Mental health challenges among adolescents living with HIV

Introduction: Mental health is a critical and neglected global health challenge for adolescents infected with HIV. The prevalence of mental and behavioural health issues among HIV-infected adolescents may not be well understood or addressed as the world scales up HIV prevention and treatment for adolescents. The objective of this narrative review is to assess the current literature related to mental health challenges faced by adolescents living with HIV, including access to mental health services, the role of mental health challenges during transition from paediatric to adult care services and responsibilities, and the impact of mental health interventions., Methods: For each of the topics included in this review, individual searches were run using Medline and PubMed, accompanied by scans of bibliographies of relevant articles. The topics on which searches were conducted for HIV-infected adolescents include depression and anxiety, transition from paediatric to adult HIV care and its impact on adherence and mental health, HIV-related, mental health services and interventions, and the measurement of mental health problems. Articles were included if the focus was consistent with one of the identified topics, involved HIV-infected adolescents, and was published in English., Results and Discussion: Mental and behavioural health challenges are prevalent in HIV-infected adolescents, including in resource-limited settings where most of them live, and they impact all aspects of HIV prevention and treatment. Too little has been done to measure the impact of mental health challenges for adolescents living with HIV, to evaluate interventions to best sustain or improve the mental health of this population, or to create healthcare systems with personnel or resources to promote mental health., Conclusions: Mental health issues should be addressed proactively during adolescence for all HIV-infected youth. In addition, care systems need to pay greater attention to how mental health support is integrated into the care management for HIV, particularly throughout lifespan changes from childhood to adolescence to adulthood. The lack of research and support for mental health needs in resource-limited settings presents an enormous burden for which cost-effective solutions are urgently needed

REM Sleep Behavior and Motor Findings in Parkinson’s Disease: A Cross-sectional Analysis

Background: Parkinson's disease (PD) represents a major public health challenge that will only grow in our aging population. Understanding the connection between PD and associated prodromal conditions, such as rapid eye movement sleep behavioral disorder (RBD), is critical to identifying prevention strategies. However, the relationship between RBD and severity of motor findings in early PD is unknown. This study aims to examine this relationship. Methods: The study population consisted of 418 PD patients who completed the Movement Disorders Society‐United Parkinson's Disease Rating Scale (MDS‐UPDRS) and rapid eye movement sleep (REM) disorder questionnaires at the baseline visit of the Michael J. Fox's Parkinson's Progression Markers Initiative (PPMI). Cross‐sectional analysis was carried out to assess the association between REM Sleep Behavior Screening Questionnaire score and MDS UPDRS‐3 (motor) score categories. Correlation with a higher score category was described as “worse motor findings”. A score of 5 on the REM disorder questionnaire was defined as predictive of RBD. Results: Out of the 418 PD patients, 113 (27.0%) had RBD. With univariate logistic regression analysis, individuals with scores predictive of RBD were 1.66 times more likely to have worse motor findings (p = 0.028). Even with age, gender, and Geriatric Depression Scale scores taken into account, individuals with scores predictive of RBD were 1.69 times more likely to have worse motor findings (p = 0.025). Discussion: PD patients with RBD symptoms had worse motor findings than those unlikely to have RBD. This association provides further evidence for the relationship between RBD and PD

Local adaptation and archaic introgression shape global diversity at human structural variant loci.

Large genomic insertions and deletions are a potent source of functional variation, but are challenging to resolve with short-read sequencing, limiting knowledge of the role of such structural variants (SVs) in human evolution. Here, we used a graph-based method to genotype long-read-discovered SVs in short-read data from diverse human genomes. We then applied an admixture-aware method to identify 220 SVs exhibiting extreme patterns of frequency differentiation - a signature of local adaptation. The top two variants traced to the immunoglobulin heavy chain locus, tagging a haplotype that swept to near fixation in certain southeast Asian populations, but is rare in other global populations. Further investigation revealed evidence that the haplotype traces to gene flow from Neanderthals, corroborating the role of immune-related genes as prominent targets of adaptive introgression. Our study demonstrates how recent technical advances can help resolve signatures of key evolutionary events that remained obscured within technically challenging regions of the genome

TIGIT+Tfh show poor B-helper function and negatively correlate with SARS-CoV-2 antibody titre

Circulating follicular helper T cells (cTfh) can show phenotypic alterations in disease settings, including in the context of tissue-damaging autoimmune or anti-viral responses. Using severe COVID-19 as a paradigm of immune dysregulation, we have explored how cTfh phenotype relates to the titre and quality of antibody responses. Severe disease was associated with higher titres of neutralising S1 IgG and evidence of increased T cell activation. ICOS, CD38 and HLA-DR expressing cTfh correlated with serum S1 IgG titres and neutralising strength, and interestingly expression of TIGIT by cTfh showed a negative correlation. TIGIT+cTfh expressed increased IFNγ and decreased IL-17 compared to their TIGIT-cTfh counterparts, and showed reduced capacity to help B cells in vitro. Additionally, TIGIT+cTfh expressed lower levels of CD40L than TIGIT-cTfh, providing a potential explanation for their poor B-helper function. These data identify phenotypic changes in polyclonal cTfh that correlate with specific antibody responses and reveal TIGIT as a marker of cTfh with altered function

Evidence from MESSENGER for sulfur‐ and carbon‐driven explosive volcanism on Mercury

Targeted MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) X‐Ray Spectrometer measurements of Mercury's largest identified pyroclastic deposit are combined with neutron and reflectance spectroscopy data to constrain the composition of volatiles involved in the eruption that emplaced the pyroclastic material. The deposit, northeast of the Rachmaninoff basin, is depleted in S (relative to Ca and Si) and C, compared with the rest of Mercury's surface. Spectral reflectance measurements of the deposit indicate relatively high overall reflectance and an oxygen‐metal charge transfer (OMCT) absorption band at ultraviolet wavelengths. These results are consistent with oxidation of graphite and sulfides during magma ascent, via reaction with oxides in the magma or assimilated country rock, and the formation of S‐ and C‐bearing volatile species. Consumption of graphite during oxidation could account for the elevated reflectance of the pyroclastic material, and the strength of the OMCT band is consistent with ~0.03–0.1 wt % FeO in the deposit

The astrobiology primer: An outline of general knowledge - Version 1, 2006

Peer reviewe

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2

Abstract: Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating