Screening for low energy availability in male athletes : Attempted validation of LEAM-Q

A questionnaire-based screening tool for male athletes at risk of low energy availability (LEA) could facilitate both research and clinical practice. The present options rely on proxies for LEA such screening tools for disordered eating, exercise dependence, or those validated in female athlete populations. in which the female-specific sections are excluded. To overcome these limitations and support progress in understanding LEA in males, centres in Australia, Norway, Denmark, and Sweden collaborated to develop a screening tool (LEAM-Q) based on clinical investigations of elite and sub-elite male athletes from multiple countries and ethnicities, and a variety of endurance and weight-sensitive sports. A bank of questions was developed from previously validated questionnaires and expert opinion on various clinical markers of LEA in athletic or eating disorder populations, dizziness, thermoregulation, gastrointestinal symptoms, injury, illness, wellbeing, recovery, sleep and sex drive. The validation process covered reliability, content validity, a multivariate analysis of associations between variable responses and clinical markers, and Receiver Operating Characteristics (ROC) curve analysis of variables, with the inclusion threshold being set at 60% sensitivity. Comparison of the scores of the retained questionnaire variables between subjects classified as cases or controls based on clinical markers of LEA revealed an internal consistency and reliability of 0.71. Scores for sleep and thermoregulation were not associated with any clinical marker and were excluded from any further analysis. Of the remaining variables, dizziness, illness, fatigue, and sex drive had sufficient sensitivity to be retained in the questionnaire, but only low sex drive was able to distinguish between LEA cases and controls and was associated with perturbations in key clinical markers and questionnaire responses. In summary, in this large and international cohort, low sex drive was the most effective self-reported symptom in identifying male athletes requiring further clinical assessment for LEA

Impact of menstrual function on hormonal response to repeated bouts of intense exercise

Background: Strenous exercise stimulates the hypothalamic-pituitary (HP) axis in order to ensure homeostasis and promote anabolism. Furthermore, exercise stimulates a transient increase in the neurotrophin brain-derived neurotrophic factor (BDNF) suggested to mediate the anxiolytic effects of exercise. Athletes with secondary functional hypothalamic amenorrhea (FHA) have been reported to have lower BDNF, and a blunted HP axis response to exercise as athletes with overtraining syndrome. Aim: The aim of the study was to investigate the hormonal and BDNF responses to a two-bout maximal exercise protocol with four hours of recovery in between in FHA and eumenorrheic (EUM) athletes. Methods: Eumenorrheic (n = 16) and FHA (n = 14) endurance athletes were recruited from national teams and competitive clubs. Protocols included gynecological examination; body composition (DXA); 7-day assessment of energy availability; blood sampling pre and post the two exercises tests. Results: There were no differences between groups in hormonal responses to the first exercise bout. After the second exercise bout IGFBP-3 increased more in FHA compared with EUM athletes (2.1 ± 0.5 vs. 0.6 ± 0.6 μg/L, p = 0.048). There were non-significant trends toward higher increase in IGF-1 (39.3 ± 4.3 vs. 28.0 ± 4.6 μg/L, p = 0.074), BDNF (96.5 ± 22.9 vs. 34.4 ± 23.5 μg/L, p = 0.058), GH to cortisol ratio (0.329 ± 0.010 vs. 0.058 ± 0.010, p = 0.082), and decrease in IGF-1 to IGFBP-3 ratio (−2.04 ± 1.2 vs. 0.92 ± 1.22, p = 0.081) in athletes with FHA compared with EUM athletes. Furthermore, there was a non-significant trend toward a higher increase in prolactin to cortisol ratio in EUM athletes compared with athletes with FHA (0.60 ± 0.15 vs. 0.23 ± 0.15, p = 0.071). No differences in the hormonal or BDNF responses between the two exercise bouts as a result of menstrual function were found. Conclusion: No major differences in the hormonal or BDNF responses between the two exercise bouts as a result of menstrual function could be detected

Short-term effects and long-term changes of FUEL—a digital sports nutrition intervention on REDs related symptoms in female athletes

Female endurance athletes are at high risk for developing Relative Energy Deficiency in Sport (REDs), resulting in symptoms such as menstrual dysfunction and gastrointestinal (GI) problems. The primary aim of this study was to investigate effects of the FUEL (Food and nUtrition for Endurance athletes—a Learning program) intervention consisting of weekly online lectures combined with individual athlete-centered nutrition counseling every other week for sixteen weeks on REDs related symptoms in female endurance athletes at risk of low energy availability [Low Energy Availability in Females Questionnaire (LEAF-Q) score ≥8]. Female endurance athletes from Norway (n = 60), Sweden (n = 84), Ireland (n = 17), and Germany (n = 47) were recruited. Fifty athletes with risk of REDs (LEAF-Q score ≥8) and with low risk of eating disorders [Eating Disorder Examination Questionnaire (EDE-Q) global score <2.5], with no use of hormonal contraceptives and no chronic diseases, were allocated to either the FUEL intervention (n = 32) (FUEL) or a sixteen-week control period (n = 18) (CON). All but one completed FUEL and n = 15 completed CON. While no evidence for difference in change in LEAF-Q total or subscale scores between groups was detected post-intervention (BFincl < 1), the 6- and 12-months follow-up revealed strong evidence for improved LEAF-Q total (BFincl = 123) and menstrual score (BFincl = 840) and weak evidence for improved GI-score (BFincl = 2.3) among FUEL athletes. In addition, differences in change between groups was found for EDE-Q global score post-intervention (BFincl = 1.9). The reduction in EDE-Q score remained at 6- and 12- months follow-up among FUEL athletes. Therefore, the FUEL intervention may improve REDs related symptoms in female endurance athletes.Clinical Trial Registrationwww.clinicaltrials.gov (NCT04959565)

Predisposition to Childhood Otitis Media and Genetic Polymorphisms within the Toll-Like Receptor 4 (TLR4) Locus

Background Predisposition to childhood otitis media (OM) has a strong genetic component, with polymorphisms in innate immunity genes suspected to contribute to risk. Studies on several genes have been conducted, but most associations have failed to replicate in independent cohorts. Methods We investigated 53 gene polymorphisms in a Finnish cohort of 624 cases and 778 controls. A positive association signal was followed up in a tagging approach and tested in an independent Finnish cohort of 205 cases, in a British cohort of 1269 trios, as well as in two cohorts from the United States (US); one with 403 families and the other with 100 cases and 104 controls. Results In the initial Finnish cohort, the SNP rs5030717 in the TLR4 gene region showed significant association (OR 1.33, P=.003) to OM. Tagging SNP analysis of the gene found rs1329060 (OR 1.33, P=.002) and rs1329057 (OR 1.29, P=.003) also to be associated. In the more severe phenotype the association was stronger. This finding was supported by an independent Finnish case cohort, but the associations failed to replicate in the British and US cohorts. In studies on TLR4 signaling in 20 study subjects, the three-marker risk haplotype correlated with a decreased TNF alpha secretion in myeloid dendritic cells. Conclusions The TLR4 gene locus, regulating the innate immune response, influences the genetic predisposition to childhood OM in a subpopulation of patients. Environmental factors likely modulate the genetic components contributing to the risk of OM.Peer reviewe

Maternal Colonization With Group B Streptococcus and Serotype Distribution Worldwide: Systematic Review and Meta-analyses.

Background: Maternal rectovaginal colonization with group B Streptococcus (GBS) is the most common pathway for GBS disease in mother, fetus, and newborn. This article, the second in a series estimating the burden of GBS, aims to determine the prevalence and serotype distribution of GBS colonizing pregnant women worldwide. Methods: We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus), organized Chinese language searches, and sought unpublished data from investigator groups. We applied broad inclusion criteria to maximize data inputs, particularly from low- and middle-income contexts, and then applied new meta-analyses to adjust for studies with less-sensitive sampling and laboratory techniques. We undertook meta-analyses to derive pooled estimates of maternal GBS colonization prevalence at national and regional levels. Results: The dataset regarding colonization included 390 articles, 85 countries, and a total of 299924 pregnant women. Our adjusted estimate for maternal GBS colonization worldwide was 18% (95% confidence interval [CI], 17%-19%), with regional variation (11%-35%), and lower prevalence in Southern Asia (12.5% [95% CI, 10%-15%]) and Eastern Asia (11% [95% CI, 10%-12%]). Bacterial serotypes I-V account for 98% of identified colonizing GBS isolates worldwide. Serotype III, associated with invasive disease, accounts for 25% (95% CI, 23%-28%), but is less frequent in some South American and Asian countries. Serotypes VI-IX are more common in Asia. Conclusions: GBS colonizes pregnant women worldwide, but prevalence and serotype distribution vary, even after adjusting for laboratory methods. Lower GBS maternal colonization prevalence, with less serotype III, may help to explain lower GBS disease incidence in regions such as Asia. High prevalence worldwide, and more serotype data, are relevant to prevention efforts

Genetic predisposition to mosaic Y chromosome loss in blood.

Mosaic loss of chromosome Y (LOY) in circulating white blood cells is the most common form of clonal mosaicism1-5, yet our knowledge of the causes and consequences of this is limited. Here, using a computational approach, we estimate that 20% of the male population represented in the UK Biobank study (n = 205,011) has detectable LOY. We identify 156 autosomal genetic determinants of LOY, which we replicate in 757,114 men of European and Japanese ancestry. These loci highlight genes that are involved in cell-cycle regulation and cancer susceptibility, as well as somatic drivers of tumour growth and targets of cancer therapy. We demonstrate that genetic susceptibility to LOY is associated with non-haematological effects on health in both men and women, which supports the hypothesis that clonal haematopoiesis is a biomarker of genomic instability in other tissues. Single-cell RNA sequencing identifies dysregulated expression of autosomal genes in leukocytes with LOY and provides insights into why clonal expansion of these cells may occur. Collectively, these data highlight the value of studying clonal mosaicism to uncover fundamental mechanisms that underlie cancer and other ageing-related diseases.This research has been conducted using the UK Biobank Resource under application 9905 and 19808. This work was supported by the Medical Research Council [Unit Programme number MC_UU_12015/2]. Full study-specific and individual acknowledgements can be found in the supplementary information

Planck 2013 results. XXI. Power spectrum and high-order statistics of the Planck all-sky Compton parameter map

Peer reviewe

Planck 2013 results. XVI. Cosmological parameters

Peer reviewe

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat