The Positive Relationship between Moderate-to-Vigorous Physical Activity and Bone Mineral Content Is Not Mediated by Free Leptin Index in Prepubertal Children: The PANIC Study.

PURPOSE: Moderate-to-vigorous physical activity (MVPA) positively influences bone mineral content (BMC) in prepubertal children, but it is unknown whether this relationship is partially mediated by free leptin index. The aim of this study was to examine whether the relationship between MVPA and total body less head (TBLH) BMC is mediated or moderated by free leptin index in prepubertal children. METHODS: We performed a cross-sectional analysis on 401 children (194 girls) from baseline examinations of the Physical Activity and Nutrition in Childhood Study. We applied the four-way decomposition mediation analysis method to assess whether free leptin index, measured from fasted blood samples, mediated the relationship between accelerometer-measured MVPA and TBLH BMC measured by dual-energy X-ray absorptiometry. RESULTS: MVPA had a positive controlled direct effect on TBLH BMC in girls and boys (β = 0.010 to 0.011, p 0.05). CONCLUSION: Our study indicates that MVPA positively influences TBLH BMC through pathways not related to free leptin index in predominantly normal-weight prepubertal children, likely primarily through mechanical loading. The relationships between MVPA, free leptin index and TBLH BMC may be influenced by other factors such as pubertal status and adiposity, so it is unknown whether these observations extend to overweight and obese children at different stages of puberty

The Positive Relationship between Moderate-to-Vigorous Physical Activity and Bone Mineral Content Is Not Mediated by Free Leptin Index in Prepubertal Children: The PANIC Study.

PurposeModerate-to-vigorous physical activity (MVPA) positively influences bone mineral content (BMC) in prepubertal children, but it is unknown whether this relationship is partially mediated by free leptin index. The aim of this study was to examine whether the relationship between MVPA and total body less head (TBLH) BMC is mediated or moderated by free leptin index in prepubertal children.MethodsWe performed a cross-sectional analysis on 401 children (194 girls) from baseline examinations of the Physical Activity and Nutrition in Childhood Study. We applied the four-way decomposition mediation analysis method to assess whether free leptin index, measured from fasted blood samples, mediated the relationship between accelerometer-measured MVPA and TBLH BMC measured by dual-energy X-ray absorptiometry.ResultsMVPA had a positive controlled direct effect on TBLH BMC in girls and boys (β = 0.010 to 0.011, p p > 0.05).ConclusionOur study indicates that MVPA positively influences TBLH BMC through pathways not related to free leptin index in predominantly normal-weight prepubertal children, likely primarily through mechanical loading. The relationships between MVPA, free leptin index and TBLH BMC may be influenced by other factors such as pubertal status and adiposity, so it is unknown whether these observations extend to overweight and obese children at different stages of puberty

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Alien Registration- Porter, Josie H. (Skowhegan, Somerset County)

https://digitalmaine.com/alien_docs/4563/thumbnail.jp

Understanding, defining, engaging and evaluating secondary child sexual abuse prevention interventions

The first 2PS (Prevent & protect through support) Knowledge Transfer Workshop (KTW) was held with stakeholders on 22nd January 2024 at UWE in Bristol bringing together professionals, practitioners, academics, and policy makers from across Europe who work to prevent child sexual abuse. The KTW was the first of three that are spread across the three years of this Horizon Europe funded project and are the core dissemination and engagement activity for the project. As part of the 2PS project work package 2 (WP2) the KTW aims to create links with appropriate stakeholders and develop a stakeholder community consisting of experts and first-line responders to engage in knowledge exchange, raise awareness of prevention initiatives, and discuss best practice

The Positive Relationship between Moderate-to-Vigorous Physical Activity and Bone Mineral Content Is Not Mediated by Free Leptin Index in Prepubertal Children : The PANIC Study

Purpose: Moderate-to-vigorous physical activity (MVPA) positively influences bone mineral content (BMC) in prepubertal children, but it is unknown whether this relationship is partially mediated by free leptin index. The aim of this study was to examine whether the relationship between MVPA and total body less head (TBLH) BMC is mediated or moderated by free leptin index in prepubertal children. Methods: We performed a cross-sectional analysis on 401 children (194 girls) from baseline examinations of the Physical Activity and Nutrition in Childhood Study. We applied the four-way decomposition mediation analysis method to assess whether free leptin index, measured from fasted blood samples, mediated the relationship between accelerometer-measured MVPA and TBLH BMC measured by dual-energy X-ray absorptiometry. Results: MVPA had a positive controlled direct effect on TBLH BMC in girls and boys (β = 0.010 to 0.011, p 0.05). Conclusion: Our study indicates that MVPA positively influences TBLH BMC through pathways not related to free leptin index in predominantly normal-weight prepubertal children, likely primarily through mechanical loading. The relationships between MVPA, free leptin index and TBLH BMC may be influenced by other factors such as pubertal status and adiposity, so it is unknown whether these observations extend to overweight and obese children at different stages of puberty.peerReviewe

Analysis of cytochrome b5 reductase-mediated metabolism in the phytopathogenic fungus Zymoseptoria tritici reveals novel functionalities implicated in virulence

AbstractSeptoria tritici blotch (STB) caused by the Ascomycete fungus Zymoseptoria tritici is one of the most economically damaging diseases of wheat worldwide. Z. tritici is currently a major target for agricultural fungicides, especially in temperate regions where it is most prevalent. Many fungicides target electron transfer enzymes because these are often important for cell function. Therefore characterisation of genes encoding such enzymes may be important for the development of novel disease intervention strategies. Microsomal cytochrome b5 reductases (CBRs) are an important family of electron transfer proteins which in eukaryotes are involved in the biosynthesis of fatty acids and complex lipids including sphingolipids and sterols. Unlike the model yeast Saccharomyces cerevisiae which possesses only one microsomal CBR, the fully sequenced genome of Z. tritici bears three possible microsomal CBRs. RNA sequencing analysis revealed that ZtCBR1 is the most highly expressed of these genes under all in vitro and in planta conditions tested, therefore ΔZtCBR1 mutant strains were generated through targeted gene disruption. These strains exhibited delayed disease symptoms on wheat leaves and severely limited asexual sporulation. ΔZtCBR1 strains also exhibited aberrant spore morphology and hyphal growth in vitro. These defects coincided with alterations in fatty acid, sphingolipid and sterol biosynthesis observed through GC–MS and HPLC analyses. Data is presented which suggests that Z. tritici may use ZtCBR1 as an additional electron donor for key steps in ergosterol biosynthesis, one of which is targeted by azole fungicides. Our study reports the first functional characterisation of CBR gene family members in a plant pathogenic filamentous fungus. This also represents the first direct observation of CBR functional ablation impacting upon fungal sterol biosynthesis