Diversification of the hexaploid (bread) wheat genetic pool using wild genetic resources relies on effective meiotic recombination (crossover) between wheat chromosomes and their counterparts from related species (homoeologues). However, crossover between homoeologues is normally suppressed by two major genes, ZIP4-5B (Ph1) and MSH7-3D (Ph2). We investigated the effect of introducing zip4-5B and/or msh7-3D mutations into interspecific hybrids derived from crosses between wheat and Aegilops variabilis. Single and double mutants were exploited in Chinese Spring (CS) and Cadenza (Cad) genetic backgrounds, as well as in a CS/Cad recombinant background. Meiotic cells at metaphase I were scored for univalents, bivalents, and multivalents, from which chiasma numbers were deduced. We demonstrated a non-cumulative effect of simultaneous zip4-5B and msh7-3D mutations on homoeologous recombination, as homoeologous crossovers reached a maximum when ZIP4-5B alone was mutated. We also showed that hybrids carrying both the zip4-5B and msh7-3D mutations in the same genetic background exhibited a higher recombination rate compared to a double mutant in the CS/Cad recombinant background. The progression of meiosis was also monitored in the various interspecific hybrids mutants, revealing clear disruptions. Thus, our study provides key insights for optimizing the introgression of beneficial alleles from wild relatives into elite wheat germplasm; first by demonstrating the efficiency of ZIP4-5B and MSH7-3D mutations independently and in combination and second by elucidating the influence of the genetic background in which these mutations are present in an interspecific hybrid context.

Introduction Adolescent mental health problems represent a significant global health issue, particularly in low- and middle-income countries, such as the Republic of North Macedonia and the Republic of Moldova. Effective and scalable interventions are urgently needed to address these challenges.Methods and analysis This protocol outlines a multicountry cluster randomised factorial trial, implemented according to the multiphase optimisation strategy (Phase 2), which evaluates the effectiveness and costs of three add-on components for the Parenting for Lifelong Health for Parents and Teens programme: adolescent mental health tools based on UNICEFs Helping Adolescents Thrive comics, adolescent peer support based on UNICEFs ‘I Support My Friends’ intervention and engagement booster designed to enhance attendance and programme completion through incentives. The study will recruit 720 families and involve 64 clusters in North Macedonia and Moldova. Primary outcomes will include adolescent internalising problems and social support, family functioning and attendance during the programme. Secondary outcomes will assess broader aspects of mental health among caregivers and adolescents, as well as implementation and cost outcomes. Data will be collected at baseline and postintervention, approximately, 8 weeks later. Statistical analyses will include regression models to assess the main and interaction effects of the intervention components and cost analyses.Ethics and dissemination The study received ethical approval from the University of Klagenfurt in Austria (approval number: 2023–013), the Medical Faculty at St. Cyril and Methodius University in North Macedonia (approval number: 03-2144/4) and the National Committee of Ethical Expertise for Clinical Trials in Moldova (approval number: 1476). The results will be disseminated through peer-reviewed journals, conferences, webinars in multiple languages, regional forums, stakeholder meetings with policymakers and practitioners, public communication through media engagement and open access platforms, including data sharing and early release of findings.Trial registration details Trial registration: NCT06562244; Project page: https://www.flourish-study.org/about.html

Transition from primary to secondary school is an important life event for young people that may have impacts on mental health. Objective and subjective measures of the school environment may be associated with mental health outcomes post-transition. Pre-transition (year 6, aged 10–11) survey data from young people in Wales, UK, were linked to post-transition (year 7, aged 11–12) survey data (n = 506) and combined with an objective value-added measure of school meaningfulness created from administrative data. Multi-level models were run, adjusting for pre-transition mental health difficulties, to investigate the relationship between individual and school-level variables, including self-reported perceptions of school connectedness and school meaningfulness, and mental health difficulties and mental wellbeing outcomes post-transition. Pre-transition mental health difficulties were consistently significantly associated with post-transition mental health difficulties. Higher family affluence was significantly associated with higher mental wellbeing and lower difficulties. School connectedness items also showed evidence of significant association with mental health difficulties and wellbeing outcomes post-transition. School meaningfulness was only significantly associated with post-transition mental wellbeing. Individual- and school-level factors offer opportunities for targeting interventions to support young people’s mental health and wellbeing across the school transition period.

Schools are increasingly positioned as key settings for promoting health behaviours and well‐being. Curriculum for Wales (CfW) represents major national reform of the Welsh education system, placing unprecedented focus on health and well‐being for learners in compulsory education (aged 3–16). Qualitative case studies across four schools in Wales explored staff perceptions of, and preparation for, roll out of CfW from September 2022. Interviews ( n = 13) were conducted with a range of staff, including senior management, health and well‐being leads and newly qualified teachers. Thematic analysis was used to summarise data into five overarching themes: ‘reframing the system’; ‘operationalising the reform’; identifying ‘expectations for success’; ‘national level barriers and facilitators’; and ‘community and school‐level barriers and facilitators’. Findings highlighted ‘traditional’ pressures on schools to maintain high academic performance, which were at odds with a ‘holistic’ view of life‐long pupil development and health and well‐being encouraged by the reforms. Where ‘top‐down’ governance and professional culture were perceived to be leading factors influencing national implementation, support for partnership working was perceived to be a critical facilitator of delivery at the school level. Results suggest a need to support health and well‐being practice of schools across multiple levels of the system, to develop structures that enable professional development and effective partnership working, and equip schools with the appropriate resources to respond to a changing environment.

Dementia is a complex health condition that poses challenges not only to people living with dementia (PLWD) but to their families, the health system and society as a whole. Even though there is still no cure for dementia, different interventions are showing substantial contribution. mHealth-based assistive technology has shown the potential to provide efficient healthcare for PLWD and their caregivers in cognitive training, health and safety monitoring, educational support, and socialization. Also, Care Navigation Systems offers person-centered, strengths-based, and continuous support to PLWD and their caregivers across the illness trajectory and different settings through collaborative problem-solving and coaching. The IMPACT project will propose innovative solutions for dementia using a collaborative and multidisciplinary approach. For that reason, one of its components aims to adapt an existing intervention to improve the quality of life for PLWD and wellbeing of their caregivers to develop a context-fit intervention in Peru. To adapt an existing intervention from a High-Income Country to the Peruvian context: The original intervention, The Care Ecosystem, is a supportive care navigation system delivered over the phone and the internet by care team navigators who respond to PLWD and caregivers’ immediate needs, provide personalized support and education using care plan protocols. Phase 1: Will include the revision of the care protocols used by the original intervention to contrast their relevance and cultural fit with the experiences and needs of PLWD and ther caregivers from 4 regions of Peru (Lima, Tumbes, Iquitos, and Huancayo). This process will include a co-design process with dementia experts, health providers and target population. Phase 2: Conduct a feasibility trial of the adapted intervention on 120 PLWD/caregiver dyas (60 control group, 60 intervention group) during a period of 9 months. We expect to identify core change mechanisims of the Care Ecosystem program and develop an adapted intervention that can be cosidered feasible to implement within the Peruvian context. The adaptation of the intervention will offer insights about the convenience of working with evidence- based interventions and the opportunities that can arise when they are carefully tailored to different context, norms and existing resources.

Peru does not have official prevalence data of dementia, however, particular studies indicate that in urban areas 6.85% of the population over 65 years of age has it. Countries such as Peru have significant drivers of the condition such as low socio-economic (monetary poverty 27.5%) and educational levels (21.9% of the population has only primary education). In order to prepare the health system and society in general, it is necessary to start multisectoral studies to understand the complexity of the challenge ahead. The IMPACT project aims to contribute to this. Mixed methods approach. Semi-structured interviews with different stakeholders as well as secondary data review to cover 11 themes from the health system (policy environment, financing, infrastructure, service delivery in prevention and management issues, etc.) in three levels (macro, meso and micro) nnd in four different areas of Peru The presentation still does not show results, as it is still ongoing. However, we are sharing some of the insights and learnings we have gained so far. Some of these are the following: limited and heterogeneous response due to the highly fragmented system, lack of political support, first level of care not designed or prepared to deal with dementia cases, reduced amount of specialists, adequate training for health providers attending this group, no guidelines for medical practices and limited research about its characteristics and needs. Also, age stereotypes and lack of awareness about dementia as a medical condition persist in all levels of the health system and society, negatively affecting the effectiveness of its response to their needs These are some preliminary Conclusions: more research is needed, to address stereotypes, increase training for health providers, use technology to facilitate access to services, create models of effective implementation to generate impact on urgent issues and inclusion of preventive and long-term care approaches

Schools are important settings for intervention to improve mental health. Much school mental health research has focused on schools as an avenue to reach large numbers of young people with new interventions, added on top of what schools currently do. However, research is increasingly focused on changing the school system itself to improve mental health, with a growing emphasis on improving school climate. This article begins by exploring wider debates on the benefits and harms of school-based interventions, before focusing on school climate as a target for intervention. It reviews evidence from intervention studies and systematic reviews to understand effectiveness, how interventions reduce or amplify inequalities, and real-world impacts. School climate research has grown rapidly since the turn of the century. It remains difficult to define. Definitions vary in whether they include focus on physical environments and educational instruction. However, they converge on focus on positive relationships among a school community and safety. Several large trials of interventions to improve mental health, by improving school climate, have been conducted in a range of international contexts. While many have not been effective, recent trials provide evidence that interventions can improve school climate and mental health, as well as a range of risk behaviours. Few studies examine effects on inequalities in mental health, with tentative evidence that school climate interventions have been more effective for some groups than others (e.g., bigger effects for boys than for girls). Evidence on scalability and sustainability indicates that typically small effects from trials may not fully translate into real-world change. There is growing evidence that improving school climate interventions can improve child and adolescent mental health. More research is needed on how such interventions can contribute to reducing inequalities. Further work is needed to understand how effects translate into real-world public health impact.

Reproductive, male-enriched small RNAs are present in flowering plants and animals, yet their role in plants remains underexplored. We generated dicer-like 5 (dcl5) mutants in durum wheat (Triticum turgidum ssp. durum 2n = 4× = 28; AABB), revealing temperature-sensitive genic male sterility. Loss of DCL5 depleted premeiotic and meiotic 24-nt phasiRNA production, correlating with sterility under standard growth conditions and partial fertility recovery at higher temperatures. A single functional DCL5 allele restored complete fertility, presenting a promising alternative to current methods for hybrid production. We demonstrate that premeiotic 24-nt phasiRNA biogenesis is independent of miRNA-mediated cleavage and driven by a conserved motif initiating DCL5 activity. In the dcl5 mutant developing under sterility-inducing conditions, developmental defects are observed during pollen maturation, rather than at peak 24-nt phasiRNA accumulation in premeiotic and meiotic anthers. Although no visible morphological abnormalities were apparent during early development, single-cell RNA sequencing revealed that dcl5 mutant cells exhibit transcriptional profiles distinct from those of wild-type cells, when premeiotic 24-nt phasiRNAs are accumulating at the early developmental stage. Finally, the coexpression of Argonaute (AGO1b, AGO4a, and AGO6) homeologs in 24-nt phasiRNA-producing cells identifies candidate effectors and suggests a role for 24-nt phasiRNAs in transcriptional gene silencing.

Introduction Young people (YP) whose parents have depression are at elevated risk for developing depression themselves and could benefit from preventive interventions. However, when parents are in a depressive episode, this reduces the effects of psychological interventions for depression in YP. Moreover, parental depression is often managed suboptimally in usual care. There is, therefore, a case for identifying and optimising parental depression treatment to enhance the effectiveness of psychological preventive interventions for depression in YP.Methods and analysis This is a randomised controlled trial (Skills for adolescent WELLbeing) to determine the effectiveness of a cognitive behavioural therapy (CBT) intervention compared with usual care in increasing the time to a major depressive episode in YP by 9-month follow-up (primary outcome). The intervention offers a 12-week treatment-optimisation phase for parents depressed at study entry, followed by randomisation of the young person to a small group manualised online CBT programme facilitated by a therapist. YP allocated to the intervention will receive eight weekly sessions plus three monthly continuation sessions. Secondary outcomes include the number of depression-free weeks, mental health symptoms and functioning. Mechanisms of intervention action will be assessed with mediation analysis of quantitative data and thematic analysis of qualitative interviews. Participants (parents/carers with depression and their children aged 13–19 years) will be identified through existing cohorts of adults with depression, from primary care through health boards in Wales and England, UK, schools and advertising including via social media.Ethics and dissemination The trial has received ethical approval from Wales NHS Research Ethics Committee (REC) 5, the Health Research Authority and Health and Care Research Wales (IRAS 305331; REC 22/WA/0254). This manuscript is based on V.5.7 of the protocol (17 January 2025). Findings will be disseminated in peer-reviewed journals and conferences. Reports and social media messages will be used to disseminate findings to the wider public.Trial registration number ISRCTN13924193 (date registered: 15 March 2023).

Logic models are valuable tools when evaluating complex interventions in public health. They can improve the understanding of how an intervention works and interacts with its system, and facilitate clear communication regarding the intervention with stakeholders. There are different approaches to developing logic models. However, experiences with logic model development in practice, and the advantages or challenges associated with different approaches are rarely reported. This study describes and reflects on the staged development process of a logic model for the municipal public health intervention Präventionskette Freiham in Munich, Germany. Specifically, we aim to identify advantages and challenges associated with this process, and deduce lessons learnt for staged logic model development and logic model development in general. For the staged logic model development process, a first draft of the logic model was developed at the start of the evaluation. We then defined a priori milestones at which the model was to be revised. It was revisited and updated: (i) after the process evaluation, (ii) after a workshop with stakeholders, and (iii) at the end of preparations for long-term outcome evaluation. We discussed the advantages and challenges associated with the staged development process in a workshop within the research team, and obtained feedback on the usefulness of the logic model during a workshop with municipal stakeholders. The logic model changed in multiple aspects during the different stages of development, mostly due to evidence obtained during the evaluation and as a result of feedback from discussions within the research team and with stakeholders. In the workshop with the research team, we found the staged process to be useful for facilitating reflection, for increasing plannability of logic model development, for integrating multiple perspectives and for increasing the validity of the logic model. Challenges were the need for rigorous documentation and flexibility in the process, as well as the management of resources. In the stakeholder workshop on the usefulness of the logic model, participants stated that the graphical visualization made it easier to handle complexity, and wished for the logic model to be re-used for future interventions. Developing a logic model in a staged process over the course of the evaluation of an intervention is a useful approach for stimulating reflection and obtaining a more realistic depiction of the intervention.

In 2021, the Welsh Government introduced new statutory guidance for schools titled ‘Framework Guidance on Embedding a Whole School Approach to Emotional and Mental Wellbeing’. This document outlined new responsibilities for educational settings to work towards incorporating a whole school approach, with regard to the Framework in action planning, service delivery and policy in relation to the mental and emotional wellbeing of learners and staff. While there is growing evidence to suggest that whole school approaches can be beneficial to social and emotional wellbeing for pupils, evidence on effective implementation is limited. This paper reports on findings from qualitative group interviews with staff in schools in Wales, conducted as part of a wider, mixed-methods evaluation of the Framework. It focuses on factors in the school context which impacted initial implementation. A number of school level factors were identified as barriers to implementation and staff engagement with the Framework. School staff reported higher levels of pupil mental health challenges stemming from the COVID-19 pandemic and an absence of capacity in in-house and external support services to address this. Poor staff wellbeing and significant workload pressures were also reported, driven in part by concurrent implementation of the new Curriculum For Wales. This led staff to feel ill-prepared for the more complex issues being faced, exacerbated by a lack of access to relevant training to be able to support pupil and colleague mental health. This paper concludes with recommendations for policy-makers to support Framework implementation.

BACKGROUND:EDs can address modifiable risks of patients attending due to violence. Hospital-based violence intervention programmes (HVIPs) can reduce patients' exposure to violence but can place additional burdens on staff. We explored practitioners' views on two nurse-led HVIPs' design and delivery, response to patient need, engagement with ED health professionals, adaptation to local context and analysed documents relevant to these objectives. METHODS:This was a qualitative process evaluation, from January to September 2023, of two nurse-led HVIPs implemented in a major trauma centre and a large urban hospital in the UK. Interview participants (N=49) were involved with the commission and implementation of the HVIPs, or worked within the broader violence-prevention ecology. We gathered perspectives on intervention implementation and undertook documentary analysis on local and national policies, and guidance relating to HVIPs development, implementation and delivery (N=46). Documentary data were subject to thematic and content analyses, interview data to thematic analysis. RESULTS:HVIPs were developed in response to a perceived under-provision of services for patients attending EDs due to violence. The HVIP nurses had access to clinical records facilitating the identification of eligible patients. They provided patient-centred care, addressing needs through referrals into health and community-based services. Over 60% of eligible patients engaged. The nurses were seen as credible champions working towards a minimally burdensome service that supported and trained ED staff. Embedding HVIPs into usual care took time and was limited by the perceived short-term nature of the intervention. CONCLUSION:The implementation of nurse-led HVIPs enables access to clinical records, facilitating patient engagement, and can provide an additional service aligned to usual emergency care, supporting both patients and ED staff. PRE-REGISTRATION:The protocol was pre-registered (ISRCTN 15286575; March 13, 2023) and published before data collection was complete.

Background:Emotional problems among adolescents have increased substantially in recent years, and there is evidence that schoolwork pressures have also increased globally. We examine trends in perceived schoolwork pressure and emotional problems in Wales between 2002 and 2021, and associations between the two over this period. Methods:Repeat cross-sectional data were used from surveys conducted in secondary schools in Wales. Participants were 11-16-year-olds (n = 318,554). Measures included self-reported perceived schoolwork pressure and emotional problems (HBSC-SCL). Results:The percentage of students reporting a lot of perceived schoolwork pressure increased from 21% in 2002, to 24% in 2004. Rates then declined until 2009, dropping to 13%, before increasing to nearly 26% by 2021. Students reporting the most pressure were females in older school years, with up to 57% of females in Year 11 reporting a lot of perceived pressure in 2021. Emotional problems followed a similar trend, decreasing between 2002 and 2009, and then increasing between 2009 and 2021. Between 2009 and 2019, estimates of the cohort difference in emotional problems reduced from 2.23 (95% CI = 2.12, 2.34) to 1.64 (95% CI = 1.54, 1.75) when adjusting for changes in schoolwork pressure. This is consistent with the hypothesis that schoolwork pressure may be driving some of the increase in emotional problems over time. Conclusions:Our findings showed a decline in perceived school pressure until 2009, followed by a rise until 2021. Increases were particularly apparent among female adolescents, mirroring trends in emotional problems. Although a range of competing causal explanations cannot be ruled out, overall increases in schoolwork pressure from the late 2000s may have contributed to the rise in adolescent emotional problems over this period.

Girls’ physical activity levels decline to a greater extent than boys as they enter adolescence. Role model interventions offer a potential solution to combat this public health issue. This study reports findings of a feasibility study of the CHARMING (CHoosing Active Role Models to INspire Girls) programme, a 6-week after-school primary school-based, community linked, role-model intervention. Between January 2021 and August 2022, a feasibility cluster randomised controlled trial (cRCT), with process and health economic evaluations was conducted in South Wales. Secondary schools were recruited, along with their adjoining primary schools to recruit Year 5 girls (aged 9–10 years). Role models were recruited from the surrounding school community (community role models) and from each secondary school (peer role models). A survey of self-reported outcome measures and accelerometers were administered at baseline and at 12 months. Following baseline, six primary schools were randomly allocated to intervention or control (usual practice) on a 2:1 basis. Post-intervention delivery, observations (n = 30), focus groups (n = 13) and interviews (n = 22) were conducted to explore study and intervention acceptability, feasibility and fidelity. Five pre-specified progression criteria included: implementation, attendance rates, and acceptability of the intervention, as well as completion of the primary outcome, including levels of completeness. One hundred and fifty-six girls from six primary schools (four intervention and two control) were eligible to take part. Of these, 96 (62

Schools are an important setting for interventions to improve mental health. There is growing evidence that school climate – sometimes expressed as the perceptions that children have about the relationships, safety, values, and beliefs within their school – can impact child mental health. Poor child mental health is associated with feelings of distress as well deficits in functioning. However, while most studies have focused on school climate, climate at lower levels of nesting, including year group, may be important. Cross-sectional data on emotional and behavioural difficulties from 32,606 children in primary schools in Wales (ages 7–11, year groups 3–6) were collected via a school survey, delivered online and within the classroom environment to all children who consented, and analysed using multilevel modelling. Models were then extended to consider how aggregated measures of year group and school climate are associated with mental health outcomes. The unadjusted variance partition coefficients (VPCs) indicated that 2.8

Dementia is a global health priority with significant challenges due to its complex nature and increasing prevalence. Health systems worldwide struggle to address chronic conditions like dementia, often providing fragmented care. However, information about how health systems respond to the needs of people with dementia (PWD) and their carers, and the quality of care provided, is scarce in low- and middle- income countries This study aims to understand the response of the Peruvian health system to PWD and their carers as well as to explore the experiences of PWD of receiving their diagnosis, management and quality of care for this condition. Additionally, the study will explore the willingness of the health system and stakeholders to adopt new tools for the diagnosis, management and quality of care of dementia. This study is part of a research programme called “IMPACT Salud: Innovations using Mhealth for PWD and Co-morbidities”, aimed at strengthening health systems to provide care for PWD and their carers. The study has a descriptive, cross-sectional design that uses mixed methods methodology and consists of two sub-studies, a health system assessment and an exploration of the patient journey. The first sub-study employs a health system assessment methodology suitable for low- and middle-income countries, conducting 160 structured interviews with 12 different stakeholder types across three levels of the health system (micro, meso, and macro) in four Peruvian regions, each with distinct geographical and urbanization profile. The second sub-study, utilizes a patient journey methodology, which involves conducting 40 in-depth interviews with PWD, carers, and healthcare workers from the same four regions. The insights into the PWD patient and caregiver experience within the health system from the interviews will be used to produce a patient journey map. The analysis will be guided by the High-Quality Health System Framework and the findings from the health system assessment and patient journey will be structured using the domains included in the framework through the lens of quality of services. Data collection began in March 2024, aiming to finish by late July 2024. As of end of April 2024, 59 interviews from the health system assessment have been conducted in three regions. This study will provide a national, multi-level insight into the current operation of the Peruvian health system including an analysis of the quality of services provide, with regards dementia diagnosis, management and care; from the perspectives of system stakeholders, patients and their carers.

BACKGROUND:Hypertension worsens outcomes in SARS-CoV-2 patients. Sartans, a type of antihypertensive angiotensin receptor blocker-(ARB), reduce COVID-19 morbidity and mortality by targeting angiotensin-converting enzyme-2 (ACE2). This study aimed to evaluate the antiviral and antihypertensive effects of nirmatrelvir, commercial sartans (candesartan, losartan, and losartan carboxylic (Exp3174)), and newly synthesized sartans (benzimidazole-N-biphenyl carboxyl (ACC519C) and benzimidazole-N-biphenyl tetrazole (ACC519T)), compared to nirmatrelvir, the antiviral component of Paxlovid.RESEARCH DESIGN AND METHODS:Surface plasmon resonance (SPR) and enzymatic studies assessed drug effects on ACE2. Antiviral abilities were tested with SARS-CoV-2-infected Vero E6 cells, and antihypertensive effects were evaluated using angiotensin II-contracted rabbit iliac arteries.RESULTS:Benzimidazole-based candesartan and ACC519C showed antiviral activity comparable to nirmatrelvir (95% inhibition). Imidazole-based losartan, Exp3174, and ACC519T were less potent (75%-80% and 50%, respectively), with Exp3174 being the least effective. SPR analysis indicated high sartans-ACE2 binding affinity. Candesartan and nirmatrelvir combined had greater inhibitory and cytopathic effects (3.96%) than individually (6.10% and 5.08%). ACE2 enzymatic assays showed varying effects of novel sartans on ACE2. ACC519T significantly reduced angiotensin II-mediated contraction, unlike nirmatrelvir and ACC519T(2).CONCLUSION:This study reports the discovery of a new class of benzimidazole-based sartans that significantly inhibit SARS-CoV-2, likely due to their interaction with ACE2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, and respiratory syncytial virus (RSV) are significant global health threats. The need for low-cost, easily synthesized oral drugs for rapid deployment during outbreaks is crucial. Broad-spectrum therapeutics, or pan-antivirals, are designed to target multiple viral pathogens simultaneously by focusing on shared molecular features, such as common metal cofactors or conserved residues in viral catalytic domains. This study introduces a new generation of potent sartans, known as bisartans, engineered in our laboratories with negative charges from carboxylate or tetrazolate groups. These anionic tetrazoles interact strongly with cationic arginine residues or metal cations (e.g., Zn2+) within viral and host target sites, including the SARS-CoV-2 ACE2 receptor, influenza H1N1 neuraminidases, and the RSV fusion protein. Using virtual ligand docking and molecular dynamics, we investigated how bisartans and their analogs bind to these viral receptors, potentially blocking infection through a pan-antiviral mechanism. Bisartan, ACC519TT, demonstrated stable and high-affinity docking to key catalytic domains of the SARS-CoV-2 NSP3, H1N1 neuraminidase, and RSV fusion protein, outperforming FDA-approved drugs like Paxlovid and oseltamivir. It also showed strong binding to the arginine-rich furin cleavage sites S1/S2 and S2′, suggesting interference with SARS-CoV-2’s spike protein cleavage. The results highlight the potential of tetrazole-based bisartans as promising candidates for developing broad-spectrum antiviral therapies.

AbstractBackgroundAdolescence is a period of profound developmental change during which the prevalence of mental health problems starts to increase. It also typically coincides with a school transition. Understanding mental health trajectories through school transition is important to inform interventions to support young people's mental health during this period.MethodsIn a longitudinal study with three assessment points spaced six months apart spanning the transition from primary (T1 = end of primary school [Year 6]) to secondary school (T2 = beginning of the first year secondary school [Year 7]; T3 = end of first year of secondary school [Year 7]) we carried out a latent class growth analysis of symptoms of common mental health problems. Young people (mean age at baseline of 11.2 years, standard deviation 0.29; 46.8% female; 53.2% male) from South East England (n = 1861) were included. We modelled emotional problems, conduct problems, hyperactivity and peer problems in parallel over the transition period. Individual‐level variables: socioeconomic status (SES), special educational need(s) (SEN), gender, negative life events (NLEs) and being worried about transition were tested as predictors of trajectory class membership using multinomial logistic regression.ResultsA model with four trajectory classes provided the best fit to the data: ‘persistently elevated’ mental health problems, ‘emotional and peer problems’, ‘hyperactivity and conduct problems’ and ‘persistently low’ mental health problems. Class membership was differentially predicted by the individual‐level variables.ConclusionsYoung people from low SES backgrounds, those with SEN and those who have experienced two or more NLEs are more likely to exhibit trajectories with elevated mental health difficulties through the transition to secondary school. Young people who were worried about transition were more likely to belong to a trajectory class characterised by elevated emotional problems.