Explore the vast range of titles available.

Arthritis can bring with it not only pain, suffering, and physical limitations, but also a negative impact on employability, and even financial hardship. Over 46 million American adults have self-reported, doctor-diagnosed arthritis. Over a third of these individuals have limitations due to arthritis. Arthritis can bring with it not only pain, suffering, and physical limitations, but also a negative impact on employability, and even financial hardship. Over 46 million American adults have self-reported, doctor-diagnosed arthritis. As a rule, the pathology of osteoarthritis (OA) follows a progression starting with the loss of cartilage matrix that predisposes the affected joint to further injury. As OA progresses, there tends to be alterations to underlying bone as well as associated wear and tear on the cartilage with the development of bony outgrowths called osteophytes at the periphery of the affected joint. As a rule, the pathology of OA follows progression starting with loss of cartilage matrix that predisposes the affected joint to further injury.

Per- and polyfluoroalkyl substances (PFAS) are persistent and ubiquitous chemicals associated with risk of adverse birth outcomes. Results of previous studies have been inconsistent. Associations between PFAS and birth outcomes may be affected by psychosocial stress. We estimated risk of adverse birth outcomes in relation to prenatal PFAS concentrations and evaluate whether maternal stress modifies those relationships. We included 3,339 participants from 11 prospective prenatal cohorts in the Environmental influences on the Child Health Outcomes (ECHO) program to estimate the associations of five PFAS and birth outcomes. We stratified by perceived stress scale scores to examine effect modification and used Bayesian Weighted Sums to estimate mixtures of PFAS. We observed reduced birth size with increased concentrations of all PFAS. For a 1-unit higher log-normalized exposure to perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), we observed lower birthweight-for-gestational-age z-scores of [95% confidence interval (CI): , ], (95% CI: , ), (95% CI: , ), (95% CI: , 0.06), and (95% CI: , ), respectively. We observed a lower odds ratio (OR) for large-for-gestational-age: (95% CI: 0.38, 0.83), (95% CI: 0.35, 0.77). For a 1-unit increase in log-normalized concentration of summed PFAS, we observed a lower birthweight-for-gestational-age z-score [ ; 95% highest posterior density (HPD): , ] and decreased odds of large-for-gestational-age ( ; 95% HPD: 0.29, 0.82). Perfluorodecanoic acid (PFDA) explained the highest percentage (40%) of the summed effect in both models. Associations were not modified by maternal perceived stress. Our large, multi-cohort study of PFAS and adverse birth outcomes found a negative association between prenatal PFAS and birthweight-for-gestational-age, and the associations were not different in groups with high vs. low perceived stress. This study can help inform policy to reduce exposures in the environment and humans. https://doi.org/10.1289/EHP10723.

Gestational per- and polyfluoroalkyl substances (PFAS) exposure may be associated with adiposity and increased risk of obesity among children and adolescents. However, results from epidemiological studies evaluating these associations are inconsistent. We estimated the associations of pregnancy PFAS concentrations with child body mass index (BMI) -scores and risk of overweight/obesity in eight U.S. cohorts. We used data from 1,391 mother-child pairs who enrolled in eight Environmental influences on Child Health Outcomes (ECHO) cohorts (enrolled: 1999-2019). We quantified concentrations of seven PFAS in maternal plasma or serum in pregnancy. We measured child weight and height between the ages of 2 and 5 y and calculated age- and sex-specific BMI -scores; 19.6% children had more than one BMI measurement. We estimated covariate-adjusted associations of individual PFAS and their mixture with child BMI -scores and risk of overweight/obesity using linear mixed models, modified Poisson regression models, and Bayesian approaches for mixtures. We explored whether child sex modified these associations. We observed a pattern of subtle positive associations of PFAS concentrations in pregnancy with BMI -scores and risk of overweight/obesity. For instance, each doubling in perfluorohexane sulfonic acid concentrations was associated with higher BMI -scores ( ; 95% CI: 0.01, 0.12). Each doubling in perfluroundecanoic acid [ ; 95% CI: 1.04, 1.16] and -methyl perfluorooctane sulfonamido acetic acid ( ; 95% CI: 1.00, 1.12) was associated with increased risk of overweight/obesity, with some evidence of a monotonic dose-response relation. We observed weaker and more imprecise associations of the PFAS mixture with BMI or risk of overweight/obesity. Associations did not differ by child sex. In eight U.S.-based prospective cohorts, gestational exposure to higher levels of PFAS were associated with slightly higher childhood BMI -score and risk of overweight or obesity. Future studies should examine associations of gestational exposure to PFAS with adiposity and related cardiometabolic consequences in older children. https://doi.org/10.1289/EHP11545.

CRISPR-associated (Cas) transposases (CAST) are RNA-guided systems capable of programmable integration of large segments of DNA without creating double-strand breaks. Engineered Cascade CAST function in human cells but are challenging to deploy due to the complexity of the targeting components. Unlike Cascade, which require three Cas proteins, type V-K CAST require a single Cas12k effector for targeting. Here, we show that compact type V-K CAST from uncultivated microbes are repurposable for programmable DNA integration into the genome of human cells. Engineering for nuclear localization and function enables integration of a therapeutically relevant transgene at a safe-harbor site in multiple human cell types. Notably, off-targets are rare events reproducibly found in specific genomic regions. These CAST advancements are expected to accelerate applications of genome editing to therapeutic development, biotechnology, and synthetic biology. RNA-guided CRISPR-associated transposases (CAST) are natural systems with broad potential in biotechnology. Here, the authors report compact type V-K CAST discovered from genome-resolved metagenomics and demonstrate targeted integration of a large transgene to a safe-harbor site in the human genome.

BackgroundSchizophrenia and bipolar disorder are complex mental illnesses that are associated with cognitive deficits. There is considerable cognitive heterogeneity that exists within both disorders. Studies that cluster schizophrenia and bipolar patients into subgroups based on their cognitive profile increasingly demonstrate that, relative to healthy controls, there is a severely compromised subgroup and a relatively intact subgroup. There is emerging evidence that telomere shortening, a marker of cellular senescence, may be associated with cognitive impairments. The aim of this study was to explore the relationship between cognitive subgroups in bipolar-schizophrenia spectrum disorders and telomere length against a healthy control sample.MethodsParticipants included a transdiagnostic group diagnosed with bipolar, schizophrenia or schizoaffective disorder (n = 73) and healthy controls (n = 113). Cognitive clusters within the transdiagnostic patient group, were determined using K-means cluster analysis based on current cognitive functioning (MATRICS Consensus Cognitive Battery scores). Telomere length was determined using quantitative PCRs genomic DNA extracted from whole blood. Emergent clusters were then compared to the healthy control group on telomere length.ResultsTwo clusters emerged within the patient group that were deemed to reflect a relatively intact cognitive group and a cognitively impaired subgroup. Telomere length was significantly shorter in the severely impaired cognitive subgroup compared to the healthy control group.ConclusionsThis study replicates previous findings of transdiagnostic cognitive subgroups and associates shorter telomere length with the severely impaired cognitive subgroup. These findings support emerging literature associating cognitive impairments in psychiatric disorders to accelerated cellular aging as indexed by telomere length.

Planetary nebulae form toward the end of the lives of sunlike stars. They appear after the star has shed its outer layers, and radiation from what is left of it ionizes the surrounding medium. Using the Very Large Telescope in Chile, Boffin et al. (p. 773 ) obtained spectra of the star at the center of Fleming 1, a point-symmetric planetary nebula with rotating bipolar jets. It has long been assumed that jets like these arose from an interacting binary system. Indeed, the data reveal that the central star in Fleming 1 has a companion in a very close orbit. Spectra of a planetary nebula’s central star reveal a companion star responsible for launching the system’s rotating jets. Stars are generally spherical, yet their gaseous envelopes often appear nonspherical when ejected near the end of their lives. This quirk is most notable during the planetary nebula phase, when these envelopes become ionized. Interactions among stars in a binary system are suspected to cause the asymmetry. In particular, a precessing accretion disk around a companion is believed to launch point-symmetric jets, as seen in the prototype Fleming 1. Our finding of a post–common-envelope binary nucleus in Fleming 1 confirms that this scenario is highly favorable. Similar binary interactions are therefore likely to explain these kinds of outflows in a large variety of systems.