Be Healthy in Pregnancy: Exploring factors that impact pregnant women\u27s nutrition and exercise behaviours

Excess gestational weight gain is associated with short- and long-term pregnancy complications. Although a healthy diet and physical activity during pregnancy are recommended and shown to reduce the risk of complications and improve outcomes, adherence to these recommendations is low. The aims of this study were to explore women\u27s view of nutrition and physical activity during pregnancy and to describe barriers and facilitators experienced in implementing physical activity and nutrition recommendations. In a substudy of the Be Healthy in Pregnancy randomized trial, 20 semistructured focus groups were conducted with 66 women randomized to the control group when they were between 16 and 24 weeks gestation. Focus groups were recorded, transcribed verbatim, coded and thematically analysed. The results indicate that women felt motivated to be healthy for their baby, but competing priorities may take precedence. Participants described limited knowledge and access to information on safe physical activity in pregnancy and lacked the skills needed to operationalize both physical activity and dietary recommendations. Women\u27s behaviours regarding diet and physical activity in pregnancy were highly influenced by their own and their peers\u27 beliefs and values regarding how weight gain impacted their health during pregnancy. Pregnancy symptoms beyond women\u27s control such as fatigue and nausea made physical activity and healthy eating more challenging. Counselling from care providers about nutrition and physical activity was perceived as minimal and ineffective. Future interventions should address improving counselling strategies and address individual\u27s beliefs around nutrition and activity in pregnancy

Galactic populations of radio and gamma-ray pulsars in the polar cap model

We simulate the characteristics of the Galactic population of radio and $\gamma$-ray pulsars using Monte Carlo techniques. At birth, neutron stars are spatially distributed in the Galactic disk, with supernova-kick velocities, and randomly dispersed in age back to $10^9$ years. They are evolved in the Galactic gravitational potential to the present time. From a radio luminosity model, the radio flux is filtered through a selected set of radio-survey parameters. $\gamma$-ray luminosities are assigned using the features of recent polar cap acceleration models invoking space-charge-limited flow, and a pulsar death valley further attenuates the population of radio-loud pulsars. Assuming a simple emission geometry with aligned radio and $\gamma$-ray beams of 1 steradian solid angle, our model predicts that EGRET should have seen 7 radio-loud and 1 radio-quiet, $\gamma$-ray pulsars. With much improved sensitivity, GLAST, on the other hand, is expected to observe 76 radio-loud and 74 radio-quiet, $\gamma$-ray pulsars of which 7 would be identified as pulsed sources. We also explore the effect of magnetic field decay on the characteristics of the radio and $\gamma$-ray pulsar populations. Including magnetic field decay on a timescale of 5 Myr improves agreement with the radio pulsar population and increases the predicted number of GLAST detected pulsars to 90 radio-loud and 101 radio-quiet (9 pulsed) $\gamma$-ray pulsars. The lower flux threshold allows GLAST to detect $\gamma$-ray pulsars at larger distances than those observed by the radio surveys used in this study.Comment: 38 pages, 11 figures, accepted for publication v565 n1 Ap

Experiences regarding nutrition and exercise among women during early postpartum: A qualitative grounded theory study

Background: Excess gestational weight gain has long- and short-term implications for women and children, and postpartum weight retention is associated with an increased risk of long-term obesity. Despite the existence of dietary and exercise guidelines, many women struggle to return to pre-pregnancy weight. Experiences of women in tackling postpartum weight loss are poorly understood. We undertook this study to explore experiences related to nutrition, exercise and weight in the postpartum in women in Ontario, Canada. Methods: This was a nested qualitative study within The Be Healthy in Pregnancy Study, a randomized controlled trial. Women randomized to the control group were invited to participate. Semi-structured focus groups were conducted at 4-6 months postpartum. Focus groups were audio recorded, transcribed verbatim, coded and analyzed thematically using a constructivist grounded theory approach. Results: Women experienced a complex relationship with their body image, due to unrealistic expectations related to their postpartum body. Participants identified barriers and enablers to healthy habits during pregnancy and postpartum. Gestational weight gain guidelines were regarded as unhelpful and unrealistic. A lack of guidance and information about weight management, healthy eating, and exercise in the postpartum period was highlighted. Conclusion: Strategies for weight management that target the unique characteristics of the postpartum period have been neglected in research and in patient counselling. Postpartum women may begin preparing for their next pregnancy and support during this period could improve their health for subsequent pregnancies

All-sky Medium Energy Gamma-ray Observatory: Exploring the Extreme Multimessenger Universe

The All-sky Medium Energy Gamma-ray Observatory (AMEGO) is a probe class mission concept that will provide essential contributions to multimessenger astrophysics in the late 2020s and beyond. AMEGO combines high sensitivity in the 200 keV to 10 GeV energy range with a wide field of view, good spectral resolution, and polarization sensitivity. Therefore, AMEGO is key in the study of multimessenger astrophysical objects that have unique signatures in the gamma-ray regime, such as neutron star mergers, supernovae, and flaring active galactic nuclei. The order-of-magnitude improvement compared to previous MeV missions also enables discoveries of a wide range of phenomena whose energy output peaks in the relatively unexplored medium-energy gamma-ray band

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Hand osteoarthritis: clinical phenotypes, molecular mechanisms and disease management

Osteoarthritis (OA) is a highly prevalent condition and the hand is the most commonly affected site. Patients with hand OA frequently report symptoms of pain, functional limitations, and frustration in undertaking everyday activities. The condition presents clinically with changes to the bone, ligaments, cartilage and synovial tissue, which can be observed using radiography, ultrasonography or MRI. Hand OA is a heterogeneous disorder and is considered to be multifactorial in aetiology. This review provides an overview of the epidemiology, presentation and burden of hand OA, including an update on hand OA imaging (including the development of novel techniques), disease mechanisms and management. In particular, areas for which new evidence has substantially changed the way we understand, consider and treat hand OA are highlighted. For example, genetic studies, clinical trials and careful prospective imaging studies from the past 5 years are beginning to provide insights into the pathogenesis of hand OA that might uncover new therapeutic targets in disease

Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

11 páginas, 4 figuras, 2 tablas. Datasets en su material suplementario. This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2302720120/-/DCSupplemental.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.This work was supported by the Michael J. Fox Foundation grant MJFF-020161 (E.M., Z.G.-O.), NIH and National Institute of Aging grants AG060747 (M.D.G.), AG066206 (Z.H.), AG066515 (Z.H., M.D.G.), the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie (grant agreement No. 890650, Y.L.G.), the Alzheimer’s Association (AARF-20-683984, M.E.B.), and the Iqbal Farrukh and Asad Jamal Fund, a grant from the EU Joint Programme—Neurodegenerative Disease Research (European Alzheimer DNA BioBank, EADB; JPND), the Japan Agency for Medical Research and Development JP21dk0207045 (T.I.), JP21dk020704 (K.O., S.N.), JP21km040550 (K.O.), the Einstein Center for Neurosciences in Berlin (S.M.Y.), the Swedish Research Council (#2018-02532, H.Z.), the European Research Council (#681712, H.Z.), and the Swedish State Support for Clinical Research (#ALFGBG-720931, H.Z.). Inserm UMR1167 is also funded by the Inserm, Institut Pasteur de Lille, Lille Métropole Communauté Urbaine, and the French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Additional funders of individual investigators and institutions who contributed to data collection and genotyping are provided in SI Appendix.Peer reviewe