BACKGROUND: Exposure to benzophenone-1 (BP-1) and benzophenone-3 (BP-3), widely used as UV filters in personal care products, has been associated with adverse health effects. However, epidemiological evidence is limited and inconclusive, particularly in vulnerable populations such as teenagers. OBJECTIVE: To examine the relation between BP-1 and BP-3 concentrations and obesity, cardiometabolic biomarkers, and asthma/allergy outcomes in European teenagers, including possible sex-specific associations. METHODS: A multi-country cross-sectional study was conducted using pooled data from six aligned studies from the Human Biomonitoring for Europe Initiative (HBM4EU). Sociodemographic data, cardiometabolic biomarkers, and asthma/allergy outcomes were collected through questionnaires. Anthropometric data and BMI z-scores were calculated (n = 1339). Plasma/serum cardiometabolic biomarkers and asthma/allergy outcomes were available for a subsample (n = 173-594). Urinary BP-1 and BP-3 concentrations were adjusted for creatinine dilution using the traditional standardization (trad.) and the covariate-adjusted creatinine standardization (CAS) method. Generalized additive models, linear, logistic, and multinomial mixed models were applied, and sex-interaction terms were tested. RESULTS: Each natural log-unit increase in urinary BP-3 (CAS) concentrations was associated with higher odds of obesity in the whole population (OR: 1.20; 95%CI: 1.04-1.38). Sex-specific associations were also found with BP-1 (CAS) and BP-3 (CAS) concentrations, which were associated with higher odds of obesity in male teenagers (OR: 1.25; 95% CI: 1.01-1.55; OR: 1.34; 95%CI: 1.09-1.65, respectively). Linear mixed models showed consistent findings toward higher BMI z-scores. A negative association was found between BP-1 (CAS) concentration and serum adiponectin levels in females (% change per loge-unit increase: -3.73, 95%CI: -7.32, -0.10). BP-3 (CAS) concentrations were also associated with higher odds of non-food allergies in males (OR: 1.27; 95%CI: 1.00-1.63). Traditional creatinine adjustment showed similar or slightly attenuated estimates compared to the CAS method. CONCLUSIONS: BP-1 and BP-3 exposure was cross-sectionally associated with higher odds of obesity in European male teenagers, highlighting the need to update regulations and keep exposure levels as low as practically achievable. Longitudinal studies are needed to confirm these findings.

• MeSH
• Hypersensitivity * epidemiology   MeSH
• Benzophenones * toxicity   urine   adverse effects   MeSH
• Biomarkers blood   MeSH
• Biological Monitoring MeSH
• Asthma * epidemiology   chemically induced   MeSH
• Humans MeSH
• Adolescent MeSH
• Obesity * epidemiology   chemically induced   MeSH
• Sunscreening Agents * adverse effects   MeSH
• Cross-Sectional Studies MeSH
• Environmental Exposure * MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Europe MeSH

Estimating structural connectivity from diffusion-weighted magnetic resonance imaging is a challenging task, partly due to the presence of false-positive connections and the misestimation of connection weights. Building on previous efforts, the MICCAI-CDMRI Diffusion-Simulated Connectivity (DiSCo) challenge was carried out to evaluate state-of-the-art connectivity methods using novel large-scale numerical phantoms. The diffusion signal for the phantoms was obtained from Monte Carlo simulations. The results of the challenge suggest that methods selected by the 14 teams participating in the challenge can provide high correlations between estimated and ground-truth connectivity weights, in complex numerical environments. Additionally, the methods used by the participating teams were able to accurately identify the binary connectivity of the numerical dataset. However, specific false positive and false negative connections were consistently estimated across all methods. Although the challenge dataset doesn't capture the complexity of a real brain, it provided unique data with known macrostructure and microstructure ground-truth properties to facilitate the development of connectivity estimation methods.

• MeSH
• Diffusion Magnetic Resonance Imaging * methods   MeSH
• Phantoms, Imaging MeSH
• Humans MeSH
• Monte Carlo Method MeSH
• Brain diagnostic imaging   MeSH
• Image Processing, Computer-Assisted * methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.

• MeSH
• Alzheimer Disease * genetics   MeSH
• Histocompatibility Antigens MeSH
• HLA Antigens MeSH
• HLA-DRB1 Chains * genetics   MeSH
• Humans MeSH
• Parkinson Disease * genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

• MeSH
• Autophagy * physiology   MeSH
• Autophagosomes MeSH
• Biomarkers MeSH
• Biological Assay standards   MeSH
• Humans MeSH
• Lysosomes MeSH
• Autophagy-Related Proteins metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Guideline MeSH

• MeSH
• Autophagy * physiology   MeSH
• Biological Assay methods   standards   MeSH
• Humans MeSH
• Computer Simulation MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, N.I.H., Extramural MeSH
• Guideline MeSH