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Aim Methods Results Conclusion Research has indicated a rise in the prevalence of depression and anxiety among adolescents over the past three decades. However, the factors underpinning increases in mental health difficulties remain poorly understood. This study examines psychological, social and environmental risk and protective factors that may explain changes in depression and anxiety among adolescents.Data were taken from two nationally representative My World Surveys of adolescents aged 12–19 years in 2012 (N = 5,490) and 2019 (N = 9,844). Survey data on depression and anxiety and a range of potential risk (e.g., alcohol use, psychotic symptoms) and protective factors (e.g., resilience, self‐esteem) were assessed at both time points. Multiple group analyses assessed whether the predictive ability of risk/protective factors changed from wave 1 to wave 2.Results showed that the prevalence of depression and anxiety increased significantly between 2012 and 2019, particularly among females. Predictors accounted for between 37% and 61% of the variance in outcomes across waves. While some risk/protective factors were consistent predictors of depression and anxiety at both waves (e.g., bullying, discrimination, optimism), reporting female gender and having higher formal help‐seeking tendencies more strongly predicted anxiety at wave 2, while lower self‐esteem and lower resilience (personal competence) strongly predicted both depression and anxiety at wave 2.Findings highlight the need to prioritize adolescent mental health service provision, especially in females. Self‐esteem and resilience are potentially important targets for supporting adolescent mental health. Further research is required to understand the causal factors associated with increases in anxiety and depression. [ABSTRACT FROM AUTHOR]

Background: Poor body image is prevalent among adolescents and associated with several negative outcomes for their physical and psychological health. There is a pressing need to address this growing public health concern, yet there are few evidence-informed universal programmes for older adolescents that address contemporary body image concerns (i.e., social media). BodyKind is a four lesson, school-based, teacher led, universal body image programme that incorporates empirically supported principles of cognitive dissonance, self-compassion, compassion for others and social activism, to support positive body image development. Building on previous pilot trials in the USA, this paper outlines the protocol for a cluster randomised control trial (cRCT) and implementation evaluation of the BodyKind programme which was culturally adapted for the Irish cultural context. Methods: We aim to recruit 600 students aged 15-17 years in Transition Year (4th year) across 26 second-level schools in Ireland. Using minimisation, schools will be randomly assigned to receive BodyKind (intervention condition, n=300) or classes as usual (waitlist control, n=300). Teachers in intervention groups will receive training and deliver the programme to students over four weeks, at a rate of one lesson per week. Primary outcomes of body appreciation, body dissatisfaction and psychological wellbeing and secondary outcomes of self-compassion, compassion for others, body ideal internalisation, social justice motives and appearance-based social media use will be assessed at pre-, post- and 2 month follow up. Mediation and moderation analyses will be conducted to identify how and for whom the intervention works best. An implementation evaluation will assess the quality of programme implementation across schools and how this may influence intervention outcomes. Waitlist control schools will receive the programme after the 2-month follow up. Conclusion: This study will be the first to implement a cRCT and an implementation evaluation to assess the impact of this multicomponent school-based body image programme designed to support healthy body image development. If shown to be effective, BodyKind will have the potential to improve adolescent body image and wellbeing and inform efforts to implement sustainable and scalable programmes in schools. Trial registration: The trial was retrospectively registered on 10/10/2023 on ClinicalTrials.gov NCT06076993. [ABSTRACT FROM AUTHOR]

Aims: Sexual minority youth experience health disparities across mental, physical and sexual domains. However, little is known about the extent to which mental health overlaps with sexual and physical health to compound health problems among sexual minority youth. This study examined risky health behaviours, adverse health outcomes, and their overlap across mental, physical and sexual domains, in lesbian, gay, bisexual, questioning (LGBQ) and heterosexual third‐level students in Ireland. Method: Cross‐sectional data from the My World Survey 2‐Post Second Level (MWS2‐PSL) were used. Analyses were conducted on data from N = 7950 18–25‐year‐old students, of which 6204 (78%) identified as heterosexual, 910 (11.4%) bisexual, 412 (5.2%) lesbian/gay and 424 (5.3%) questioning. Risky health behaviours (e.g., self‐harm), adverse outcomes (e.g., mental health difficulties, physical health conditions) and their overlap across mental, physical and sexual domains were compared across heterosexual and LGBQ students using Chi‐square tests. Clustering of health behaviours/outcomes within and between domains were examined. Results: LGBQ students were more likely to exhibit a greater number of risky mental and sexual health behaviours and outcomes. Sexual, physical and mental health behaviours and outcomes overlapped to a greater extent in LGBQ versus heterosexual students. Distinct health outcomes were observed across sexual minority subgroups (e.g., bisexual women reported greater mental health difficulties). Conclusion: Findings demonstrate health inequalities experienced by LGBQ students, particularly across mental and sexual domains. Holistic integrated approaches that consider multiple health domains simultaneously and the distinct health needs of sexual minority subgroups are needed to promote greater health equity. [ABSTRACT FROM AUTHOR]

This experiment with 363 Irish and Flemish men aged 19 to 30 years (M = 23.56, SD = 2.36) investigated exposure to different male model ads (i.e. muscular, slim, plus-size, overall diversity, and no models) on well-being (i.e. body image, low body fat and muscularity attitudes, self-objectification, and self-esteem) and advertising outcomes (i.e. ad attitudes, brand attitudes, and purchase intent). Moderation effects of country and masculinity (i.e. dominance, winning) were investigated. The diversity condition generated more positive effects for low body fat attitudes than the muscular, slim, and no model conditions. Yet, no differences appeared for this outcome between the diversity and plus-size condition. No effects for the other well-being and advertising variables were found. Moderation analyses revealed higher purchase intent in the slim condition for men high in dominance. No effects were found for country and winning. Findings suggest that non-idealized models have protective effects for some men. [ABSTRACT FROM AUTHOR]

Body image, body change behaviours, and risk and protective factors for body esteem, were documented by sexual orientation in young adults aged 18–25 years. Cross-sectional data from My World Survey 2 Post Second Level (MWS2-PSL) were used. The sample consisted of 1,975 heterosexual, 256 gay, 169 bisexual, 89 questioning men and 4,521 heterosexual, 167 lesbian, 781 bisexual, 356 questioning and 121 pansexual women. Body esteem, body dissatisfaction and body change behaviours as well as sexual minority stress risk (discrimination) and protective factors (resilience) were analysed across groups using Chi Square Tests and Analyses of Covariance. Multiple regressions identified relationships between body esteem, body change behaviours and risk and protective factors. Heterosexual men exhibited higher body esteem and body satisfaction than sexual minority men. Bisexual women demonstrated the lowest body esteem, while pansexual women exhibited lower body satisfaction versus heterosexual, lesbian and questioning women. Body change behaviours did not differ among women, but weight loss attempts were elevated in gay and bisexual men. Comfort with sexuality, resilience and social support were positively associated with body esteem. Risk and protective factors for body esteem varied by sexual orientation, highlighting the importance of examining these constructs separately across sexual minority subgroups. [ABSTRACT FROM AUTHOR]

Introduction: Self-compassion interventions reduce body dissatisfaction in adults but have not been extensively investigated in adolescents. A novel 5-week Digital Social Media Adolescent Resilience Training intervention grounded in Gilbert's (2010) Compassionate Mind Training was adapted to address adolescent's social media-related body image concerns. Method: A convenience sample of 102 adolescents, 54 girls (53%), 48 boys (47%), aged 15–17 years (M =15.6, SD =0.46) were recruited from four mixed gender Irish Secondary Schools. Due to data loss because of Covid-19, analyses were conducted on data from 80 participants (24 boys, 56 girls). A mixed methods quasi-experimental design was used. Primary outcomes of self-compassion, self-criticism, social media comparisons and body image perceptions were quantitatively assessed at pre, post-intervention and 3-month follow up, while post-intervention focus groups qualitatively documented adolescents' responses to the programme. Results: Qualitative data indicated that the programme was feasible and acceptable. Analyses revealed significant increases in body appreciation and body satisfaction in the experimental group from pre- to post-intervention. Girls exhibited significant increases in body appreciation and reductions in self-criticism, while boys exhibited increases in body satisfaction. Improvements in body satisfaction were observed at 3-month follow up. Conclusions: Findings indicate that self-compassion has potential to improve adolescent's body image perceptions, but further research is warranted. [ABSTRACT FROM AUTHOR]

Research has documented relationships between individual health behaviours and mental health, but few studies have examined patterns of health behaviours (i.e., health lifestyles) and mental health outcomes. This study investigated the relationship between health lifestyles and mental health and psychological wellbeing in adolescents. Data from the My World Survey 2 - Second Level (MWS2-SL), a random national sample of 9493 adolescents (44.2% male) aged 12-18 years (M = 14.8, SD = 1.66) in second level education in Ireland were used. TwoStep cluster analysis identified clustering of health behaviours (sleep, alcohol use, cannabis use, social media use, sport and hobby participation). ANOVA and Chi Square tests identified potential differences in demographic characteristics (age, gender, socioeconomic status, ethnicity) and psychological outcomes (anxiety, depression, life satisfaction, daily functioning) across clusters. Three clusters were identified; 1. Low (22.0%), 2. Moderate-high (41.5%) and 3. High (36.5%), health promoting. The 'Low' health-promoting cluster, characterised by high alcohol, cannabis and social media use, moderate sport and hobby participation, and low sleep duration, demonstrated the highest levels of anxiety and depression and the lowest levels of life satisfaction, self-esteem and daily functioning. The 'High' health-promoting cluster reported the most favourable psychological outcomes. Cluster 1 were more likely to be older and male, Cluster 3 were more likely to be younger and female. Findings demonstrate the potential for health promotive lifestyles to mitigate mental health difficulties and promote life satisfaction and daily functioning in adolescents. Health lifestyles represent important indicators of mental health and targets for prevention/promotion efforts. [ABSTRACT FROM AUTHOR]

Abstract: We have generated large libraries of single-chain Fv antibody fragments (>1010 transformants) containing unbiased amino acid diversity that is restricted to the central combining site of the stable, well-expressed DP47 and DPK22 germline V-genes. Library WySH2A was constructed to examine the potential for synthetic complementarity-determining region (CDR)-H3 diversity to act as the lone source of binding specificity. Library WySH2B was constructed to assess the necessity for diversification in both the H3 and L3. Both libraries provided diverse, specific antibodies, yielding a total of 243 unique hits against 7 different targets, but WySH2B produced fewer hits than WySH2A when selected in parallel. WySH2A also consistently produced hits of similar quality to WySH2B, demonstrating that the diversification of the CDR-L3 reduces library fitness. Despite the absence of deliberate bias in the library design, CDR length was strongly associated with the number of hits produced, leading to a functional loop length distribution profile that mimics the biases observed in the natural repertoire. A similar trend was also observed for the CDR-L3. After target selections, several key amino acids were enriched in the CDR-H3 (e.g., small and aromatic residues) while others were reduced (e.g., strongly charged residues) in a manner that was specific to position, preferentially occurred in CDR-H3 stem positions, and tended towards residues associated with loop stabilization. As proof of principle for the WySH2 libraries to produce viable lead candidate antibodies, 114 unique hits were produced against Delta-like ligand 4 (DLL4). Leads exhibited nanomolar binding affinities, highly specific staining of DLL4+ cells, and biochemical neutralization of DLL4–NOTCH1 interaction. [Copyright &y& Elsevier]

Objectives: Severe coronavirus disease 2019 is associated with an extensive pneumonitis and frequent coagulopathy. We sought the true prevalence of thrombotic complications in critically ill patients with severe coronavirus disease 2019 on the ICU, with or without extracorporeal membrane oxygenation.Design: We undertook a single-center, retrospective analysis of 72 critically ill patients with coronavirus disease 2019-associated acute respiratory distress syndrome admitted to ICU. CT angiography of the thorax, abdomen, and pelvis were performed at admission as per routine institution protocols, with further imaging as clinically indicated. The prevalence of thrombotic complications and the relationship with coagulation parameters, other biomarkers, and survival were evaluated.Setting: Coronavirus disease 2019 ICUs at a specialist cardiorespiratory center.Patients: Seventy-two consecutive patients with coronavirus disease 2019 admitted to ICU during the study period (March 19, 2020, to June 23, 2020).Interventions: None.Measurements and Main Results: All but one patient received thromboprophylaxis or therapeutic anticoagulation. Among 72 patients (male:female = 74%; mean age: 52 ± 10; 35 on extracorporeal membrane oxygenation), there were 54 thrombotic complications in 42 patients (58%), comprising 34 pulmonary arterial (47%), 15 peripheral venous (21%), and five (7%) systemic arterial thromboses/end-organ embolic complications. In those with pulmonary arterial thromboses, 93% were identified incidentally on first screening CT with only 7% suspected clinically. Biomarkers of coagulation (e.g., d-dimer, fibrinogen level, and activated partial thromboplastin time) or inflammation (WBC count, C-reactive protein) did not discriminate between patients with or without thrombotic complications. Fifty-one patients (76%) survived to discharge; 17 (24%) patients died. Mortality was significantly greater in patients with detectable thrombus (33% vs 10%; p = 0.022).Conclusions: There is a high prevalence of thrombotic complications, mainly pulmonary, among coronavirus disease 2019 patients admitted to ICU, despite anticoagulation. Detection of thrombus was usually incidental, not predicted by coagulation or inflammatory biomarkers, and associated with increased risk of death. Systematic CT imaging at admission should be considered in all coronavirus disease 2019 patients requiring ICU. [ABSTRACT FROM AUTHOR]

The left atrial appendage (LAA) has a key role in the embolic complications of atrial fibrillation (AF). It has been studied extensively, from recent interest in the thrombotic implications of various LAA morphologies to LAA occlusion and ablation. We collected eleven post-mortem LAA samples for visual analysis, two were not included due to poor sample quality. On examination of the nine remaining samples, several common patterns of pectinate muscle orientation were noted. The LAA samples were noted to have a smooth circumferential neck of muscular tissue giving rise to a dominant singular smooth trunk of papillary muscle in 6 cases and two trunks in 3 cases. These trunks were either shallow (5 samples) or more muscular and raised (4 samples). Shallow trunks tended to be wider than the raised trunks and may even be circumferential (2 samples). The main trunk arborized to give off papillary muscle branches down to third or fourth order branches. The samples were visually assessed for the percentage of smooth papillary muscle versus non-papillary recesses and were found to have =50% smooth muscle in 3 samples, 50-75% in 3 samples and >75% in 3 samples. We performed histological analysis of further LAA samples collected during cardiac surgery in a parallel study. We identified a distinct pattern of myocyte orientation from the neck, mid-section and apical section of the LAA demonstrating arborization of myocyte fibers with minimal communication in distal segments of the LAA. We feel that this information may help understanding of the issues surrounding LAA ablation strategies. [ABSTRACT FROM AUTHOR]

Either due to the severity of disease of these patients, many of whom were on extracorporeal membrane oxygenation, or the fact that all patients systematically underwent contrast-enhanced CT at admission to ICU. The ideal investigational algorithm for screening patients admitted to ICU with COVID-19 ARDS remains elusive, as do unified anticoagulation treatment recommendations in the absence of confirmed thrombosis ([6]). The burden of thromboses in patients with COVID-19 ARDS requiring ICU was higher than pre-COVID-19 ARDS ([2]). [Extracted from the article]

Abstract: The ‘accuracy’ of age, blood pressure, clinical features, duration and diabetes (ABCD2) scoring by non-stroke specialists referring patients to a daily Rapid Access Stroke Prevention (RASP) service is unclear, as is the accuracy of ABCD2 scoring by trainee residents. In this prospective study, referrals were classified as ‘confirmed TIAs’ if the stroke specialist confirmed a clinical diagnosis of possible, probable or definite TIA, and ‘non-TIAs’ if patients had a TIA mimic or completed stroke. ABCD2 scores from referring physicians were compared with scores by experienced stroke specialists and neurology/geriatric medicine residents at a daily RASP clinic; inter-observer agreement was examined. Data from 101 referrals were analysed (mean age=60.0years, 58% male). The median interval between referral and clinic assessment was 1day. Of 101 referrals, 52 (52%) were ‘non-TIAs’: 45 (86%) of 52 were ‘TIA mimics’ and 7 (14%) of 52 were completed strokes. There was only ‘fair’ agreement in total ABCD2 scoring between referring physicians and stroke specialists (κ =0.37). Agreement was ‘excellent’ between residents and stroke specialists (κ =0.91). Twenty of 29 patients scored as ‘moderate to high risk’ (score 4–6) by stroke specialists were scored ‘low risk’ (score 0–3) by referring physicians. ABCD2 scoring by referring doctors is frequently inaccurate, with a tendency to underestimate stroke risk. These findings emphasise the importance of urgent specialist assessment of suspected TIA patients, and that ABCD2 scores by non-stroke specialists cannot be relied upon in isolation to risk-stratify patients. Inter-observer agreement in ABCD2 scoring was ‘excellent’ between residents and stroke specialists, indicating short-term training may improve accuracy. [Copyright &y& Elsevier]

Deoxycholic acid (DCA) is a secondary bile acid that modulates signalling pathways in epithelial cells. DCA has been implicated in pathogenesis of colon carcinoma, particularly by activation of the protein kinase C (PKC) pathway. Ursodeoxycholic acid (UDCA), a tertiary bile acid, has been observed to have chemopreventative effects. The aim of this study was to investigate the effect of DCA and UDCA on the subcellular localization and activity of PKCη and its downstream effects on Golgi structure in a colon cancer cell model. PKCη expression was localized to the Golgi in HCT116 colon cancer cells. DCA induced fragmentation of the Golgi in these cells following activation of PKCη and its downstream effector protein kinase D (PKD). Pretreatment of cells with UDCA or a glucocorticoid, dexamethasone, inhibited DCA-induced PKCη/PKD activation and Golgi fragmentation. Knockdown of glucocorticoid receptor (GR) expression using small interfering RNA or inhibition using the GR antagonist mifepristone attenuated the inhibitory effect of UDCA on Golgi fragmentation. Elevated serum and faecal levels of DCA have been previously reported in patients with ulcerative colitis (UC) and colon cancer. Analysis of Golgi architecture in vivo using tissue microarrays revealed Golgi fragmentation in UC and colorectal cancer tissue. We have demonstrated that DCA can disrupt the structure of the Golgi, an organelle critical for normal cell function. Inhibition of this DCA-induced Golgi fragmentation by UDCA was mediated via the GR. This represents a potential mechanism of observed chemopreventative effects of UDCA in benign and malignant disease of the colon. [ABSTRACT FROM PUBLISHER]

Summary: Antibodies that neutralize RAGE (receptor for advanced glycation end products)–ligand interactions have potential therapeutic applications in both acute and chronic diseases. We generated XT-M4, a rat anti-RAGE monoclonal antibody that has in vivo efficacy in an acute sepsis model. This antibody was subsequently humanized. To improve the affinity of this antibody for the treatment of chronic indications, we used random and targeted mutagenesis strategies in combination with ribosome and phage-display technologies, respectively, to generate libraries of XT-M4 variants. We identified a panel of single-chain Fv antibody fragments (scFv''s) that was improved up to 110-fold in a homogeneous time-resolved fluorescence competition assay against parental XT-M4 immunoglobulin G (IgG). After reformatting to bivalent scFv–Fc fusions and IgGs, we observed similar gains in potency in the same assay. Further analysis of binding kinetics as IgG revealed multiple variants with subnanomolar apparent affinity that was dictated primarily by improvements in the off-rate. All variants also had improved binding to cell surface-expressed human RAGE, and all retained, or had improved, apparent affinity for mouse RAGE. F100bL in VH (variable region of the heavy chain) complementarity-determining region 3 (CDR3) was one of a number of key mutations that correlated with affinity improvements and was independently identified by both mutagenesis strategies. Random mutagenesis coupled with ribosome display and high-throughput screening revealed an unexpectedly high level of mutational plasticity across the whole length of the humanized scFv, suggesting greater scope for structural optimization outside of the primary antigen-combining site defined by VH CDR3 and Vκ CDR3. In summary, our comprehensive mutagenesis approach not only achieved the desired affinity maturation of XT-M4 but also defined multiple mutational hotspots across the antibody sequence, provided an insight into the specificity-determining residues of the antibody paratope, and identified additional sites within the CDR loops where human germ-line amino acids may be introduced without affecting function. [Copyright &y& Elsevier]