The National Institute for Public Health and the Environment (Dutch: Rijksinstituut voor Volksgezondheid en Milieu or simply RIVM) is a Dutch research institute that is an independent agency of the Ministry of Health, Welfare and Sport.RIVM performs tasks to promote public health and a safe living environment by conducting research and collecting knowledge worldwide. The results are used to support the Government of the Netherlands in formulating its policy. RIVM's primary tasks are:RIVM is located in Bilthoven, Utrecht and employs over 1,500 people, many of whom work in multidisciplinary fields.
Bacteria of the Spiroplasma ixodetis clade are well characterized as reproductive parasites and defensive endosymbionts of arthropods. Nevertheless, clinical evidence indicates that they can also infect humans, causing neonatal ocular disease and acute febrile illness in adults. Using metagenomic assembly and phylogenomic analyses of Spiroplasma ixodetis-related human infections (SiRHIs), combined with a systematic meta-analysis of public datasets, we identified 25 human cases across ten European countries. Despite the frequent detection of multiple S. ixodetis strains in ticks, our data provide no evidence implicating tick-associated strains in human infections. Instead, SiRHI constitute a distinct monophyletic lineage within the S. ixodetis clade, consistent with a shared evolutionary origin with arthropod-associated relatives. Notably, SiRHI genomes harbor horizontally acquired chaperone genes absent from most arthropod-associated Spiro-plasma, while retaining conserved effector genes typical of endosymbionts, suggesting the preservation of ancestral symbiotic traits alongside newly acquired molecular adaptations.
BACKGROUND:Respondent-driven sampling (RDS) is a social network sampling technique used to study hidden behaviours. We used web-based RDS (webRDS) to estimate the prevalence of self-managed abortion (SMA) outside the formal healthcare system in Argentina where abortion was legalised in 2020, but access remains uneven. METHODS:A cross-sectional web survey (February-May 2024) among individuals aged 16-49 years, ever pregnant, and residing in Argentina. Our primary outcome was the proportion of SMA occurring outside the formal healthcare system. Estimates were generated using the RDS II estimator. RESULTS:Seven recruitment chains generated 2437 participants (mean of 19.8 recruitment waves, the longest being 51). We filtered for suspected repeat and ineligible participation and generated RDS estimates for the remaining 1340 participants. The estimated personal network size was 4.9; participants knew an average of 2.7 peers with abortion experience. An estimated 17.1% reported ≥1 abortion, ever in life. Among these, an estimated 20.7% (95% CI 14.2 to 28.0) reported an SMA outside the formal healthcare system; 65.3% before and 24.7% after the legal reform. An estimated 42.2% completed the SMA alone. Reported advantages included autonomy in timing and setting, and support person choice. Disadvantages included concerns about pill quality and uncertainties around the process. CONCLUSIONS:A substantial proportion of women in Argentina with abortion experience have had an SMA outside the formal healthcare system, including post-legalisation. Our findings highlight the need to better address the preferences and needs of those facing unintended pregnancy and the potential of webRDS to study SMA.
Harmonized phenotyping and diverse population-specific studies are crucial for advancing gene discovery in psychiatric genetics. We conducted a genome-wide association (GWAS) mega-analysis of DSM-defined lifetime major depressive disorder (MDD) in 64 941 participants (25.7% cases) from the Dutch BIObanks Netherlands Internet Collaboration (BIONIC) consortium. Liability-scale SNP-based heritability was 12.0% (SE = 1.4%) as estimated by LDSC (assuming a lifetime prevalence of 15%) and 26.6% (SE = 1.1%) when estimated by LDAK-REML on individual-level genotype data, indicating substantial common-variant signal in this clinically harmonized sample. The genetic correlation with the latest major depression GWAS from the Psychiatric Genomics Consortium (PGC-MD) was high (rG = 0.89, SE = 0.048). Polygenic scores (PGSs) based on BIONIC predicted depression in UK Biobank, and PGSs derived from PGC-MD predicted MDD in BIONIC, supporting transferability of depression polygenic signal across cohorts and phenotype definitions. Within-family PGS analyses in twins suggested that the observed prediction was not primarily driven by detectable family-level confounding, and twin concordance for MDD increased with polygenic burden. We identified one genome-wide significant locus, indexed by rs3818852 in PALMD, but this finding currently lacks independent replication and should be interpreted cautiously. Finally, genetic correlation and latent causal variable analyses identified multiple traits showing shared or directionally consistent genetic associations with MDD. Together, these findings underscore the value of clinically harmonized phenotyping in regional biobank collaborations for studying the genetic architecture of MDD.
BACKGROUND:Having obesity is a risk factor for cognitive decline and dementia. It remains unclear whether timing of obesity during someone's lifespan affects this association. AIM:To study the association of body mass index (BMI), waist circumference (WC), and having (abdominal) overweight and obesity with cognitive function and decline, and whether these associations were modified by age. METHODS:3873 participants (aged 45-70 at baseline, 52% women) from the Doetinchem Cohort Study were included, with up to six repeated measures. Participants were classified as having (abdominal) obesity if they had a BMI ≥30 kg/m² or WC ≥102 cm (men) or ≥88 cm (women). Domain scores for global cognition, memory, flexibility, and processing speed were calculated by standardizing individual test scores at baseline. Associations of time-dependent BMI, WC, and (abdominal) overweight and obesity with cognitive function and decline were studied using linear mixed models. Models were sex-stratified and adjusted for socio-demographic, lifestyle, and mental health factors. Modification by age (≤ or >55 years at baseline) was evaluated using interaction terms. RESULTS:Higher BMI and WC were associated with worse level of cognition (all domains). For both sexes, the smallest difference was for global cognition (BMI) and processing speed (WC), the largest for flexibility (BMI) and memory (WC). Furthermore, having (abdominal) obesity, compared to a healthy BMI/WC, was consistently associated with worse memory function in both sexes. Effect sizes were generally larger for categorical WC compared to categorical BMI. In men, abdominal obesity was associated with accelerated decline in processing speed (all ages), and with accelerated decline in global cognition and flexibility ( > 55 years). CONCLUSIONS:In both sexes, higher BMI and WC were consistently associated with worse cognition. WC-based overweight and obesity showed larger effect sizes with cognition than BMI-based overweight and obesity. Only in men, associations with cognitive decline and effect modification by age were observed.
The human toxicological risk assessment of per- and polyfluoroalkyl substances (PFAS) is challenging, due to their sheer number and structural diversity, but also the paucity of the toxicity data required to characterize them. The development of Next Generation Physiologically Based Kinetic (NG-PBK) models may assist in overcoming this challenge. The mechanistic nature of NG-PBK models allows for their extrapolation from data-rich PFAS, such as perfluorooctanoic acid (PFOA), to data-poor ones, facilitating their application in Next Generation Risk Assessment (NGRA). The present study proposes a NG-PBK model for PFOA in humans, parametrized exclusively using in vitro-, and in silico-derived data. The model describes the toxicokinetic processes of 1) partitioning to plasma and tissue proteins, 2) partitioning to cell membrane lipids, 3a) transporter-mediated entero-hepatic circulation and 3b) renal elimination and reabsorption, and 4) elimination via menstruation. Global sensitivity analysis indicated that the model was most sensitive to the fraction unbound in plasma, active-transport parameters, and tissue-plasma partition coefficients. The model was equivalent to already available validated human PFOA-PBK models, while compared to those, it is not calibrated to observed animal, nor human data, illustrating its strength in being mechanistic. The serum concentrations and half-lives predicted by the NG-PBK model were within the ranges of those reported in human volunteer and biomonitoring (HBM) studies, demonstrating the model's capacity to accurately predict PFOA toxicokinetics on exposure estimates. Extrapolation of the NG-PBK model to other PFAS, in conjunction with its integration with HBM data, will facilitate the NGRA of PFAS. This is particularly relevant given the paucity of in vivo data for most PFAS, ensuring compliance with the 3R principles.
