Emotion in Motion: Weight Bias Internalization, Exercise Avoidance, and Fitness-Related Self-Conscious Emotions.

Weight bias internalization (WBI), the process of internalizing negative attitudes and stereotypes towards overweight individuals, significantly impacts self-worth and health behaviors, such as exercise avoidance. In the current study, we focused on the mediating role of fitness-related self-conscious emotions, particularly shame and guilt. A cross-sectional study involving 150 self-described overweight Dutch women (age M = 49.63 ± 10.72) was conducted online. Participants completed measures assessing weight bias internalization, exercise avoidance, and body/fitness-related self-conscious emotions. Data were analyzed using linear regression and mediation analysis, controlling for age, BMI, and exercise frequency. The results show that weight bias internalization, guilt-free shame, and shame-free guilt uniquely predict exercise avoidance. Guilt-free shame partially mediated the relationship between weight bias internalization and exercise avoidance, indicating that increased internalized weight bias led to higher levels of guilt-free shame, which in turn contributed to exercise avoidance. Shame-free guilt did not act as a unique mediator. These findings underscore the importance of addressing weight bias internalization and fitness-related self-conscious emotions, particularly guilt-free shame, in interventions targeting exercise avoidance among overweight individuals. Strategies promoting self-compassion and reducing shame may prove beneficial in improving exercise behaviors and overall well-being.

Hotspot DNA Methyltransferase 3A (DNMT3A) and Isocitrate Dehydrogenase 1 and 2 (IDH1/2) Mutations in Acute Myeloid Leukemia and Their Relevance as Targets for Immunotherapy.

DNA methyltransferase 3A (DNMT3A) and isocitrate dehydrogenase 1 and 2 (IDH1/2) are genes involved in epigenetic regulation, each mutated in 7-23% of patients with acute myeloid leukemia. Here, we investigated whether hotspot mutations in these genes encode neoantigens that can be targeted by immunotherapy. Five human B-lymphoblastoid cell lines expressing common HLA class I alleles were transduced with a minigene construct containing mutations that often occur in DNMT3A or IDH1/2. From these minigene-transduced cell lines, peptides were eluted from HLA class I alleles and analyzed using tandem mass spectrometry. The resulting data are available via ProteomeXchange under the identifier PXD050560. Mass spectrometry revealed an HLA-A*01:01-binding DNMT3AR882H peptide and an HLA-B*07:02-binding IDH2R140Q peptide as potential neoantigens. For these neopeptides, peptide-HLA tetramers were produced to search for specific T-cells in healthy individuals. Various T-cell clones were isolated showing specific reactivity against cell lines transduced with full-length DNMT3AR882H or IDH2R140Q genes, while cell lines transduced with wildtype genes were not recognized. One T-cell clone for DNMT3AR882H also reacted against patient-derived acute myeloid leukemia cells with the mutation, while patient samples without the mutation were not recognized, thereby validating the surface presentation of a DNMT3AR882H neoantigen that can potentially be targeted in acute myeloid leukemia via immunotherapy.

Racial Disparities in Glaucoma Vision Outcomes and Eye Care Utilization: An IRIS Registry Analysis.

PURPOSE: To evaluate racial disparities in vision outcomes and eye care utilization among glaucoma patients. DESIGN: Retrospective cohort study. METHODS: In this population-based IRIS Registry (Intelligent Research in Sight) study, we included patients with minimum one diagnosis code for glaucoma at least 6 months prior to January 1, 2015 and at least one eye exam, visual field (VF), optical coherence tomography (OCT), or eye-related inpatient or emergency department (ED) code in 2015. Multivariable logistic and negative binomial regression models were used to assess vision and utilization outcomes, respectively, across race and ethnicity from January 1, 2015 to January 1, 2020. Vision outcomes included cup-to-disc ratio (CDR) progression > 0.80, poor vision (visual acuity 20/200 or worse), low vision codes, and need for glaucoma filtering surgery. Utilization outcomes included outpatient eye exams, OCTs, VFs, inpatient/ED encounters, and lasers/surgeries. RESULTS: Among 996,297 patients, 73% were non-Hispanic White, 15% non-Hispanic Black, 9% Hispanic, 3% Asian/Pacific Islander, and 0.3% Native American/Alaska Native. Compared to White eyes, Black and Hispanic eyes had higher adjusted odds of CDR progression (odds ratio [OR] = 1.12, 95% confidence interval [CI] = 1.08-1.17; OR = 1.28, 95% CI = 1.22-1.34), poor vision (OR = 1.26, 95% CI = 1.22-1.29; OR = 1.26, 95% CI = 1.22-1.31), glaucoma filtering surgery (rate ratio (RR) = 1.47, 95% CI = 1.42-1.51; RR = 1.13, 95% CI = 1.09-1.18). Hispanic eyes also had increased odds of low vision diagnoses (Hispanic OR = 1.18, 95% CI = 1.07-1.30). Black and Hispanic patients were less likely to have eye exams (RR = 0.94, 95% CI = 0.94-0.95; RR = 0.99, 95% CI = 0.99-0.99) and OCTs (RR = 0.86, 95% CI = 0.85-0.86; RR = 0.97, 95% CI = 0.96-0.98), yet Black patients had higher odds of inpatient/ED encounters (RR = 1.64, 95% CI = 1.37-1.96) compared to White patients. Native American patients were more likely to have poor vision (OR = 1.17, 95% CI = 1.01-1.36) and less likely to have outpatient visits (RR = 0.89, 95% CI = 0.86-0.91), OCTs (RR = 0.85, 95% CI = 0.82-0.89), visual fields (RR = 0.91, 95% CI = 0.88-0.94) or lasers/surgeries (RR = 0.87, 95% CI = 0.79-0.96) compared to White patients. CONCLUSIONS: We found that significant disparities in US eye care exist with Black, Hispanic, and Native American patients having worse vision outcomes and less disease monitoring. Glaucoma may be undertreated in these racial and ethnic minority groups, increasing risk for glaucoma-related vision loss.

Machine Learning-Derived Baseline Visual Field Patterns Predict Future Glaucoma Onset in the Ocular Hypertension Treatment Study.

Purpose: The Ocular Hypertension Treatment Study (OHTS) identified risk factors for primary open-angle glaucoma (POAG) in patients with ocular hypertension, including pattern standard deviation (PSD). Archetypal analysis, an unsupervised machine learning method, may offer a more interpretable approach to risk stratification by identifying patterns in baseline visual fields (VFs). Methods: There were 3272 eyes available in the OHTS. Archetypal analysis was applied using 24-2 baseline VFs, and model selection was performed with cross-validation. Decomposition coefficients for archetypes (ATs) were calculated. A penalized Cox proportional hazards model was implemented to select discriminative ATs. The AT model was compared to the OHTS model. Associations were identified between ATs with both POAG onset and VF progression, defined by mean deviation change per year. Results: We selected 8494 baseline VFs. Optimal AT count was 19. The highest prevalence ATs were AT9, AT11, and AT7. The AT-based prediction model had a C-index of 0.75 for POAG onset. Multivariable models demonstrated that a one-interquartile range increase in the AT5 (hazard ratio [HR] = 1.14; 95% confidence interval [CI], 1.04-1.25), AT8 (HR = 1.22; 95% CI, 1.09-1.37), AT15 (HR = 1.26; 95% CI, 1.12-1.41), and AT17 (HR = 1.17; 95% CI, 1.03-1.31) coefficients conferred increased risk of POAG onset. AT5, AT10, and AT14 were significantly associated with rapid VF progression. In a subgroup analysis by high-risk ATs (>95th percentile or <75th percentile coefficients), PSD lost significance as a predictor of POAG in the low-risk group. Conclusions: Baseline VFs, prior to detectable glaucomatous damage, contain occult patterns representing early changes that may increase the risk of POAG onset and VF progression in patients with ocular hypertension. The relationship between PSD and POAG is modified by the presence of high-risk patterns at baseline. An AT-based prediction model for POAG may provide more interpretable glaucoma-specific information in a clinical setting.

Association between antidepressant use during pregnancy and miscarriage: a systematic review and meta-analysis.

BACKGROUND: Literature surrounding the association between antidepressant use during pregnancy and miscarriage is conflicting. We aimed to conduct a systematic review and meta-analysis of studies among pregnant women regarding the association between exposure to antidepressants during pregnancy and the risk of miscarriage, compared with pregnant women not exposed to antidepressants. DESIGN: We conducted a systematic review and meta-analysis of non-randomised studies. DATA SOURCES: We searched Medline, Embase and PsychINFO up to 6 August 2023. ELIGIBILITY CRITERIA AND OUTCOMES: Case-control, cohort and cross-sectional study designs were selected if they compared individuals exposed to any antidepressant class during pregnancy to comparator groups of either no antidepressant use or an alternate antidepressant. DATA EXTRACTION AND SYNTHESIS: Effect estimates were extracted from selected studies and pooled using a random-effects meta-analysis. Risk of bias (RoB) was assessed using the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool, and heterogeneity assessed using the I2 statistic. Subgroup analyses were used to explore antidepressant classes and the impact of confounding by indication. RESULTS: 1800 records were identified from the search, of which 29 were included in the systematic review and meta-analysis. The total sample included 5 671 135 individuals. Antidepressant users initially appeared to have a higher risk of miscarriage compared with unexposed individuals from the general population (summary effect estimate: 1.24, 95% CI 1.18 to 1.31, I2=69.2%; number of studies (n)=29). However, the summary estimate decreased when comparing against unexposed individuals with maternal depression (1.16, 1.04 to 1.31; I2=58.6%; n=6), suggesting confounding by indication may be driving the association. 22 studies suffered from serious RoB, and only two of the 29 studies were deemed at moderate RoB. CONCLUSIONS: After accounting for maternal depression, there is little evidence of any association between antidepressant use during pregnancy and miscarriage. Instead, the results indicate the biasing impact of confounding by indication.

Provision of online eye movement and desensitisation therapy (EMDR) for people with post-traumatic stress disorder (PTSD): a multi-method service evaluation.

Background: The evidence for the effectiveness of online EMDR for PTSD is scarce.Objective: This service evaluation aimed to assess how online EMDR compared to in-person EMDR, in terms of its potential effectiveness and acceptability to therapists and patients.Method: The evaluation was carried out in the Cardiff and Vale University Health Board Traumatic Stress Service. We compared the outcome of therapy (PTSD scores at end of treatment), number of sessions, drop-out rate, and adverse events using linear/logistic regression in those receiving online EMDR over a 12-month period with those who had received in-person therapy in the year previous to that. Interviews with therapists and clients who had provided or undertaken online EMDR explored their views and experiences of treatment. Interviews were analysed thematically.Results: 33 people received in-person EMDR (15.3 sessions, SD = 1.4), and 45 received online EMDR (12.4 sessions, SD = 0.9). 24 individuals completed therapy in-person, and 32 online. There was no evidence of a difference in therapy completion, drop-out rates or adverse events between the two delivery modes. There was weak evidence that those who completed EMDR online and had available data (N = 29), had slightly lower PTSD scores at the end of therapy compared to those who received in-person EMDR (N = 24) (17.1 (SD = 3.2) versus 24.5 (SD = 3.0), mean difference = 7.8, 95% CI -0.3, 15.9, p = .06). However, groups were not randomised and only those who completed treatment were analysed, so estimates may be biased. 11 patients and five therapists were interviewed. Overall, both therapists and clients viewed online EMDR as safe and effective. Benefits mentioned by clients included feeling more in control and not having to travel. Clients' concerns related to lack of privacy and 'transition time/space' between therapy and their daily lives.Conclusion: Results suggest that online EMDR is an acceptable, safe and effective alternative to in-person EMDR for PTSD in this service.

This service evaluation assessed how online Eye Movement Desensitisation and Reprocessing (EMDR) compared to in-person EMDR in people with PTSD.Individuals receiving online EMDR had lower PTSD scores at the end of therapy, but the evidence for this was weak and as this was not a randomised trial we do not know whether this was due to the mode of therapy or other characteristics of clients receiving online therapy.Clients and therapists generally viewed online EMDR as being safe and effective, and supported the availability of online EMDR for PTSD.

Membrane procoagulation and N­terminomics/TAILS profiling in Montreal platelet syndrome kindred with VWF p.V1316M mutation.

BACKGROUND: The Montreal platelet syndrome kindred (MPS) with VWF p.V1316M mutation (2B-VWDMPS) is an extremely rare disorder. It has been associated with macrothrombocytopenia, spontaneous platelet clumping, mucocutaneous, and other bleeding, which can be largely prevented by von Willebrand factor (VWF) concentrate infusion. However, supplemental platelet transfusion has been required on occasion, particularly for severe gastrointestinal bleeds. This raised the question of whether a previously uncharacterized platelet dysfunction contributes to bleeding diathesis in 2B-VWDMPS patients. We have previously shown that membrane ballooning, a principal part of the platelet procoagulant membrane dynamics (PMD) after collagen stimulation, is driven by the influx of Na+ and Cl-, followed by the entry of water. METHODS: We study two members (mother and daughter) of the MPS kindred with severe bleeding phenotype and address this question by coupling quantitative platelet shotgun proteomics and validating biochemical assays, with the systematic analysis of platelet procoagulant membrane dynamics (PMD). Using N-terminomics/TAILS (terminal amine isotopic labeling of substrates), we compare changes in proteolysis between healthy and 2B-VWDMPS platelets. RESULTS: Here, we report in 2B-VWDMPS platelets, the loss of the transmembrane chloride channel-1 (CLIC1), and reduced chloride ion influx after collagen stimulation. This was associated with diminished membrane ballooning, phosphatidylserine externalization, and membrane thrombin formation, as well as a distinct phenotypic composition of platelets over fibrillar collagen. We also identify processing differences of VWF, fibronectin (FN1), and Crk-like protein (CRKL). 2B-VWDMPS platelets are shown to be basally activated, partially degranulated, and have marked loss of regulatory, cytoskeletal, and contractile proteins. CONCLUSIONS: This may account for structural disorganization, giant platelet formation, and a weakened hemostatic response.

The Montreal platelet syndrome (MPS) is a very rare genetic illness caused by a specific modification in a protein called von Willebrand factor (VWF). VWF circulates in the blood and works with platelets to stop blood from escaping when blood vessels are injured. People with MPS have a bleeding problem, as they have decreased circulating VWF activity and platelets that also don't function as expected. Here, we studied a mother and a daughter who live with this condition to better understand if there are other reasons behind the bleeding issues in this family. These participants had low levels of several other proteins, and their platelets did not gather as usual to arrest bleeding. They also did not undergo the usual changes in shape. These changes could contribute to the bleeding problems reported in this family.

Deep Ocular Phenotyping Across Primary Open-Angle Glaucoma Genetic Burden.

Importance: Better understanding of primary open-angle glaucoma (POAG) genetics could enable timely screening and promote individualized disease risk prognostication. Objective: To evaluate phenotypic features across genetic burden for POAG. Design, Setting, and Participants: This was a cross-sectional, population-based study conducted from 2006 to 2010. Included participants were individuals from the UK Biobank aged 40 to 69 years. Individuals with non-POAG forms of glaucoma were excluded from the analysis. Data were statistically analyzed from October 2022 to January 2023. Main Outcomes and Measures: POAG prevalence based on structural coding, self-reports, and glaucoma-related traits. Results: Among 407 667 participants (mean [SD] age, 56.3 [8.1] years; 219 183 majority sex [53.8%]) were 14 171 POAG cases. Area under receiver operating characteristic curve for POAG detection was 0.748 in a model including polygenic risk score (PRS), age, sex, and ancestry. POAG prevalence in the highest decile of PRS was 7.4% (3005 of 40 644) vs 1.3% (544 of 40 795) in lowest decile (P < .001). A 1-SD increase in PRS was associated with 1.74 times higher odds of POAG (95% CI, 1.71-1.77), a 0.61-mm Hg increase in corneal-compensated intraocular pressure (IOP; 95% CI, 0.59-0.64), a -0.09-mm Hg decrease in corneal hysteresis (95% CI, -0.10 to -0.08), a 0.08-mm Hg increase in corneal resistance factor (95% CI, 0.06-0.09), and a -0.08-diopter decrease in spherical equivalent (95% CI, -0.11 to -0.07; P < .001 for all). A 1-SD increase in PRS was associated with a thinning of the macula-region retinal nerve fiber layer (mRNFL) of 0.14 µm and macular ganglion cell complex (GCC) of 0.26 µm (P < .001 for both). In the subset of individuals with fundus photographs, a 1-SD increase in PRS was associated with 1.42 times higher odds of suspicious optic disc features (95% CI, 1.19-1.69) and a 0.013 increase in cup-disc ratio (CDR; 95% CI, 0.012-0.014; P < .001 for both). A total of 22 of 5193 fundus photographs (0.4%) in decile 10 had disc hemorrhages, and 27 of 5257 (0.5%) had suspicious optic disc features compared with 9 of 5158 (0.2%) and 10 of 5219 (0.2%), respectively, in decile 1 (P < .001 for both). CDR in decile 10 was 0.46 compared with 0.41 in decile 1 (P < .001). Conclusion and Relevance: Results suggest that PRS identified a group of individuals at substantially higher risk for POAG. Higher genetic risk was associated with more advanced disease, namely higher CDR and corneal-compensated IOP, thinner mRNFL, and thinner GCC. Associations with POAG PRS and corneal hysteresis and greater prevalence of disc hemorrhages were identified. These results suggest that genetic risk is an increasingly important parameter for risk stratification to consider in clinical practice.

Visual Functioning and Mortality of Age-Related Macular Degeneration Patients in a Colorado Cohort.

OBJECTIVE: To investigate the relationship between visual functioning as measured by the National Eye Institute 25-Item Visual Function Questionnaire (VFQ-25) and mortality in patients with various stages of age-related macular degeneration (AMD). DESIGN: Observational cohort study. PARTICIPANTS: Patients with AMD enrolled in the University of Colorado AMD Registry between July 9, 2014 and December 31, 2021 were included. METHODS: Age-related macular degeneration cases were classified into early AMD, intermediate AMD, geographic atrophy, neovascular AMD, or both advanced types of AMD (neovasuclar and geographic atrophy both present) using multimodal imaging and the Beckman and Classification of Atrophy Meetings criteria. Visual Function Questionnaire -25 composite and subscale scores at the time of study enrollment were calculated. Cox proportional hazards modeling was used to assess time to event for mortality utilizing univariate and multivariable models, which adjusted for all variables significantly associated with mortality. The measures of association were hazard ratios (HRs) and 95% confidence intervals (CIs). MAIN OUTCOME MEASURES: All-cause mortality statistics were obtained through a collaborative agreement with the Colorado Department of Public Health and Environment. Death rates through October 19, 2022 were compared by demographics and potential confounders. RESULTS: Analysis was completed on a cohort of 876 patients, of which 180 (20.6%) died during the follow-up period. Average follow-up time for this cohort was 52.5 (standard deviation: 26.6) months. In univariate analysis, composite VFQ-25 score and all subscale scores aside from ocular pain were significantly associated with time to mortality. Additionally, age, AMD category, marital status, history of smoking, and multiple chronic comorbid conditions were significantly associated with time to mortality. In multivariable analysis, for each 10-point increase in a patient's VFQ-25 scores for general health and driving, the risk of death decreased with HR of 0.85 (95% CI: 0.80, 0.91; P < 0.0001) and 0.92 (95% CI: 0.87, 0.97; P = 0.005), respectively. Composite and other subscale scores were not significantly associated with mortality after adjusting for confounding variables. CONCLUSIONS: This cohort of AMD patients had a 20% rate of death in the 52.5-month average follow-up time. Better general health and ability to drive, as measured by the VFQ-25, were each separately associated with significantly lower risk of death among individuals with AMD. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Vegan and vegetarian males and females have higher orthorexic traits than omnivores, and are motivated in their food choice by factors including ethics and weight control.

BACKGROUND: Evidence associating plant-based diets with the proposed 'obsessively healthy eating' eating disorder, orthorexia nervosa, has mostly focused on females. Diet motivations have seldom been assessed. AIM: To compare orthorexic tendencies between vegans/vegetarians and omnivores of both sexes, and reasons behind food choice with an English-validated Food Choice Questionnaire. METHODS: A cross-sectional survey of 444 males and females were recruited via social media, email, and Amazon MTurk; to investigate eating patterns, orthorexic tendencies using the ORTO-15 questionnaire, and eating motivations using the Food Choice Questionnaire. RESULTS: Over half of the participants were male (53.4%), younger adults (mean ± SD 37.2 ± 11.2 years), and mostly from the United States (89%). Vegan and vegetarian eating habits were reported by 15.8% of people. Vegans/vegetarians had significantly higher orthorexic tendencies than omnivores, and chose food significantly more often for Weight Control, Ethical Concern, Natural Content, and Mood reasons. People with greater orthorexic tendencies (ORTO-15 score<35) chose food significantly more often for Weight Control and Ethical Concern reasons than those with less orthorexic tendencies (ORTO-15 score 35+). CONCLUSION: This study's results are in line with the majority of the evidence that shows an association between vegan/vegetarian diets and orthorexic tendencies, but strengthens the evidence base by including more male participants. Additionally, this is the first study to use an English-validated motivation-based questionnaire that explored diet motivators in vegans/vegetarians compared to omnivories, and in those with orthorexic tendencies vs. those without orthorexic tendencies.

Evaluating the role of sexual antagonism in the evolution of sex chromosomes: new data from fish.

The recent increase in available molecular and genomic data for diverse taxa helps to shed new light on long-standing theories. Research into sex chromosome evolution has particularly benefited from a growing number of studies of fish, motivated by their highly diverse mechanisms of sex determination. Sexual antagonism is regularly cited as an influential force in sex chromosome emergence; however, this so far proves difficult to demonstrate. In this review, we highlight recent developments in the investigation of sexual antagonism in sex chromosome research in fish. We find strong emphasis placed on study-organism specific genomic features and patterns of recombination, rather than evidence for a comprehensive role of sexual antagonism. In this light, we discuss the alternative models of sex chromosome evolution. We conclude that fish represents a key resource for further research, provided attention is given to species-specific effects while simultaneously integrating comparative studies across taxa for a vital and comprehensive understanding of sex chromosome evolution and investigation of proposed models.

Messaging preferences for the role of pharmacists in pharmacy education recruitment material.

INTRODUCTION: Applications to pharmacy programs are declining worldwide. Previous research suggests that positioning of recruitment material according to prospective students' preferences may increase interest in the profession and entry-to-practice programs. The aim of this study was to determine messaging preferences for the role of the pharmacist. METHODS: This was a best-worst choice survey conducted at one institution in one country. Participants included prospective students, current pharmacy students, and others representing the general public. Thirteen statements (plus one control) describing the role of the pharmacist were extracted from pharmacy program websites. Survey participants completed the best-worst choice analysis, and a conditional logit model was used to estimate statement preference coefficients. RESULTS: A total of 150 complete survey responses were collected. The top ranked statement was, "Pharmacists are health care professionals who are experts in medicines" and the least ranked statement was the control statement, "Pharmacists are experts in dispensing medications and counting tablets." No differences were observed between the different groups of survey respondents. Other highly ranked statements spoke to the expertise of the pharmacist and promoted a well-defined role. Catchy statements, such as "Pharmacists are medicines superheroes," were not ranked highly. CONCLUSIONS: This study found that current and prospective pharmacy students preferred descriptive and explicit messages that align with pharmacists' professional identity for promotion of the pharmacist's role.

A systematic review of the barriers, enablers and strategies to embedding translational research within the public hospital system focusing on nursing and allied health professions.

AIM: This systematic review aims to investigate, identify, and compare evidence related to the barriers, enablers, and strategies to embedding translational research within a public hospital system focussed on nursing and allied health disciplines. METHODS: A systematic review looking at the international literature on the barriers, enablers and strategies in embedding translational research within a public health system addressing nursing and allied health professions. The study channelled the PRISMA reporting guidelines for systematic reviews and meta-analyses. Databases searched were Medline, Embase, Scopus and Pubmed from January 2011 to December 2021 (inclusive). A quality assessment was conducted of literature using the mixed methods appraisal tool 2011 version. RESULTS: Thirteen papers met the inclusion criteria. The studies included were from Australia, Saudi Arabia, China, Denmark and Canada. Occupational therapy and physiotherapy were the only two allied health disciplines identified in the search process. The review found considerable inter-relationships between the enablers, barriers, and strategies to embedding research translation in a public hospital setting. Three over-arching themes 'leadership, organisational culture and capabilities' were developed to capture the complexity of factors in embedding translational research. Key subthemes identified were education, knowledge, management, time, workplace culture and resources. All thirteen articles identified that a multifactorial approach is required to embed a research culture and translate research findings into clinical practice. CONCLUSIONS: The themes of leadership, organisational culture and capabilities are inherently intertwined and therefore successful strategies require a whole of health approach with organisational leadership driving the strategy, as changing organisational culture takes time and considerable investment. We recommend that public health organisations, senior executives and policy makers consider the findings of this review to provide evidence to initiate organisational changes to support and help create a research environment to drive research translation within the public sector.

Sexual selection and the evolution of condition-dependence: an experimental test at two resource levels.

Stronger condition-dependence in sexually selected traits is well-documented, but how this relationship is established remains unknown. Moreover, resource availability can shape responses to sexual selection, but resource effects on the relationship between sexual selection and condition-dependence are also unknown. In this study, we directly test the hypotheses that sexual selection drives the evolution of stronger-condition-dependence and that resource availability affects the outcome, by evolving fruit flies (Drosophila melanogaster) under relatively strong or weak sexual selection (through varied sex ratios) and at resource-poor or resource-rich adult diets. We then experimentally manipulated condition via developmental diet and assessed condition-dependence in adult morphology, behavior, and reproduction. We observed stronger condition-dependence in female size in male-biased populations and in female ovariole production in resource-limited populations. However, we found no evidence that male condition-dependence increased in response to sexual selection, or that responses depended on resource levels. These results offer no support for the hypotheses that sexual selection increases male condition-dependence or that sexual selection's influence on condition-dependence is influenced by resource availability. Our study is, to our knowledge, the first experimental test of these hypotheses. If the results we report are general, then sexual selection's influence on the evolution of condition-dependence may be less important than predicted.

Emerging technologies in the study of the virome.

Despite the growing interest in the microbiome in recent years, the study of the virome, the major part of which is made up of bacteriophages, is relatively underdeveloped compared with their bacterial counterparts. This is due in part to the lack of a universally conserved marker such as the 16S rRNA gene. For this reason, the development of metagenomic approaches was a major milestone in the study of the viruses in the microbiome or virome. However, it has become increasingly clear that these wet-lab methods have not yet been able to detect the full range of viruses present, and our understanding of the composition of the virome remains incomplete. In recent years, a range of new technologies has been developed to further our understanding. Direct RNA-Seq technologies bypass the need for cDNA synthesis, thus avoiding biases subjected to this step, which further expands our understanding of RNA viruses. The new generation of amplification methods could solve the low biomass issue relevant to most virome samples while reducing the error rate and biases caused by whole genome amplification. The application of long-read sequencing to virome samples can resolve the shortcomings of short-read sequencing in generating complete viral genomes and avoid the biases introduced by the assembly. Novel experimental methods developed to measure viruses' host range can help overcome the challenges of assigning hosts to many phages, specifically unculturable ones.

Information for children and young people about reporting suspected adverse drug reactions.

BACKGROUND: When children and young people (CYP) report their own suspected adverse drug reactions (ADRs), different patterns of drugs and symptoms are noted. A new guide to reporting suspected ADRs using the Medicines and Healthcare Products Regulatory Agency (MHRA) Yellow Card scheme was developed by CYP, paediatric clinical pharmacology, Yellow Card Centres and the MHRA. METHODS: An anonymous quality improvement project to assess the guide for CYP was undertaken (September 2020-February 2021). RESULTS: The survey was completed by 234 CYP age 13-18 years. Within respondents, 68/226 (30.1%) were using medicines, 209/225 (92.9%) had used medicines previously, and 211/225 (93.8%) had heard of side effects. 79/225 (35.1%) believed they had experienced a side effect, with some requiring hospitalisation. Only 8/221 (3.6%) respondents were aware of the MHRA Yellow Card scheme.Overall, 182/196 (92.9%) of CYP both understood the guide and felt more knowledgeable about how to report suspected side effects. CYP comfortable to report their own suspected ADR increased from 179/222 (80.6%) before reading guide, to 189/196 (96.4%) after reading the new CYP guide. In addition, 156/196 (79.6%) believed they would report a side effect from a medicine used in future. Over 360 free-text comments were also received, providing comments about what was good about the new guide and areas for improvement that could be made. CONCLUSION: The new guide for CYP to inform them about how to report a suspected ADR to the MHRA was well received and increased the knowledge, and confidence to report, in those who responded.

Genomics of altitude-associated wing shape in two tropical butterflies.

Understanding how organisms adapt to their local environment is central to evolution. With new whole-genome sequencing technologies and the explosion of data, deciphering the genomic basis of complex traits that are ecologically relevant is becoming increasingly feasible. Here, we studied the genomic basis of wing shape in two Neotropical butterflies that inhabit large geographical ranges. Heliconius butterflies at high elevations have been shown to generally have rounder wings than those in the lowlands. We reared over 1,100 butterflies from 71 broods of H. erato and H. melpomene in common-garden conditions and showed that wing aspect ratio, that is, elongatedness, is highly heritable in both species and that elevation-associated wing aspect ratio differences are maintained. Genome-wide associations with a published data set of 666 whole genomes from across a hybrid zone, uncovered a highly polygenic basis to wing aspect ratio variation in the wild. We identified several genes that have roles in wing morphogenesis or wing aspect ratio variation in Drosophila flies, making them promising candidates for future studies. There was little evidence for molecular parallelism in the two species, with only one shared candidate gene, nor for a role of the four known colour pattern loci, except for optix in H. erato. Thus, we present the first insights into the heritability and genomic basis of within-species wing aspect ratio in two Heliconius species, adding to a growing body of evidence that polygenic adaptation may underlie many ecologically relevant traits.

Investigating Bacteriophages Targeting the Opportunistic Pathogen Acinetobacter baumannii.

The multi-drug resistance of the opportunistic pathogen Acinetobacter baumannii is of growing concern, with many clinical isolates proving to be resistant to last resort as well as front line antibiotic treatments. The use of bacteriophages is an attractive alternative to controlling and treating this emerging nosocomial pathogen. In this study, we have investigated bacteriophages collected from hospital wastewater in Thailand and we have explored their activity against clinical isolates of A. baumannii. Bacteriophage vB_AbaM_PhT2 showed 28% host range against 150 multidrug resistant (MDR) isolates and whole genome sequencing did not detect any known virulence factors or antibiotic resistance genes. Purified vB_AbaM_PhT2 samples had endotoxin levels below those recommended for preclinical trials and were not shown to be directly cytotoxic to human cell lines in vitro. The treatment of human brain and bladder cell lines grown in the presence of A. baumannii with this bacteriophage released significantly less lactate dehydrogenase compared to samples with no bacteriophage treatment, indicating that vB_AbaM_PhT2 can protect from A. baumannii induced cellular damage. Our results have also indicated that there is synergy between this bacteriophage and the end line antibiotic colistin. We therefore propose bacteriophage vB_AbaM_PhT2 as a good candidate for future research and for its potential development into a surface antimicrobial for use in hospitals.

Intraoperative storage of saphenous vein grafts in coronary artery bypass grafting.

Background: Saline is not biocompatible with saphenous vein grafts and does not protect against ischemia reperfusion injury. We compared normal heparinized saline with DuraGraft, a new graft-storage solution, in in-vitro and ex-vivo assays to evaluate the effects on cells and vascular graft tissue.Methods: Human saphenous vein (HSV) segments and isolated pig mammary veins (PMVs) were flushed and submerged in heparinized DuraGraft or heparinized saline for prespecified times. Following exposure, HSV segments were evaluated for viability and tissue morphology, and PMVs underwent histological assessments, to evaluate vein morphology and effects on the vascular endothelium. The performance of saline versus DuraGraft was compared in an ISO-compliant biocompatibility assay for cytotoxicity.Results: Loss of HSV graft-cell viability was observed as early as 15 minutes post-exposure to saline whereas viability was maintained up to 5 hours' exposure to DuraGraft. Histological analyses performed with PMVs demonstrated endothelial damage in PMVs stored in saline. Cytotoxicity assays demonstrated that saline-induced microscopically visible cell damage occurred within 60 minutes. DuraGraft-treated cells did not show evidence of damage or reactivity.Conclusions: Normal saline caused damage to vascular endothelium, loss of graft cell viability, and mediated cell damage; no evidence of damage or reactivity was observed in DuraGraft-exposed cells.