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Abstract BackgroundWhile patient and public involvement and engagement (PPIE) is now seen as a cornerstone of mental health research, young people’s involvement in PPIE faces limitations. Work and school demands and more limited independence can make it challenging for young people to engage with PPIE. Lack of ability or desire to attend face-to-face meetings or group discussions can further compound this difficulty. The VoiceIn app and digital platform were codeveloped by a multidisciplinary team of young people, mental health researchers, and software designers, and enables young people to engage directly with PPIE opportunities via a mobile app. ObjectiveThis paper aims to describe how VoiceIn was developed through a series of co-design workshops with relevant stakeholders, specifically (1) how the initial design of VoiceIn was informed and driven by focus groups with young people, mental health professionals, and PPIE leads; (2) how VoiceIn was refined through collaboration with the aforementioned stakeholders; (3) the priorities for an app to support PPIE; (4) the key features necessary in the PPIE app; and (5) the recommended next steps in testing and deploying the digital platform. MethodsInitial co-design workshops took place with young people, mental health professionals, and PPIE leads to identify key features of an app to support PPIE. A series of VoiceIn design prototypes were developed and iterated based on the priorities and preferences of the stakeholders. The MoSCoW (must have, should have, could have, won’t have) prioritization method was used throughout the process to identify priorities across the different stakeholder groups. ResultsCo-design with young people, mental health professionals, and PPIE leads supported the successful development and improvement of the VoiceIn app. As a result of this process, key features were identified, including allowing for various modes of providing feedback (eg, polls and comments), reviewing project updates, and expressing interest in categories of research. The researcher platform was developed to support multimedia uploads for project descriptions; a jargon detector; a dedicated section for providing project updates; and a visually appealing, user-friendly design. While all stakeholder groups emphasized the importance of allowing app users to engage with the app in various ways and for there to be ongoing progress updates, group differences were also noticed. Young people expressed a desire for incentives and rewards for engaging with the app (eg, to post on their public social media profiles), and mental health professionals and PPIE leads prioritized flexibility in describing the project and its PPIE needs. ConclusionsA co-design approach was pivotal to the development of the VoiceIn app. This collaborative approach enabled the app to meet the divergent needs of young people, mental health professionals, and PPIE leads. This process mirrored the aspirations of PPIE initiatives by cocreating a digital health research tool with key stakeholders.

BackgroundPharmacogenetics can impact patient care and outcomes through personalizing the selection of medicines, resulting in improved efficacy and a reduction in harmful side effects. Despite the existence of compelling clinical evidence and international guidelines highlighting the benefits of pharmacogenetics in clinical practice, implementation within the National Health Service in the United Kingdom is limited. An important barrier to overcome is the development of IT solutions that support the integration of pharmacogenetic data into health care systems. This necessitates a better understanding of the role of electronic health records (EHRs) and the design of clinical decision support systems that are acceptable to clinicians, particularly those in primary care. ObjectiveExplore the needs and requirements of a pharmacogenetic service from the perspective of primary care clinicians with a view to co-design a prototype solution. MethodsWe used ethnographic and think-aloud observations, user research workshops, and prototyping. The participants for this study included general practitioners and pharmacists. In total, we undertook 5 sessions of ethnographic observation to understand current practices and workflows. This was followed by 3 user research workshops, each with its own topic guide starting with personas and early ideation, through to exploring the potential of clinical decision support systems and prototype design. We subsequently analyzed workshop data using affinity diagramming and refined the key requirements for the solution collaboratively as a multidisciplinary project team. ResultsUser research results identified that pharmacogenetic data must be incorporated within existing EHRs rather than through a stand-alone portal. The information presented through clinical decision support systems must be clear, accessible, and user-friendly as the service will be used by a range of end users. Critically, the information should be displayed within the prescribing workflow, rather than discrete results stored statically in the EHR. Finally, the prescribing recommendations should be authoritative to provide confidence in the validity of the results. Based on these findings we co-designed an interactive prototype, demonstrating pharmacogenetic clinical decision support integrated within the prescribing workflow of an EHR. ConclusionsThis study marks a significant step forward in the design of systems that support pharmacogenetic-guided prescribing in primary care settings. Clinical decision support systems have the potential to enhance the personalization of medicines, provided they are effectively implemented within EHRs and present pharmacogenetic data in a user-friendly, actionable, and standardized format. Achieving this requires the development of a decoupled, standards-based architecture that allows for the separation of data from application, facilitating integration across various EHRs through the use of application programming interfaces (APIs). More globally, this study demonstrates the role of health informatics and user-centered design in realizing the potential of personalized medicine at scale and ensuring that the benefits of genomic innovation reach patients and populations effectively.

Abstract Background Acute respiratory distress syndrome (ARDS) is a leading cause of morbidity and mortality in the intensive care unit. Biochemical markers of cardiac dysfunction are associated with high mortality in many respiratory conditions. The aim of this systematic review is to examine the link between elevated biomarkers of cardiac dysfunction in ARDS and mortality. Methods A systematic review of MEDLINE, EMBASE, Web of Science and CENTRAL databases was performed. We included studies of adult intensive care patients with ARDS that reported the risk of death in relation to a measured biomarker of cardiac dysfunction. The primary outcome of interest was mortality up to 60 days. A random-effects model was used for pooled estimates. Funnel-plot inspection was done to evaluate publication bias; Cochrane chi-square tests and I 2 tests were used to assess heterogeneity. Results Twenty-two studies were included in the systematic review and 18 in the meta-analysis. Biomarkers of cardiac stretch included NT-ProBNP (nine studies) and BNP (six studies). Biomarkers of cardiac injury included Troponin-T (two studies), Troponin-I (one study) and High-Sensitivity-Troponin-I (three studies). Three studies assessed multiple cardiac biomarkers. High levels of NT-proBNP and BNP were associated with a higher risk of death up to 60 days (unadjusted OR 8.98; CI 4.15-19.43; p

BACKGROUND:Recent studies have uncovered a peculiar finding: that the strength and dimensionality of depression symptoms' inter-relationships vary systematically across study samples with different average levels of depression severity. Our aim was to examine whether this phenomenon is driven by the proportion of non-affected subjects in the sample. METHODS:Cross-sectional data from the "Cohort Study on Substance Use Risk Factors" was analyzed. Self-reported depression symptoms were assessed via the Major Depressive Inventory. Symptom data were analyzed via polychoric correlations, principal component analysis, confirmatory factor analysis, Mokken scale analysis, and network analysis. Analyses were carried out across 22 subsamples containing increasingly higher proportions of non-depressed participants. Results were examined as a function of the proportion of non-depressed participants. RESULTS:A strong influence of the proportion of non-depressed participants was uncovered: the higher the proportion, the stronger the symptom correlations, higher their tendency towards unidimensionality, better their scalability, and higher the network edge strengths. Comparing the depressed sample with the general population sample, the average symptom correlation increased from 0.29 to 0.51; variance explained by the first eigenvalue increased from 0.36 to 0.56; fit measures from confirmatory one-factor analysis increased from 0.81 to 0.97; the H coefficient of scalability increased from 0.26 to 0.48; and the median network edge increased from 0.00 to 0.07. CONCLUSIONS:Results of psychometric analyses vary substantially as a function of the proportion of non-depressed participants in the sample being studied. This provides a possible explanation for the lack of reproducibility of previous psychometric studies.

(a) objectiveThis study aimed to identify trajectories of alcohol use (AU) and their associations with the development of alcohol use disorder (AUD) among young men with different weekly drinking patterns.(b) methodA longitudinal latent class analysis integrating several aspects of AU, such as drinking quantity and frequency on weekends vs workweek days, involving 4719 young Swiss men at ages 20, 21, and 25, and collected by the Cohort Study on Substance Use Risk Factors, was used to identify different AU trajectories over time. The development of AUD scores in these trajectories was investigated using generalized linear mixed models.(c) resultsSix AU trajectory classes, similar to those described in the literature, were identified: 'abstainers-light drinkers', 'light workweek increasers', 'light decreasers', 'moderate weekend decreasers', 'moderate workweek increasers', and 'heavy drinkers'. Only 12% of participants were assigned to a trajectory class with decreasing AU associated with a decline in their AUD score. AUD scores increased in trajectory classes exhibiting increasing AU on workweek days, despite low and moderate general AU. Finally, more than 59% of participants were on an AU trajectory presenting no change in their mean AUD score over time.(d) conclusionsMaturing out of problematic AU in emerging adulthood is not the norm in Switzerland, and the AUD score developed in late adolescence remains until at least emerging adulthood. AU on workweek days is a more practical marker of potentially problematic AU. This calls for timely interventions in adolescence and concerning regular drinking on workweek days in emerging adulthood.

Background and objective: The aims of this study were to estimate the lifetime and 12-month prevalence of exposure to potentially traumatic events (PTEs) in young men in Switzerland and to assess factors and mental health outcomes associated with such events. Method: Data were drawn from the Cohort Study on Substance Use Risk Factors (C-SURF), encompassing 5,223 young men. Exposure to PTEs was assessed using the Post-traumatic Diagnostic Scale (PDS), Trauma History Questionnaire (THQ) and Life Event Checklist (LEC). Results: Lifetime prevalence of PTEs was 59.4%, with 37.3% reporting multiple types of events. Twelve-month prevalence was 31.2%, with 12.7% reporting multiple types of events. Low education level of participants, high maternal education, family affluence below average, and not living with biological parents were associated with a higher risk of having experienced one or more PTEs in one’s lifetime. Low education level of participants and high maternal education were also related to exposure to one or more PTEs over the past 12 months. Logistic regression analyses demonstrated that PTE exposure was directly associated with all assessed mental health outcomes. The strongest relationship was found between exposure to multiple types of PTEs and suicide attempts (adjusted OR 4.9 [95% CI: 2.9–8.4]). Conclusions: These results indicate that having experienced one or multiple types of PTEs is common in Swiss young men. Efforts should be intensified to reduce exposure to PTEs and prevent and treat resulting problematic mental health outcomes in young adults.

Positive social interactions are crucial for human well-being. Elevated prenatal exposure to testosterone as indicated by a low second-to-fourth finger length ratio (2D:4D) relates to more aggressive/hostile behavior in men of low 2D:4D, especially in challenging situations. How much people enjoy interacting with others is determined by the personality trait sociability. Given its role in approach and avoidance behavior, sociability might also be influenced by prenatal sex hormones, but studies are inconclusive so far. Here, we investigated the association between 2D:4D and the personality trait sociability complemented by personal social capital and personal social network size, in a population-based cohort of 4998 men. Lower 2D:4D correlated significantly with higher trait sociability, bigger personal social capital, and larger personal social network size. These effects were consistent across both hands separately and their mean value. Furthermore, both factors of sociability (1) liking party and company of friends and (2) isolation intolerance, correlated significantly with the prenatal testosterone marker. The exploratory analysis revealed no link between 2D:4D and responses to the personality trait aggression items or items of anti-social-personality disorder. Our data suggest that prenatal androgen exposure organizes the brain with lasting effects on social behavior.

Most bacterial glycoproteins identified to date are virulence factors of pathogenic bacteria, i.e. adhesins and invasins. However, the impact of protein glycosylation on the major human pathogen Staphylococcus aureus remains incompletely understood. To study protein glycosylation in staphylococci, we analyzed lysostaphin lysates of methicillin-resistant Staphylococcus aureus (MRSA) strains by SDS-PAGE and subsequent periodic acid-Schiff's staining. We detected four (>300, ∼250, ∼165, and ∼120 kDa) and two (>300 and ∼175 kDa) glycosylated surface proteins with strain COL and strain 1061, respectively. The ∼250, ∼165, and ∼175 kDa proteins were identified as plasmin-sensitive protein (Pls) by mass spectrometry. Previously, Pls has been demonstrated to be a virulence factor in a mouse septic arthritis model. The pls gene is encoded by the staphylococcal cassette chromosome (SCC)mec type I in MRSA that also encodes the methicillin resistance-conferring mecA and further genes. In a search for glycosyltransferases, we identified two open reading frames encoded downstream of pls on the SCCmec element, which we termed gtfC and gtfD. Expression and deletion analysis revealed that both gtfC and gtfD mediate glycosylation of Pls. Additionally, the recently reported glycosyltransferases SdgA and SdgB are involved in Pls glycosylation. Glycosylation occurs at serine residues in the Pls SD-repeat region and modifying carbohydrates are N-acetylhexosaminyl residues. Functional characterization revealed that Pls can confer increased biofilm formation, which seems to involve two distinct mechanisms. The first mechanism depends on glycosylation of the SD-repeat region by GtfC/GtfD and probably also involves eDNA, while the second seems to be independent of glycosylation as well as eDNA and may involve the centrally located G5 domains. Other previously known Pls properties are not related to the sugar modifications. In conclusion, Pls is a glycoprotein and Pls glycosyl residues can stimulate biofilm formation. Thus, sugar modifications may represent promising new targets for novel therapeutic or prophylactic measures against life-threatening S. aureus infections.

BACKGROUND:Staphylococci belong to the most important pathogens causing implant-associated infections. Colonization of the implanted medical devices by the formation of a three-dimensional structure made of bacteria and host material called biofilm is considered the most critical factor in these infections. To form a biofilm, bacteria first attach to the surface of the medical device, and then proliferate and accumulate into multilayered cell clusters. Biofilm accumulation may be mediated by polysaccharide and protein factors. METHODOLOGY/PRINCIPAL FINDINGS:The information on Staphylococcus aureus protein factors involved in biofilm accumulation is limited, therefore, we searched the S. aureus Col genome for LPXTG-motif containing potential surface proteins and chose the so far uncharacterized S. aureus surface protein C (SasC) for further investigation. The deduced SasC sequence consists of 2186 amino acids with a molecular mass of 238 kDa and has features typical of gram-positive surface proteins, such as an N-terminal signal peptide, a C-terminal LPXTG cell wall anchorage motif, and a repeat region consisting of 17 repeats similar to the domain of unknown function 1542 (DUF1542). We heterologously expressed sasC in Staphylococcus carnosus, which led to the formation of huge cell aggregates indicative of intercellular adhesion and biofilm accumulation. To localize the domain conferring cell aggregation, we expressed two subclones of sasC encoding either the N-terminal domain including a motif that is found in various architectures (FIVAR) or 8 of the DUF1542 repeats. SasC or its N-terminal domain, but not the DUF1542 repeat region conferred production of huge cell aggregates, higher attachment to polystyrene, and enhanced biofilm formation to S. carnosus and S. aureus. SasC does not mediate binding to fibrinogen, thrombospondin-1, von Willebrand factor, or platelets as determined by flow cytometry. CONCLUSIONS/SIGNIFICANCE:Thus, SasC represents a novel S. aureus protein factor involved in cell aggregation and biofilm formation, which may play an important role in colonization during infection with this important pathogen.