To assess short term mortality risks and excess mortality associated with exposure to ozone in several cities worldwide.
Funding for human papillomavirus (HPV) vaccination in Japan began in 2010 for girls aged 12-16 years, with three-dose coverage initially reaching more than 70%. On June 14, 2013, 2 months after formal inclusion in Japan’s national immunisation programme, proactive recommendations for the HPV vaccine were suspended following reports of adverse events since found to be unrelated to vaccination, but which were extensively covered in the media. Vaccine coverage subsequently dropped to less than 1% and has remained this low to date. We aimed to quantify the impact of this vaccine hesitancy crisis, and the potential health gains if coverage can be restored.
Human gut microbiomes are known to change with age, yet the relative value of human microbiomes across the body as predictors of age, and prediction robustness across populations is unknown. In this study, we tested the ability of the oral, gut, and skin (hand and forehead) microbiomes to predict age in adults using random forest regression on data combined from multiple publicly available studies, evaluating the models in each cohort individually. Intriguingly, the skin microbiome provides the best prediction of age (mean ± standard deviation, 3.8 ± 0.45 years, versus 4.5 ± 0.14 years for the oral microbiome and 11.5 ± 0.12 years for the gut microbiome). This also agrees with forensic studies showing that the skin microbiome predicts postmortem interval better than microbiomes from other body sites. Age prediction models constructed from the hand microbiome generalized to the forehead and vice versa, across cohorts, and results from the gut microbiome generalized across multiple cohorts (United States, United Kingdom, and China). Interestingly, taxa enriched in young individuals (18 to 30 years) tend to be more abundant and more prevalent than taxa enriched in elderly individuals (>60 yrs), suggesting a model in which physiological aging occurs concomitantly with the loss of key taxa over a lifetime, enabling potential microbiome-targeted therapeutic strategies to prevent aging.IMPORTANCE Considerable evidence suggests that the gut microbiome changes with age or even accelerates aging in adults. Whether the age-related changes in the gut microbiome are more or less prominent than those for other body sites and whether predictions can be made about a person’s age from a microbiome sample remain unknown. We therefore combined several large studies from different countries to determine which body site’s microbiome could most accurately predict age. We found that the skin was the best, on average yielding predictions within 4 years of chronological age. This study sets the stage for future research on the role of the microbiome in accelerating or decelerating the aging process and in the susceptibility for age-related diseases.
Infant cognitive development is influenced by maternal factors that range from obesity to early feeding and breast milk composition. Animal studies suggest a role for human milk oligosaccharide (HMO), 2'-fucosyllactose (2'FL), on learning and memory, yet no human studies have examined its impact on infant cognitive development relative to other HMOs and maternal factors.
There is growing recognition that some autistic people engage in ‘compensation’, showing few behavioural symptoms (e.g. neurotypical social skills), despite continuing to experience autism-related cognitive difficulties (e.g. difficulties in social cognition). One way this might be achieved is by individuals consciously employing ‘compensatory strategies’ during everyday social interaction. However, very little is currently known about the broad range of these strategies, their mechanisms and consequences for clinical presentation and diagnosis.
Psilocybin is a classic psychedelic compound that may have efficacy for the treatment of mood and substance use disorders. Acute psilocybin effects include reduced negative mood, increased positive mood, and reduced amygdala response to negative affective stimuli. However, no study has investigated the long-term, enduring impact of psilocybin on negative affect and associated brain function. Twelve healthy volunteers (7F/5M) completed an open-label pilot study including assessments 1-day before, 1-week after, and 1-month after receiving a 25 mg/70 kg dose of psilocybin to test the hypothesis that psilocybin administration leads to enduring changes in affect and neural correlates of affect. One-week post-psilocybin, negative affect and amygdala response to facial affect stimuli were reduced, whereas positive affect and dorsal lateral prefrontal and medial orbitofrontal cortex responses to emotionally-conflicting stimuli were increased. One-month post-psilocybin, negative affective and amygdala response to facial affect stimuli returned to baseline levels while positive affect remained elevated, and trait anxiety was reduced. Finally, the number of significant resting-state functional connections across the brain increased from baseline to 1-week and 1-month post-psilocybin. These preliminary findings suggest that psilocybin may increase emotional and brain plasticity, and the reported findings support the hypothesis that negative affect may be a therapeutic target for psilocybin.
Infections have numerous effects on the brain. However, possible roles of the brain in protecting against infection, and the developmental origin and role of brain signaling in immune response, are largely unknown. We exploited a unique Xenopus embryonic model to reveal control of innate immune response to pathogenic E. coli by the developing brain. Using survival assays, morphological analysis of innate immune cells and apoptosis, and RNA-seq, we analyzed combinations of infection, brain removal, and tail-regenerative response. Without a brain, survival of embryos injected with bacteria decreased significantly. The protective effect of the developing brain was mediated by decrease of the infection-induced damage and of apoptosis, and increase of macrophage migration, as well as suppression of the transcriptional consequences of the infection, all of which decrease susceptibility to pathogen. Functional and pharmacological assays implicated dopamine signaling in the bacteria-brain-immune crosstalk. Our data establish a model that reveals the very early brain to be a central player in innate immunity, identify the developmental origins of brain-immune interactions, and suggest several targets for immune therapies.
Successful reproduction is a fundamental physiological process that relies on the integration of sensory cues of attraction with appropriate emotions and behaviors and the reproductive axis. However, the factors responsible for this integration remain largely unexplored. Using functional neuroimaging, hormonal, and psychometric analyses, we demonstrate that the reproductive hormone kisspeptin enhances brain activity in response to olfactory and visual cues of attraction in men. Furthermore, the brain regions enhanced by kisspeptin correspond to areas within the olfactory and limbic systems that govern sexual behavior and perception of beauty as well as overlap with its endogenous expression pattern. Of key functional and behavioral significance, we observed that kisspeptin was most effective in men with lower sexual quality-of-life scores. As such, our results reveal a previously undescribed attraction pathway in humans activated by kisspeptin and identify kisspeptin signaling as a new therapeutic target for related reproductive and psychosexual disorders.
Maximizing the flow of students through the science, technology, engineering, and math (STEM) pipeline is important to promoting human capital development and reducing economic inequality. A critical juncture in the STEM pipeline is the highly cumulative sequence of secondary school math courses. Students from disadvantaged schools are less likely to complete advanced math courses. Here, we conduct an analysis of how the math pipeline differs across schools using student polygenic scores, which are DNA-based indicators of propensity to succeed in education. We integrated genetic and official school transcript data from over 3000 European-ancestry students from U.S. high schools. We used polygenic scores as a molecular tracer to understand how the flow of students through the high school math pipeline differs in socioeconomically advantaged versus disadvantaged schools. Students with higher education polygenic scores were tracked to more advanced math already at the beginning of high school and persisted in math for more years. Analyses using genetics as a molecular tracer revealed that the dynamics of the math pipeline differed by school advantage. Compared to disadvantaged schools, advantaged schools buffered students with low polygenic scores from dropping out of math. Across all schools, even students with exceptional polygenic scores (top 2%) were unlikely to take the most advanced math classes, suggesting substantial room for improvement in the development of potential STEM talent. These results link new molecular genetic discoveries to a common target of educational-policy reforms.
Susceptibility to diseases is common to humans and dinosaurs. Since much of the biological history of every living creature is shaped by its diseases, recognizing them in fossilized bone can furnish us with important information on dinosaurs' physiology and anatomy, as well as on their daily activities and surrounding environment. In the present study, we examined the vertebrae of two humans from skeletal collections with Langerhans Cell Histiocytosis (LCH), a benign osteolytic tumor-like disorder involving mainly the skeleton; they were diagnosed in life, along with two hadrosaur vertebrae with an apparent lesion. Macroscopic and microscopic analyses of the hadrosaur vertebrae were compared to human LCH and to other pathologies observed via an extensive pathological survey of a human skeletal collection, as well as a three-dimensional reconstruction of the lesion and its associated blood vessels from a µCT scan. The hadrosaur pathology findings were indistinguishable from those of humans with LCH, supporting that diagnosis. This report suggests that hadrosaurids had suffered from larger variety of pathologies than previously reported. Furthermore, it seems that LCH may be independent of phylogeny.