In-patient evolution of a high-persister Escherichia coli strain with reduced in vivo antibiotic susceptibility.

Gram-negative bacterial bloodstream infections (GNB-BSI) are common and frequently lethal. Despite appropriate antibiotic treatment, relapse of GNB-BSI with the same bacterial strain is common and associated with poor clinical outcomes and high healthcare costs. The role of persister cells, which are sub-populations of bacteria that survive for prolonged periods in the presence of bactericidal antibiotics, in relapse of GNB-BSI is unclear. Using a cohort of patients with relapsed GNB-BSI, we aimed to determine how the pathogen evolves within the patient between the initial and subsequent episodes of GNB-BSI and how these changes impact persistence. Using Escherichia coli clinical bloodstream isolate pairs (initial and relapse isolates) from patients with relapsed GNB-BSI, we found that 4/11 (36%) of the relapse isolates displayed a significant increase in persisters cells relative to the initial bloodstream infection isolate. In the relapsed E. coli strain with the greatest increase in persisters (100-fold relative to initial isolate), we determined that the increase was due to a loss-of-function mutation in the ptsI gene encoding Enzyme I of the phosphoenolpyruvate phosphotransferase system. The ptsI mutant was equally virulent in a murine bacteremia infection model but exhibited 10-fold increased survival to antibiotic treatment. This work addresses the controversy regarding the clinical relevance of persister formation by providing compelling data that not only do high-persister mutations arise during bloodstream infection in humans but also that these mutants display increased survival to antibiotic challenge in vivo.

Ultrasound-mediated antibiotic delivery to in vivo biofilm infections: A Review.

Bacterial biofilms are a significant concern in various medical contexts due to their resilience to our immune system as well as antibiotic therapy. Biofilms often require surgical removal and frequently lead to recurrent or chronic infections. Therefore, there is an urgent need for improved strategies to treat biofilm infections. Ultrasound-mediated drug delivery is a technique that combines ultrasound application, often with the administration of acoustically-active agents, to enhance drug delivery to specific target tissues or cells within the body. This method involves using ultrasound waves to assist in the transportation or activation of medications, improving their penetration, distribution, and efficacy at the desired site. The advantages of ultrasound-mediated drug delivery include targeted and localized delivery, reduced systemic side effects, and improved efficacy of the drug at lower doses. This review scrutinizes recent advances in the application of ultrasound-mediated drug delivery for treating biofilm infections, focusing on in vivo studies. We examine the strengths and limitations of this technology in the context of wound infections, device-associated infections, lung infections and abscesses, and discuss current gaps in knowledge and clinical translation considerations.

Fibrin(ogen) engagement of S. aureus promotes the host antimicrobial response and suppression of microbe dissemination following peritoneal infection.

The blood-clotting protein fibrin(ogen) plays a critical role in host defense against invading pathogens, particularly against peritoneal infection by the Gram-positive microbe Staphylococcus aureus. Here, we tested the hypothesis that direct binding between fibrin(ogen) and S. aureus is a component of the primary host antimicrobial response mechanism and prevention of secondary microbe dissemination from the peritoneal cavity. To establish a model system, we showed that fibrinogen isolated from FibγΔ5 mice, which express a mutant form lacking the final 5 amino acids of the fibrinogen γ chain (termed fibrinogenγΔ5), did not support S. aureus adherence when immobilized and clumping when in suspension. In contrast, purified wildtype fibrinogen supported robust adhesion and clumping that was largely dependent on S. aureus expression of the receptor clumping factor A (ClfA). Following peritoneal infection with S. aureus USA300, FibγΔ5 mice displayed worse survival compared to WT mice coupled to reduced bacterial killing within the peritoneal cavity and increased dissemination of the microbes into circulation and distant organs. The failure of acute bacterial killing, but not enhanced dissemination, was partially recapitulated by mice infected with S. aureus USA300 lacking ClfA. Fibrin polymer formation and coagulation transglutaminase Factor XIII each contributed to killing of the microbes within the peritoneal cavity, but only elimination of polymer formation enhanced systemic dissemination. Host macrophage depletion or selective elimination of the fibrin(ogen) ß2-integrin binding motif both compromised local bacterial killing and enhanced S. aureus systemic dissemination, suggesting fibrin polymer formation in and of itself was not sufficient to retain S. aureus within the peritoneal cavity. Collectively, these findings suggest that following peritoneal infection, the binding of S. aureus to stabilized fibrin matrices promotes a local, macrophage-mediated antimicrobial response essential for prevention of microbe dissemination and downstream host mortality.

Attitudes toward and experiences of clinical and non-clinical services among individuals who self-harm or attempt suicide: a systematic review.

The prevalence of self-harm has increased substantially in recent decades. Despite the development of guidelines for better management and prevention of self-harm, service users report that quality of care remains variable. A previous systematic review of research published to June 2006 documented largely negative experiences of clinical services among patients who self-harm. This systematic review summarized the literature published since then to July 2022 to examine contemporary attitudes toward and experience of clinical and non-clinical services among individuals who self-harm and their relatives. We systematically searched for literature using seven databases. Quality of studies was assessed using the Mixed-Methods Appraisal Tool and findings were summarized using a narrative synthesis. We identified 29 studies that met our inclusion criteria, all of which were from high- or middle-income countries and were generally of high methodological quality. Our narrative synthesis identified negative attitudes toward clinical management and organizational barriers across services. Generally, more positive attitudes were found toward non-clinical services providing therapeutic contact, such as voluntary sector organizations and social services, than clinical services, such as emergency departments and inpatient units. Views suggested that negative experiences of service provision may perpetuate a cycle of self-harm. Our review suggests that in recent years there has been little improvement in attitudes toward and experiences of services for patients who self-harm. These findings should be used to reform clinical guidelines and staff training across clinical services to promote patient-centered and compassionate care and deliver more effective, acceptable and accessible services.

The prevalence and severity of loneliness and deficits in perceived social support among who have received a 'personality disorder' diagnosis or have relevant traits: a systematic review.

BACKGROUND: Loneliness and struggles with unmet social needs are a common experience among people with 'personality disorder' diagnoses/traits. Given the impact of loneliness and poor perceived social support on mental health, and the importance of a sense of belonging for recovery, a systematic review examining the prevalence/severity of loneliness and deficits in perceived social support among people with 'personality disorder' diagnoses/traits is an essential step towards developing an intervention targeting the social needs of people with diagnoses/traits 'personality disorder'. Despite an extensive literature on loneliness and deficits of perceived social support among people with 'personality disorder' diagnosis/traits, to date there has been no systematic review of this evidence. METHOD: We conducted a systematic review synthesising quantitative data on the prevalence/severity of loneliness and deficits of perceived social support among people with diagnoses/traits of 'personality disorder' in comparison with other clinical groups and the general population. We searched Medline, Embase, PsycINFO, Web of Social Science, Google scholar and Ethos British Library from inception to December 2021. We conducted quality appraisals using the Joanna Briggs Critical appraisal tools and rated the certainty of evidence using the Grading of Recommendation, Assessment, Development and Evaluation approach. A narrative synthesis was used describing the direction and strength of associations prioritising high quality studies. FINDINGS: A final set of 70 studies are included in this review, most of which are cross-sectional studies (n = 55), based in the United States (51%) and focused on community samples. Our synthesis of evidence found that, across all types of 'personality disorders' (except 'narcissistic personality' traits), people with traits associated with 'personality disorder' or meeting criteria for a diagnosis of 'personality disorder', have higher levels of loneliness, lower perceived relationship satisfaction, and poorer social support than the general population or other clinical samples. CONCLUSION: The quality of evidence is judged as low quality. However, given the distressing nature of loneliness and the known negative effects of loneliness on mental health and recovery, it is important for future research to explore mechanisms by which loneliness may exacerbate 'personality disorder' symptoms and the impact this has on recovery.

Understanding and Defining Young People's Involvement and Under-Representation in Mental Health Research: A Delphi Study.

INTRODUCTION: The mental health of young people (aged 16-25 years) is a growing public health concern in the United Kingdom due to the increasing numbers of young people experiencing mental health difficulties, with many not in contact with mental health services. To design services that meet the needs of all young people, a diversity of young people must be involved in mental health research, beyond being participants. This Delphi study aimed to identify different types of 'involvement' and to define and describe 'under-representation' in young people's involvement in mental health research. METHODS: Twenty-seven experts in young people's mental health research completed a series of online questionnaires. The experts were academic researchers, patient and public involvement (PPI) professionals and young 'experts by experience'. Round 1 generated panellists' views on 'involvement' and 'under-representation'. Round 2 summarised panellists' responses from Round 1 and sought consensus (minimum 70% agreement) in nine question areas. Round 3 validated the findings of the previous rounds. RESULTS: Consensus was achieved in eight out of nine areas, resulting in a matrix (with definitions) of the different types of young people's involvement in mental health research, from being advisors to involvement ambassadors. The findings generated an agreed-upon definition of under-representation, an identification of when in the research process there is under-representation and the characteristics of the young people who are under-represented. Experts further agreed on demographic data that should be collected to improve reporting on involvement. CONCLUSIONS: This study adds to our understanding of involvement and under-representation in the context of young people's mental health research through expert consensus. It provides a practical resource for researchers considering involving young people in the research process and suggests the data that should be collected to improve reporting on the diversity of the young people involved. PATIENT AND PUBLIC CONTRIBUTION: A research oversight group of five young people advised on this study. They contributed throughout the project-from endorsing the research question to commenting on the findings and dissemination. Two of the group reviewed all participant materials and piloted the initial questionnaire.

Shooting yourself in the foot: How immune cells induce antibiotic tolerance in microbial pathogens.

Antibiotic treatment failure of infection is common and frequently occurs in the absence of genetically encoded antibiotic resistance mechanisms. In such scenarios, the ability of bacteria to enter a phenotypic state that renders them tolerant to the killing activity of multiple antibiotic classes is thought to contribute to antibiotic failure. Phagocytic cells, which specialize in engulfing and destroying invading pathogens, may paradoxically contribute to antibiotic tolerance and treatment failure. Macrophages act as reservoirs for some pathogens and impede penetration of certain classes of antibiotics. In addition, increasing evidence suggests that subpopulations of bacteria can survive inside these cells and are coerced into an antibiotic-tolerant state by host cell activity. Uncovering the mechanisms that drive immune-mediated antibiotic tolerance may present novel strategies to improving antibiotic therapy.

Effectiveness of outpatient and community treatments for people with a diagnosis of 'personality disorder': systematic review and meta-analysis.

BACKGROUND: Quality of care and access to effective interventions have been widely criticised as limited for people diagnosed with 'personality disorder' or who have comparable needs (described in some recent papers as "Complex Emotional Needs" (CEN). It is important to identify effective interventions and the optimal context and mode of delivery for people with CEN. We aimed to investigate the effectiveness of psychosocial interventions delivered in community and outpatient settings in treating symptoms associated with 'personality disorder', and the moderating effects of treatment-related variables. METHODS: We systematically searched MEDLINE, EMBASE, PsycINFO, CINAHL, HMIC, ASSIA for articles published in English, from inception to November 23, 2020. We included randomized controlled trials examining interventions provided in community or outpatient settings for CEN. The primary outcome was 'personality disorder' symptoms, while secondary outcomes included anxiety symptoms, depressive symptoms, and global psychiatric symptoms. Random-effects meta-analysis was conducted for each outcome, and meta-regression analysis was performed to assess the moderating effects of treatment characteristics. The quality of the studies and the degree of publication bias was assessed. RESULTS: We included 54 trials (n = 3716 participants) in the meta-analysis. We found a large effect size (g = 0.78, 95% CI: 0.56 to 1.01, p < 0.0001) favoring interventions for 'borderline personality disorder' (BPD) symptoms over Treatment as Usual or Waitlist (TAU/WL), and the efficacy was maintained at follow-up (g = 1.01, 95% CI: 0.37 to 1.65, p = 0.002). Interventions effectively reduced anxiety symptoms (g = 0.58, 95% CI: 0.21 to 0.95, p = 0.002), depressive symptoms (g = 0.57, 95% CI: 0.32 to 0.83, p < 0.0001), and global psychiatric symptoms (g = 0.50, 95% CI: 0.35 to 0.66, p < 0.0001) compared to TAU/WL. The intervention types were equally effective in treating all symptom categories assessed. Treatment duration and treatment intensity did not moderate the effectiveness of the interventions for any outcome. CONCLUSIONS: People with a 'personality disorder' diagnosis benefited from psychological and psychosocial interventions delivered in community or outpatient settings, with all therapeutic approaches showing similar effectiveness. Mental health services should provide people with CEN with specialised treatments in accordance with the availability and the patients' preferences.

Multiple micronutrient supplementation cost-benefit tool for informing maternal nutrition policy and investment decisions.

Antenatal multiple micronutrient supplementation (MMS) is an intervention that can help reach three of the six global nutrition targets, either directly or indirectly: a reduction in low birth weight, stunting, and anaemia in women of reproductive age. To support global guideline development and national decision-making on investments into maternal nutrition, Nutrition International developed a modelling tool called the MMS cost-benefit tool to help users understand whether antenatal MMS is better value for money than iron and folic acid supplementation (IFAS) during pregnancy. The MMS cost-benefit tool can generate estimates on the potential health impact, budget impact, economic value, cost-effectiveness and benefit-cost ratio of investing in MMS compared to IFAS in LMICs. In the 33 countries with data included in the tool, the MMS cost-benefit tool shows that transitioning is expected to generate substantial health benefits in terms of morbidity and mortality averted and can be very cost-effective in multiple scenarios for these countries. The cost per DALY averted averages at US$ 23.61 and benefit-cost ratio ranges from US$ 41-US$ 1304: $1.0, which suggest MMS is good value for money compared with IFAS. With its user-friendly design, open access availability, and online data-driven analytics, the MMS cost-benefit tool can be a powerful resource for governments and nutrition partners seeking timely and evidence-based analyses to inform policy-decision and investments towards the scale-up of MMS for pregnant women globally.

Implementation of Delayed Cord Clamping in public health facilities: a case study from India.

BACKGROUND: Global and country specific recommendations on Delayed umbilical cord clamping (DCC) are available, though guidance on their implementation in program settings is lacking. In India, DCC (clamping not earlier than 1 min after birth) is a component in the package of services delivered as part of the India Newborn Action Plan (INAP) supported by Nutrition International (NI) in two states. The objective of this case study was to document the learnings from implementation of DCC in these two states and to understand the health system factors that affected its operationalization. METHODS: Mixed methods were followed. Using the World Health Organization (WHO) Health Systems building blocks as a framework, 20 Key-Informant Interviews were conducted to explore facilitators and barriers to routine implementation of DCC in public health settings. Existing quantitative program data and secondary data from labour-room registers from eight NI- supported districts were analysed to assess the prevalence of DCC implementation in public health systems settings. RESULTS: A demonstrated commitment from the government to implement DCC at all delivery points in NI supported districts was observed. Funds were sufficient, trainings were optimal, knowledge of the health workforce was adequate and a recording mechanism was in place. According to record reviews, DCC was more likely to happen in facilities that provide Basic Emergency Obstetric services and among normal deliveries. It was less likely to be followed in babies delivered by Caesarean section (OR 0.03; 95%CI 0.02,0.05), birthweight < 2000 g (OR 0.22; 95%CI 0.12,0.47), multiple pregnancies (OR 0.17, 95%CI 0.05,0.63), birth asphyxia requiring resuscitation (0.37; 95%CI 0.26,0.52), and those delivered during day shift (OR 0.59, 95%CI 0.40, 0.83). CONCLUSIONS: Wide coverage of DCC in public health settings in the two states was observed. Good governance, adequate funding, commitment of health workforce has likely contributed to its success in these contexts. These are critical elements to guide DCC implementation in India and for consideration in other settings.

Personality traits and night eating syndrome in women with bulimia nervosa and binge eating disorder.

PURPOSE: Previous research suggests that eating disorders may be associated with certain personality profiles; however, there is limited research investigating associations with night eating syndrome (NES). This research suggests harm avoidance personality trait is higher in NES individuals than in the general population, however, evidence of associations with other personality traits is inconsistent. To understand which personality traits are associated with NES symptoms, the current study aimed to improve understanding of the relationship between NES symptoms and a range of personality traits, addressing limitations in the earlier literature in this area by controlling for common confounders. METHODS: Baseline data were analysed from an outpatient psychotherapy trial for 111 women with bulimia nervosa or binge eating disorder. Pre-treatment measures of personality traits (measured with the Temperament and character inventory-revised) and NES symptoms (measured with the Night eating questionnaire) were used. Regression analyses tested associations between these variables, adjusting for potential confounders, including age and ethnicity. RESULTS: Low cooperativeness scores were associated with greater NES symptoms in the multivariable model (mean difference: - 0.10, 95% confidence intervals: - 0.20 to - 0.01, p = 0.033). There was weak evidence of associations between both high harm avoidance and low self-directedness personality traits and greater NES symptoms. CONCLUSIONS: This study adds to the limited research measuring associations between a range of personality traits and NES, addressing limitations of previous research. Weak evidence for an association between high harm avoidance and low self-directedness and increased NES symptoms was found. A novel association was found between low cooperativeness and greater NES symptoms. Further research is needed to validate its presence in those with and without comorbid eating disorders and to examine the relative change in NES, eating disorder symptoms and personality scores in treatments focusing on cooperativeness. LEVEL OF EVIDENCE: Level IV (cross-sectional data from a randomised controlled trial, CTB/04/08/139).

Recalcitrant Staphylococcus aureus Infections: Obstacles and Solutions.

Antibiotic treatment failure of Staphylococcus aureus infections is very common. In addition to genetically encoded mechanisms of antibiotic resistance, numerous additional factors limit the efficacy of antibiotics in vivo Identifying and removing the barriers to antibiotic efficacy are of major importance, as even if new antibiotics become available, they will likely face the same barriers to efficacy as their predecessors. One major obstacle to antibiotic efficacy is the proficiency of S. aureus to enter a physiological state that is incompatible with antibiotic killing. Multiple pathways leading to antibiotic tolerance and the formation of tolerant subpopulations called persister cells have been described for S. aureus Additionally, S. aureus is a versatile pathogen that can infect numerous tissues and invade a variety of cell types, of which some are poorly penetrable to antibiotics. It is therefore unlikely that there will be a single solution to the problem of recalcitrant S. aureus infection. Instead, specific approaches may be required for targeting tolerant cells within different niches, be it through direct targeting of persister cells, sensitization of persisters to conventional antibiotics, improved penetration of antibiotics to particular niches, or any combination thereof. Here, we examine two well-described reservoirs of antibiotic-tolerant S. aureus, the biofilm and the macrophage, the barriers these environments present to antibiotic efficacy, and potential solutions to the problem.

Macrophage-Produced Peroxynitrite Induces Antibiotic Tolerance and Supersedes Intrinsic Mechanisms of Persister Formation.

Staphylococcus aureus is a leading human pathogen that frequently causes chronic and relapsing infections. Antibiotic-tolerant persister cells contribute to frequent antibiotic failure in patients. Macrophages represent an important niche during S. aureus bacteremia, and recent work has identified a role for oxidative burst in the formation of antibiotic-tolerant S. aureus. We find that host-derived peroxynitrite, the reaction product of superoxide and nitric oxide, is the main mediator of antibiotic tolerance in macrophages. Using a collection of S. aureus clinical isolates, we find that, despite significant variation in persister formation in pure culture, all strains were similarly enriched for antibiotic tolerance following internalization by activated macrophages. Our findings suggest that host interaction strongly induces antibiotic tolerance and may negate bacterial mechanisms of persister formation established in pure culture. These findings emphasize the importance of studying antibiotic tolerance in the context of bacterial interaction with the host and suggest that modulation of the host response may represent a viable therapeutic strategy to sensitize S. aureus to antibiotics.

Marine Actinomycetes, New Sources of Biotechnological Products.

The Actinomycetales order is one of great genetic and functional diversity, including diversity in the production of secondary metabolites which have uses in medical, environmental rehabilitation, and industrial applications. Secondary metabolites produced by actinomycete species are an abundant source of antibiotics, antitumor agents, anthelmintics, and antifungals. These actinomycete-derived medicines are in circulation as current treatments, but actinomycetes are also being explored as potential sources of new compounds to combat multidrug resistance in pathogenic bacteria. Actinomycetes as a potential to solve environmental concerns is another area of recent investigation, particularly their utility in the bioremediation of pesticides, toxic metals, radioactive wastes, and biofouling. Other applications include biofuels, detergents, and food preservatives/additives. Exploring other unique properties of actinomycetes will allow for a deeper understanding of this interesting taxonomic group. Combined with genetic engineering, microbial experimental evolution, and other enhancement techniques, it is reasonable to assume that the use of marine actinomycetes will continue to increase. Novel products will begin to be developed for diverse applied research purposes, including zymology and enology. This paper outlines the current knowledge of actinomycete usage in applied research, focusing on marine isolates and providing direction for future research.

Pseudomonas aeruginosa exoproducts determine antibiotic efficacy against Staphylococcus aureus.

Chronic coinfections of Staphylococcus aureus and Pseudomonas aeruginosa frequently fail to respond to antibiotic treatment, leading to significant patient morbidity and mortality. Currently, the impact of interspecies interaction on S. aureus antibiotic susceptibility remains poorly understood. In this study, we utilize a panel of P. aeruginosa burn wound and cystic fibrosis (CF) lung isolates to demonstrate that P. aeruginosa alters S. aureus susceptibility to bactericidal antibiotics in a variable, strain-dependent manner and further identify 3 independent interactions responsible for antagonizing or potentiating antibiotic activity against S. aureus. We find that P. aeruginosa LasA endopeptidase potentiates lysis of S. aureus by vancomycin, rhamnolipids facilitate proton-motive force-independent tobramycin uptake, and 2-heptyl-4-hydroxyquinoline N-oxide (HQNO) induces multidrug tolerance in S. aureus through respiratory inhibition and reduction of cellular ATP. We find that the production of each of these factors varies between clinical isolates and corresponds to the capacity of each isolate to alter S. aureus antibiotic susceptibility. Furthermore, we demonstrate that vancomycin treatment of a S. aureus mouse burn infection is potentiated by the presence of a LasA-producing P. aeruginosa population. These findings demonstrate that antibiotic susceptibility is complex and dependent not only upon the genotype of the pathogen being targeted, but also on interactions with other microorganisms in the infection environment. Consideration of these interactions will improve the treatment of polymicrobial infections.

Global prevalence and risk factors for mental health problems in police personnel: a systematic review and meta-analysis.

Police face an increased risk of developing mental health problems, yet reliable estimates of their psychological difficulties remain unknown. This systematic review and meta-analysis estimate the pooled prevalence and risk factors for mental health problems among police personnel worldwide. Three independent reviewers searched 16 databases and screened 11 506 articles published between January 1980 and October 2019. Eligible studies involved at least 100 active police professionals and used validated instruments to ascertain specific mental health problems. Estimates were pooled using random-effects meta-analyses. In total, 60 cross-sectional and seven longitudinal studies, involving 272 463 police personnel from 24 countries met criteria for inclusion. The overall pooled point prevalence was 14.6% for depression (95% CI 10.9% to 18.6%), 14.2% for post-traumatic stress disorder (PTSD; 95% CI 10.3% to 18.7%), 9.6% for a generalised anxiety disorder (95% CI 6.7% to 12.9%), 8.5% for suicidal ideation (95% CI 6.1% to 11.2%), 5.0% for alcohol dependence (95% CI 3.5% to 6.7%) and 25.7% for hazardous drinking (95% CI 19.6% to 32.4%). The strongest risk factor for depression and suicidal ideation was higher occupational stress, and the strongest risk factors for PTSD were higher occupational stress and avoidant coping strategies. Higher levels of peer-support were associated with significantly lower PTSD symptoms. Our findings suggest that the prevalence of mental health problems among police exceeds twice that previously reported in mixed samples of first responders, and is associated with poor social support, occupational stress and maladaptive coping strategies. Without effective intervention, psychological difficulties will remain a substantial health concern among police.

What are the barriers, facilitators and interventions targeting help-seeking behaviours for common mental health problems in adolescents? A systematic review.

BACKGROUND: Increasing rates of mental health problems among adolescents are of concern. Teens who are most in need of mental health attention are reluctant to seek help. A better understanding of the help-seeking in this population is needed to overcome this gap. METHODS: Five databases were searched to identify the principal barriers, facilitators and interventions targeting help-seeking for common mental health problems in adolescents aged 10-19 years. The search was performed in June 2018 and updated in April 2019. Two independent screening processes were made using the eligibility criteria. Quality assessment of each study was performed, and findings summarised using a narrative synthesis. RESULTS: Ninety studies meet the inclusion criteria for this review for barrier and facilitators (n = 54) and interventions (n = 36). Stigma and negative beliefs towards mental health services and professionals were the most cited barriers. Facilitators included previous positive experience with health services and mental health literacy. Most interventions were based on psychoeducation, which focused on general mental health knowledge, suicide and self-harm, stigma and depression. Other types of interventions included the use of multimedia and online tools, peer training and outreach initiatives. Overall, the quality of studies was low to medium and there was no general agreement regarding help-seeking definition and measurements. CONCLUSION: Most of the interventions took place in an educational setting however, it is important to consider adolescents outside the educational system. Encouraging help-seeking should come with the increased availability of mental health support for all adolescents in need, but this is still a major challenge for Child and Adolescent Mental Health Services. There is also a need to develop shared definitions, theoretical frameworks and higher methodological standards in research regarding help-seeking behaviours in adolescents. This will allow more consistency and generalisability of findings, improving the development of help-seeking interventions and ensuring timely access to mental health treatments.

Unleashing talent in mental health sciences: gender equality at the top.

Society is undergoing a shift in gender politics. Science and medicine are part of this conversation, not least as women's representation and pay continue to drop as one progresses through more senior academic and clinical levels. Naming and redressing these inequalities needs to be a priority for us all.Declaration of interestNone.

Impact of paternal deployment to the conflicts in Iraq and Afghanistan and paternal post-traumatic stress disorder on the children of military fathers.

BACKGROUND: Little is known about the social and emotional well-being of children whose fathers have been deployed to the conflicts in Iraq/Afghanistan or who have post-traumatic stress disorder (PTSD).AimsTo examine the emotional and behavioural well-being of children whose fathers are or have been in the UK armed forces, in particular the effects of paternal deployment to the conflicts in Iraq or Afghanistan and paternal PTSD. METHOD: Fathers who had taken part in a large tri-service cohort and had children aged 3-16 years were asked about the emotional and behavioural well-being of their child(ren) and assessed for symptoms of PTSD via online questionnaires and telephone interview. RESULTS: In total, 621 (67%) fathers participated, providing data on 1044 children. Paternal deployment to Iraq or Afghanistan was not associated with childhood emotional and behavioural difficulties. Paternal probable PTSD were associated with child hyperactivity. This finding was limited to boys and those under 11 years of age. CONCLUSIONS: This study showed that adverse childhood emotional and behavioural well-being was not associated with paternal deployment but was associated with paternal probable PTSD.Declaration of interestN.T.F. is a trustee of the Warrior Programme, a charity supporting ex-service personnel and their families. She is also a member of the Independent Group Advising on the Release of Data (IGARD). S.W. is a trustee of Combat Stress, a charity supporting ex-service personnel and their families, and President of the Royal Society of Medicine. S.W. is partially funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emergency Preparedness and Response at King's College London in partnership with Public Health England (PHE), in collaboration with the University of East Anglia and Newcastle University.