing systems toward the creation of independent infrastructures for knowledge generation, extending the principle of “nothing about us, without us.” This commentary examines Visible, a patient-founded health technology platform that combines daily energy-management tools with research infrastructure for CCIs. This infrastructure enables in-house data analyses and external collaborations, including app-based data studies, investigator-led research, and integration within clinical trials. We explore the advantages of this dual-purpose model, including greater inclusivity, sustained engagement, and richer longitudinal data. We also describe how embedding research functions within tools that patients find directly useful allows evidence generation and patient support to be mutually reinforcing.

Pour améliorer l'accès aux soins des usagers de substances psychoactives dans la ville de Bobo-Dioulasso, le Centre de Soins, “Colibri Sud” a été créé. Cette étude avait pour objectif de décrire le profil des usagers de substances psychoactives qui ont fréquenté le Centre Médical “Colibri Sud” après 13 mois d'activités. Il s'est agi d'une étude transversale descriptive sur des données collectées du 1er mars 2022 au 31 mars 2023. Les variables collectées étaient le sexe, l'âge, la profession et le type de substance consommée. L'analyse des données a été faite avec le logiciel STATA 16. Un test de Fisher exact de 5% a été considéré comme significatif. Au total, 116 patients ont été inclus dans notre étude. Les substances les plus consommées étaient le cannabis (75,86%), les benzodiazépines (25%), les opiacées (11,2%), les barbituriques 6,9%), cocaïne (3,44%). Les polyconsommateurs représentaient 15,50%. Les patients de moins de 30 ans étaient les plus représentés (67,24%) ainsi que les travailleurs du secteur informel (40,52%) et les élèves/étudiants (31,03%). Le centre est fréquenté par une population masculine à majorité jeune, le cannabis reste la substance la plus consommée. Cependant les benzodiazépines, les opiacées et la polyconsommation jadis rare est maintenant non négligeable. Au regard des profils retrouvés, l'accessibilité aux tests chromatographiques de détection et de quantification de ces substances psychoactives est plus que nécessaire pour une meilleure prise en charge. Aussi les actions entreprises doivent être surtout en faveur des élèves et étudiants. The “Colibri Sud” care centre was set up to improve access to care for psychoactive substance users in the city of Bobo-Dioulasso. The purpose of this study was to describe the profile of psychoactive substance users who attended the “Colibri Sud” Medical Centre after 13 months of activity. We conducted a descriptive cross-sectional study based on data collected from March 1st, 2022, to March 31st, 2023. The variables collected included sex, age, occupation, and the type of substance used. Data analysis was performed using STATA 16 software. A Fisher's exact test with a 5% significance level was considered significant. A total of 116 patients were included in the study. The most commonly used substances were cannabis (75.86%), benzodiazepines (25%), opiates (11.2%), barbiturates (6.9%), and cocaine (3.44%). Poly-drug users accounted for 15.50% of the sample. Patients under 30 years of age were the most represented (67.24%), as well as workers in the informal sector (40.52%) and students (31.03%). The centre is frequented predominantly by a young male population and cannabis remains the most commonly used substance. However, the use of benzodiazepines, opiates, and poly-drug use, which was previously rare, is now significant. Given the profiles observed, access to chromatographic tests for detecting and quantifying these psychoactive substances is crucial for better management. Additionally, actions undertaken should particularly target students.

Rabies presents with a high fatality rate, which imposes a significant global public health challenge, and therefore the use of post-exposure prophylaxis (PEP) is crucial for prevention. Monoclonal antibodies (mAbs) have emerged as a promising substitute for rabies immunoglobulins (RIGs) due to their high efficacy and standardized manufacturing process. A prospective, open-label, post-marketing surveillance study (PMS) was conducted at Byramjee Jeejeebhoy Medical College (BJMC), Pune. The study included patients aged more than 2 years who had recently sustained Category III-suspected rabid animal bite exposures. These patients were administered TwinRabTM at a dosage of 40 IU/kg in and around the wound as intralesional transfer, along with the anti-rabies vaccine (ARV). Adverse events (AEs) grading was performed with reference to the Food and Drug Administration (FDA) toxicity grading. In this study, 215 subjects received the TwinRabTM mAb with a 100% completion rate. Out of 215 patients, three (1.3%) patients in the range of 18 to 65 years of age showed solicited local AEs, which were resolved after the appropriate treatment intervention, but causality assessment was non-assessable. The overall tolerability assessment showed positive ratings from doctors (91.63%) and patients (67.91%) for the mAb cocktail. The PMS demonstrated the safety of TwinRabTM in patients who experienced Category III-suspected rabid animal bites, thereby supporting its potential as an alternative option for post-exposure prophylaxis in the management of animal bites for the prevention of rabies