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Andrew Walkden, James F Young, Anne F Spencer, Jane AshworthManchester Royal Eye Hospital, Manchester, UKProblem: Starting ophthalmic specialty training can be daunting as new basic clinical examination and surgical skills must be acquired before meaningful assessment of patients can begin. No formal clinical induction currently exists with the aim to teach clinical and practical skills to new starters.Aim and objectives: To determine the experience and needs of ophthalmic trainees entering into specialist training. Using this information we developed and implemented a clinical skills training programme for Ophthalmology ST1s.Intervention: Using SMART objectives, PDSA cycles and Chartered Institute of Personnel Development guidance we implemented a clinical skills induction week. Pre-course skills evaluation took place in the form of a questionnaire in order to tailor the course content to the skill level of the group. Course material was made and simulation techniques devised for teaching practical skills. Qualitative data was collected via a pre- and post-course questionnaire.Outcome: All 9 participants rated the course as “extremely useful” it increased their confidence in terms of commencing clinical ophthalmology. 100% of participants felt that this course should be delivered to new ST1s. All participants reported improved confidence in managing ophthalmic emergencies and their clinical skills technique.Lessons learned: A sustainable induction programme was implemented tailored to the prior experience and skills of ST1 trainees. All participants felt it improved their confidence and clinical skills prior to commencing clinical activities. Basic clinical skills can be taught in a cost effective manner early on in postgraduate training.Keywords: ophthalmic training, starting ophthalmology, ophthalmology run-through training, ophthalmic clinical skills, ophthalmic training needs

The current vaccine against tuberculosis, Mycobacterium bovis strain bacille Calmette-Guerin (BCG), offers potential advantages as a live, innately immunogenic vaccine vehicle for the expression and delivery of protective recombinant antigens (Stover, C.K., V.F. de la Cruz, T.R. Fuerst, J.E. Burlein, L.A. Benson, L.T. Bennett, G.P. Bansal, J.F. Young, M.H. Lee, G.F. Hatfull et al. 1991. Nature [Lond]. 351:456; Jacobs, W.R., Jr., S.B. Snapper, L. Lugosi and B.R. Bloom. 1990. Curr. Top. Microbiol. Immunol. 155:153; Jacobs, W.R., M. Tuckman, and B.R. Bloom. 1987. Nature [Lond.]. 327:532); but as an attenuated intracellular bacterium residing in macrophages, BCG would seem to be best suited for eliciting cellular responses and not humoral responses. Since bacterial lipoproteins are often among the most immunogenic of bacterial antigens, we tested whether BCG expression of a target antigen as a membrane-associated lipoprotein could enhance the potential for a recombinant BCG vaccine to elicit high-titered protective antibody responses to target antigens. Immunization of mice with recombinant BCG vaccines expressing the outer surface protein A (OspA) antigen of Borrelia burgdorferi as a membrane-associated lipoprotein resulted in protective antibody responses that were 100-1,000-fold higher than responses elicited by immunization with recombinant BCG expressing OspA cytoplasmically or as a secreted fusion protein. Furthermore, these improved antibody responses were observed in heterogeneous mouse strains that vary in their immune responsiveness to OspA and sensitivity to BCG growth. Thus, expression of protective antigens as chimeric membrane-associated lipoproteins on recombinant BCG may result in the generation of new candidate vaccines against Lyme borreliosis and other human or veterinary diseases where humoral immunity is the protective response.

Objective: To examine short-term (i.e., postintervention) outcomes from a randomized controlled trial comparing a school-based telehealth-delivered depression prevention program, Interpersonal Psychotherapy-Adolescent Skills Training (IPT-AST), to services as usual (SAU). We expected IPT-AST would be acceptable and feasible and that IPT-AST adolescents would experience greater reductions in depression symptoms, anxiety symptoms, and impairment compared with SAU., Method: Adolescents ( N = 242; M age = 14.80 years, SD = 0.70; 65% female; 21% Black; 13% Hispanic/Latinx) with elevated scores on the Center for Epidemiologic Studies Depression Scale (Radloff, 1977) at screening provided data at baseline, 2-month (midpoint of IPT-AST), and 3-month (postintervention) assessments. They reported depression symptoms on the Center for Epidemiologic Studies Depression Scale, anxiety symptoms on the Screen for Child Anxiety Related Emotional Disorders (Birmaher et al., 1997), and impairment on the Columbia Impairment Scale (Bird et al., 1993). Baseline depression diagnosis was examined as a moderator., Results: Hierarchical linear models showed that adolescents reported significant reductions in depression symptoms and impairment across conditions. IPT-AST adolescents reported significantly greater reductions in anxiety symptoms than SAU adolescents, d = .39, 95% CI [.05, .72], p = .003. Depression diagnosis moderated outcomes ( d s = .33-.34, p s ≤ .05), such that IPT-AST adolescents without a diagnosis at baseline showed greater improvements in depression and anxiety symptoms than SAU adolescents. Adolescents in SAU with a depression diagnosis at baseline showed greater improvements in impairment compared with IPT-AST. Attendance and satisfaction data demonstrated the feasibility and acceptability of telehealth-delivered IPT-AST., Conclusions: Results support telehealth-delivered IPT-AST as a promising intervention for improving short-term outcomes among adolescents with depression symptoms but without a depression diagnosis. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Clinician distress about working with patients at risk for suicide is well documented in the literature, yet little work has examined its pervasiveness across clinical settings. We conducted a secondary analysis of qualitative data gathered from 26 clinicians in primary care and outpatient mental health clinics serving both adult and child clients on their perception of evidence-based practice use for suicide screening, assessment, and brief intervention. Qualitative data were coded for any mentions of clinician anxiety or emotional response, and brief quantitative measures were collected to characterize our sample. When discussing broader barriers to implementation, 85% of participants spontaneously mentioned anxiety or heightened emotional responses related to delivering suicide prevention practices to those at risk for suicide. Common themes included low self-efficacy in suicide prevention skills, distress related to escalating care, efforts to alleviate such distress, and difficulty related to tolerating the uncertainty inherent in suicide prevention work. Similarly, while standardized anxiety ratings for participants were consistent with those of non-clinical norming samples, clinicians reported mild to moderate anxiety when screening for suicide risk (M = 3.64, SD = 2.19, Range = 0-8) and engaging in safety planning (M = 4.1, SD = 2.88, Range = 1-7) on post-interview surveys. In contrast, survey responses reflected generally high self-efficacy in their ability to screen for suicide risk (M = 7.66, SD = 1.29, Range = 5.25-10) and engage in safety planning (M = 8.25, SD = 0.87, Range = 7-9.5). Findings highlight pervasiveness of clinician distress when implementing suicide prevention practices and can inform future suicide prevention implementation efforts., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: Suicide is a leading cause of death in US youths., Objective: To assess whether screening with supplemental items 10 to 13 on the Patient Health Questionnaire-9 modified for teens (PHQ-9M) improves prediction of youth suicide attempts beyond the information provided by the first 9 items alone (the PHQ-9)., Design, Setting, and Participants: This retrospective cohort study used a retrospective cohort of adolescents aged 12 to 17 years who were screened for depression in outpatient facilities within a pediatric health care system between January 1, 2016, and December 31, 2022, with up to 1 year of follow-up to assess the occurrence of suicidal behavior. Follow-up was completed on December 31, 2023., Exposure: Screening with the PHQ-9M., Main Outcomes and Measures: This study developed and compared prediction using 3 Cox proportional hazards regression models (CR-9, CR-13, and CR-3) of subsequent suicide attempts, determined by the hospital's electronic health records up to 1 year following the last PHQ-9M screening. The CR-9 model used the PHQ-9 and the CR-13 model used all 13 items of PHQ-9M. The CR-3 model used the 3 most impactful variables selected from the 13 PHQ-9M items and PHQ-9 total score. All models were evaluated across 4 prediction horizons (30, 90, 180, and 365 days) following PHQ-9M screenings. Evaluation metrics were the area under the receiver operating characteristic curve (AUROC) and the area under the precision recall curve (AUPRC)., Results: Of 130 028 outpatients (65 520 [50.4%] male) with 272 402 PHQ-9M screenings, 549 (0.4%) had subsequent suicide attempts within 1 year following the PHQ-9M screening. The AUROC of the CR-9 model in the 365-day horizon was 0.77 (95% CI, 0.75-0.79); of the CR-13 model, 0.80 (95% CI, 0.78-0.82); and of the CR-3 model, 0.79 (95% CI, 0.76-0.81); the AUPRC of the CR-9 model was 0.02 (95% CI, 0.02-0.03); of the CR-13 model, 0.03 (95% CI, 0.02-0.03); and of the CR-3 model, 0.02 (95% CI, 0.02-0.03). The 3 most impactful items using adjusted hazard ratios were supplemental item 13 (lifetime suicide attempts; 3.06 [95% CI, 2.47-3.80]), supplemental item 10 (depressed mood severity in the past year; 2.99 [95% CI, 2.32-3.86]), and supplemental item 12 (serious suicidal ideation in the past month; 1.63 [95% CI, 1.25-2.12]). All of the models achieved higher AUROCs as prediction horizons shortened., Conclusions and Relevance: In this cohort study of adolescent PHQ-9M screenings, the supplemental items on PHQ-9M screening improved prediction of youth suicide attempts compared with screening using the PHQ-9 across all prediction horizons, suggesting that PHQ-9M screening should be considered during outpatient visits to improve prediction of suicide attempts.

As food transits the gastrointestinal tract, food structures are disrupted and nutrients are absorbed across the gut barrier. In the past decade, great efforts have focused on the creation of a consensus gastrointestinal digestion protocol (i.e., INFOGEST method) to mimic digestion in the upper gut. However, to better determine the fate of food components, it is also critical to mimic food absorption in vitro . This is usually performed by treating polarized epithelial cells (i.e., differentiated Caco-2 monolayers) with food digesta. This food digesta contains digestive enzymes and bile salts, and if following the INFOGEST protocol, at concentrations that although physiologically relevant are harmful to cells. The lack of a harmonized protocol on how to prepare the food digesta samples for downstream Caco-2 studies creates challenges in comparing inter laboratory results. This article aims to critically review the current detoxification practices, highlight potential routes and their limitations, and recommend common approaches to ensure food digesta is biocompatible with Caco-2 monolayers. Our ultimate aim is to agree a harmonized consensus protocol or framework for in vitro studies focused on the absorption of food components across the intestinal barrier.

This study investigates the structure of factors that influence consumer intentions to both try and to consume cultured proteins, and their intentions to substitute vegan, vegetarian and omnivore diets with these alternative protein sources. Comprehensive survey data (N = 3862) was collected from three Nordic countries (Denmark, Finland, and Norway) and analysed using confirmatory factor analysis and structural equation modelling. Theoretically, this article draws from behavioural models of environmental psychology, identity theory, and attitude theory. Results indicate that beliefs about the necessity of an industry producing cultured proteins and impacts of cultured proteins on the global economy are significant predictors of consumer intentions. Moreover, participants who exhibited high levels of general and food innovativeness were more likely to express positive intentions to consume cultured proteins. Social norms influenced consumer intentions: Individuals surrounded by positive attitudes and intentions toward cultured proteins within their social networks were more inclined to want to consume these products. The predictor variables in the final model accounted for between 39% and 66% of the variance in the different cultured proteins related intentions. Understanding consumer intentions better can inform targeted communication strategies aimed at promoting the advantages of cultured proteins and facilitating its adoption., Competing Interests: Declaration of Competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study aims to describe the meat quality of young Holstein (HOL) beef-on-dairy heifers and bulls sired by Angus (ANG, n = 109), Charolais (CHA, n = 101) and Danish Blue (DBL, n = 127), and to investigate the performance of the handheld vision-based Q-FOM™ Beef camera in predicting the intramuscular fat concentration (IMF%) in M. longissimus thoracis from carcasses quartered at the 5th-6th thoracic vertebra. The results showed significant differences between crossbreeds and sexes on carcass characteristics and meat quality. DBL × HOL had the highest EUROP conformation scores, whereas ANG × HOL had darker meat with higher IMF% (3.52%) compared to CHA × HOL (2.99%) and DBL × HOL (2.51%). Bulls had higher EUROP conformation scores than heifers, and heifers had higher IMF% (3.70%) than bulls (2.31%). These findings indicate the potential for producing high-quality meat from beef-on-dairy heifers and ANG bulls. The IMF% prediction model for Q-FOM performed well with R 2  = 0.91 and root mean squared error of cross validation, RMSECV = 1.33%. The performance of the prediction model on the beef-on-dairy veal subsample ranging from 0.9 to 7.4% IMF had lower accuracy (R 2  = 0.48) and the prediction error (RMSE veal ) was 1.00%. When grouping beef-on-dairy veal carcasses into three IMF% classes (2.5% IMF bins), 62.6% of the carcasses were accurately predicted. Furthermore, Q-FOM IMF% predictions and chemically determined IMF% were similar for each combination of sex and crossbreed, revealing a potential of Q-FOM IMF% predictions to be used in breeding, when aiming for higher meat quality., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: To test potential cognitive and interpersonal moderators of two evidence-based youth depression prevention programs., Method: Two hundred four adolescents ( M age = 14.62 years, SD = 1.65; 56% female; 71% White, 11% Black, 11% multiracial, 5% Asian, 2% other races, 18% Hispanic/Latinx) were randomized to either a cognitive-behavioral (Coping With Stress [CWS]) or interpersonal (Interpersonal Psychotherapy-Adolescent Skills Training [IPT-AST]) prevention program. Potential moderators, selected based on theory and research, included rumination, negative cognitive style, dysfunctional attitudes, hopelessness, parent-adolescent conflict, negative interactions with parents and friends, and social support from parents and friends. Depression symptoms were assessed repeatedly through 18 months postintervention., Results: After adjusting for multiple comparisons, rumination ( B = -2.02, SE = .61, p = .001, d = .47), hopelessness ( B = -2.03, SE = .72, p = .005, d = .41), and conflict with father ( B = 1.68, SE = .74, p = .02, d = .32) moderated intervention effects on change in depression symptoms from postintervention through 18-month follow-up. For example, at high levels of conflict with father, youth in IPT-AST reported a significant decrease in symptoms during follow-up, whereas youth in CWS reported a nonsignificant change in symptoms. At low levels of conflict with father, youth in IPT-AST reported a significant increase in symptoms during follow-up, whereas youth in CWS reported a nonsignificant change in symptoms., Conclusions: These exploratory secondary analyses of Personalized Depression Prevention study data highlight specific cognitive and interpersonal risk factors that could be considered when determining which prevention program may be most effective for a given adolescent. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Accumulating evidence supports the presence of a general psychopathology dimension, the p factor ('p'). Despite growing interest in the p factor, questions remain about how p is assessed. Although multi-informant assessment of psychopathology is commonplace in clinical research and practice with children and adolescents, almost no research has taken a multi-informant approach to studying youth p or has examined the degree of concordance between parent and youth reports. Further, estimating p requires assessment of a large number of symptoms, resulting in high reporter burden that may not be feasible in many clinical and research settings. In the present study, we used bifactor multidimensional item response theory models to estimate parent- and adolescent-reported p in a large community sample of youth (11-17 years) and parents (N = 5,060 dyads). We examined agreement between parent and youth p scores and associations with assessor-rated youth global functioning. We also applied computerized adaptive testing (CAT) simulations to parent and youth reports to determine whether adaptive testing substantially alters agreement on p or associations with youth global functioning. Parent-youth agreement on p was moderate (r =.44) and both reports were negatively associated with youth global functioning. Notably, 7 out of 10 of the highest loading items were common across reporters. CAT reduced the average number of items administered by 57%. Agreement between CAT-derived p scores was similar to the full form (r =.40) and CAT scores were negatively correlated with youth functioning. These novel results highlight the promise and potential clinical utility of a multi-informant p factor approach., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: We sought to elicit perspectives on HIV and sexually transmitted infection (STI) prevention among adolescents with recent STIs in primary care to optimize acceptability and effectiveness in designing a novel HIV/STI prevention intervention., Methods: We enrolled 13-19 year-olds with recent gonorrhea, chlamydia, trichomonas, and/or syphilis in a multimethods cross-sectional study at two primary care clinics. Participants completed surveys and interviews. We used an integrated analytic approach deductively coding data using the Integrated Behavioral Model, then inductively coding to identify themes not represented in the Integrated Behavioral Model., Results: Participants (n = 35) were 85% cisgender female, 14% cisgender male, 1% transgender female; 25% identified as lesbian, bisexual, or queer. Most (97%) identified as non-Latinx Black. None used condoms consistently, 26% were aware of pre-exposure prophylaxis (PrEP), and 31% were never HIV tested. Five key themes emerged. 1) Mental health was central to HIV prevention behavior uptake and coping with STI diagnosis. 2) Youth desired prevention counseling that allowed decisional autonomy and individualized goal setting. 3) Negative social norms around condoms and absent norms around HIV testing and PrEP limited method uptake. 4) Both confidence and concrete skills were needed to initiate prevention methods. 5) Youth desired education at the time of STI diagnosis to improve subsequent prevention decision making., Discussion: Key intervention design considerations included 1) integrating mental health assessment and referral to services, 2) promoting individualized goal setting, 4) building communication skills, 4) providing navigation and material support for PrEP uptake and HIV testing, and 5) augmenting comprehensive STI and HIV prevention education., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To understand adolescent, parent, and provider perceptions of a machine learning algorithm for detecting adolescent suicide risk prior to its implementation primary care., Methods: We conducted semi-structured, qualitative interviews with adolescents (n = 9), parents (n = 12), and providers (n = 10; mixture of behavioral health and primary care providers) across two major health systems. Interviews were audio recorded and transcribed with analyses supported by use of NVivo. A codebook was developed combining codes derived inductively from interview transcripts and deductively from implementation science frameworks for content analysis., Results: Reactions to the algorithm were mixed. While many participants expressed privacy concerns, they believed the algorithm could be clinically useful for identifying adolescents at risk for suicide and facilitating follow-up. Parents' past experiences with their adolescents' suicidal thoughts and behaviors contributed to their openness to the algorithm. Results also aligned with several key Consolidated Framework for Implementation Research domains. For example, providers mentioned barriers inherent to the primary care setting such as time and resource constraints likely to impact algorithm implementation. Participants also cited a climate of mistrust of science and health care as potential barriers., Conclusions: Findings shed light on factors that warrant consideration to promote successful implementation of suicide predictive algorithms in pediatric primary care. By attending to perspectives of potential end users prior to the development and testing of the algorithm, we can ensure that the risk prediction methods will be well-suited to the providers who would be interacting with them and the families who could benefit., Competing Interests: Declaration of Competing Interest The authors declare there are no conflicts of interest relevant to the current manuscript. This work is funded by the National Institute of Mental Health. Authors receive additional funding from the National Institute of Mental Health and other federal granting agencies. Dr. Young receives royalties from Oxford University Press. Dr. Brent receives royalties from Guilford Press, eRT, and UpToDate and consulting fees from HealthWise. Dr. Brent also receives funding from the American Foundation for Suicide Prevention, the Beckwith Institute, and the Once Upon A Time Foundation. Dr. Melhem received an honorarium from Oakstone Publishing for providing a lecture for one of their courses., (Copyright © 2024 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Objective: Interpersonal psychotherapy (IPT) has been proposed for prevention of excess weight gain among adolescents with loss-of-control (LOC) eating. Mixed findings from a trial testing this conjecture warrant elucidation of potential outcome predictors. The therapeutic alliance (adolescent-facilitator emotional bond and task collaboration) may be important for IPT but has received little attention in weight-related interventions. This study evaluated associations of adolescent-reported therapeutic alliance during IPT with weight- and eating-related outcomes., Methods: Secondary analyses of a randomized controlled trial were conducted to compare group IPT to health education (HE) for preventing excess weight gain among 113 girls (ages 12-17) with body mass index (BMI) at the 75th to 97th percentile and LOC eating. BMI and LOC eating were measured at baseline, 12 weeks (postintervention), and 1 year. Multilevel modeling was used to test associations between change in therapeutic alliance (from session 1 to session 12) and changes in weight- and eating-related outcomes (from postintervention to 1 year). Analyses were controlled for therapeutic alliance after session 1 and for baseline and postintervention outcome values; group assignment (IPT vs. HE) was a moderator., Results: Increases in emotional bond were associated with decreased weight and with greater decreases in number of LOC eating episodes at 1 year in the IPT group (p<0.05) and with weight gain in the HE group (p<0.05). Greater task collaboration was related to greater weight gain at 1-year follow-up, regardless of group assignment (p<0.05)., Conclusions: The association of therapeutic alliance during IPT with weight and LOC eating outcomes among adolescent girls merits further investigation., Competing Interests: Dr. Crosby reports being a paid statistical consultant for Health Outcomes Solutions. Dr. Young reports receiving royalties from Oxford University Press for a book that informed the intervention reported in this article and receiving financial compensation for training and consultation on this intervention and related interventions. The other authors report no financial relationships with commercial interests.

Parental depression is a well-established risk factor for youth psychopathology; however, depression is highly heterogeneous, and different parental symptom profiles may be differentially associated with risk mechanisms and youth psychopathology outcomes. Thus, this study examined associations between parental anhedonic symptoms of depression, specifically, and (1) parenting and (2) youth outcomes using a multi-method, multi-informant approach. Participants included 595 parents (89% mothers) and youth (ages 8-16; M[SD] = 12.07[2.39]). Regression analyses indicated that parental self-reported anhedonic symptoms at baseline demonstrated relatively specific prospective associations with chronic parent-child stress assessed using contextual stress interview methods, as well as youth self-reported depressive symptoms at 18-month follow-up. Findings also indicated concurrent associations between parental anhedonic symptoms and observed parental criticism, conflict, and responsiveness in the context of a 5-min discussion task, as well as parent self-reported monitoring/supervision, although results were no longer significant after controlling for parental co-occurring non-anhedonic depressive symptoms. Findings suggest that parental anhedonic symptoms may contribute to relatively unique reductions in the quality of the parent-child relationship and may be a particularly salient risk factor for youth depression., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The goal of the current study was to document patterns of stability and change in adolescent depression and suicide risk detected via universal depression screening in pediatric primary care and to determine who may go on to experience emerging risk., Methods: Retrospective electronic health record information (sociodemographic data and depression screening results for 2 timepoints) was extracted for adolescents aged 12-17 who attended well-visits between November 15, 2017, and February 1, 2020, in a large pediatric primary care network. A total of 27,335 adolescents with 2 completed depression screeners were included in the current study., Results: While most adolescents remained at low risk for depression and suicide across the 2 timepoints, others experienced emerging risk (i.e., low risk at time 1 but elevated risk at time 2), decreasing risk (i.e., high risk at time 1 but low risk at time 2) or stable high risk for depression or suicide. Odds of experiencing emerging depression and suicide risk were higher among adolescents who were female (compared to males), Black (compared to White), and had Medicaid insurance (compared to private insurance). Odds of experiencing emerging depression risk were also higher among older adolescents (compared to younger adolescents) as well as adolescents who identified as Hispanic/Latino (compared to non-Hispanic/Latino)., Conclusions: Findings can inform symptom monitoring and opportunities for prevention in primary care., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cultivated meat is an emerging new technology to produce sustainable meat for the future. The common approach for cultivated meat, is the isolation of satellite cells from donor animals, followed by in vitro proliferation and differentiation into primitive muscle fibers. The transformation of satellite cells into myofibers is tightly orchestrated by intra-cellular signaling, while the inter-cellular signaling is less well understood. Thus, the current study was conducted to map the secretion of potential signaling molecules (MicroRNAs and proteins) during proliferation and differentiation. Primary cultures of satellite cells were grown to 50% and 80% confluence, representing the proliferative phase or serum-starved for 1 and 3 days to induce differentiation. Post incubation in FBS-free media, the media were collected and analyzed for miRNA and protein content using gene-arrays and LC-MS/MS, respectively. When comparing the miRNA secretome at 50% and 80% confluence, we observed four differentially expressed miRNA, while only five were differentially expressed when comparing Day 1 to Day 3. A subsequent in silico analysis suggested that pathways of importance for myogenesis, e.g., MAPK and AMPK signaling, could be regulated by the secreted miRNAs. In addition, >300 proteins were secreted, including insulin-like growth factor 1 binding proteins 2, 3, 4, 5 and 6. In conclusion, this study demonstrated differential secretion of several miRNAs and proteins during both proliferation and differentiation of bovine satellite cells in vitro., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jette Feveile Young reports financial support was provided by The Good Food Institute., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Unique trajectories of adolescent depression symptoms have been identified, yet less is known about whether such patterns translate to real-world clinical settings. Because annual adolescent depression screening is becoming more prevalent in primary care, we examined whether longitudinal patterns of depression symptoms documented in the developmental psychopathology literature can also be detected via routine screening in primary care and explored how membership in the identified trajectories varied based on concurrent suicide risk and sociodemographic factors. A total of 1,359 adolescents aged 12-16 years old at the first timepoint were included in the current analyses. These adolescents completed three depression screeners during their well-visits in a large pediatric primary care network between November 15, 2017 and February 1, 2020. Retrospective electronic health record data were extracted, including sociodemographic variables and depression screening results. Dynamic functional time series clustering results indicated the optimal number of clusters was five. The five depression symptom trajectories were: (1) A-Shaped (i.e., relatively low depression symptoms at Time 1, a substantial increase in symptoms at Time 2, and a return to low symptoms at Time 3), (2) Increasing, (3) Low-Stable, (4) High-Decreasing, and (5) Low-Decreasing. Cluster differences in suicide risk largely mapped onto depression symptom levels at each assessment. We found cluster differences based on practice location, insurance type, and adolescent race. The symptom trajectories observed in this study resemble those found in the developmental psychopathology literature, though some key differences were noted. Findings can inform future research and symptom monitoring in primary care., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cultivated meat production requires an efficient, robust and highly optimized serum-free cell culture media for the needed upscaling of muscle cell expansion. Existing formulations of serum-free media are complex, expensive and have not been optimized for muscle cells. Thus, we undertook this work to develop a simple and robust serum-free media for the proliferation of bovine satellite cells (SCs) through Design of Experiment (DOE) and Response Surface Methodology (RSM) using precise and high-throughput image-based cytometry. Proliferative attributes were investigated with transcriptomics and long-term performance was validated using multiple live assays. Here we formulated a media based on three highly optimized components; FGF2 (2 ng/mL), fetuin (600 µg/mL) and BSA (75 µg/mL) which together with an insulin-transferrin-selenium (1x) supplement, sustained the proliferation of bovine SCs, porcine SCs and murine C2C12 muscle cells. Remarkably, cells cultured in our media named Tri-basal 2.0+ performed better than cell cultured in 10% FBS, with respect to proliferation. Hence, the optimized Tri-basal 2.0+ enhanced serum-free cell attachment and long-term proliferation, providing an alternative solution to the use of FBS in the production of cultivated meat., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Childhood adversity places youth at risk for multiple negative outcomes. The current study aimed to understand how a constellation of risk and resilience factors influenced mental health outcomes as a function of adversities: socioeconomic status (SES) and traumatic stressful events (TSEs). Specifically, we examined outcomes related to psychosis and mood disorders, as well as global clinical functioning. The current study is a longitudinal follow up of 140 participants from the Philadelphia Neurodevelopmental Cohort (PNC) assessed for adversities at Time 1 (Mean age: 14.11 years) and risk, resilience, and clinical outcomes at Time 2 (mean age: 21.54 years). In the context of TSE, a limited set of predictors emerged as important; a more diverse set of moderators emerged in the context of SES. Across adversities, social support was a unique predictor of psychosis spectrum diagnoses and global functioning; emotion dysregulation was an important predictor for mood diagnoses. The current findings underscore the importance of understanding effects of childhood adversity on maladaptive outcomes within a resilience framework., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Adolescent mental health concerns increased during COVID-19, but it is unknown whether early increases in depression and suicide risk have been sustained. We examined changes in positive screens for depression and suicide risk in a large pediatric primary care network through May 2022., Methods: Using an observational repeated cross-sectional design, we examined changes in depression and suicide risk during the pandemic using electronic health record data from adolescents. Segmented logistic regression was used to estimate risk differences (RD) for positive depression and suicide risk screens during the early pandemic (June 2020-May 2021) and late pandemic (June 2021-May 2022) relative to before the pandemic (March 2018-February 2020). Models adjusted for seasonality and standard errors accounted for clustering by practice., Results: Among 222,668 visits for 115,627 adolescents (mean age 15.7, 50% female), the risk of positive depression and suicide risk screens increased during the early pandemic period relative to the prepandemic period (RD, 3.8%; 95% CI, 2.9, 4.8; RD, 2.8%; 95% CI, 1.7, 3.8). Risk of depression returned to baseline during the late pandemic period, while suicide risk remained slightly elevated (RD, 0.7%; 95% CI, -0.4, 1.7; RD, 1.8%; 95% CI, 0.9%, 2.7%)., Conclusions: During the early months of the pandemic, there was an increase in positive depression and suicide risk screens, which later returned to prepandemic levels for depression but not suicide risk. Results suggest that pediatricians should continue to prioritize screening adolescents for depressive symptoms and suicide risk and connect them to treatment., (Copyright © 2023 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

One Mind, in partnership with Meadows Mental Health Policy Institute, convened several virtual meetings of mental health researchers, clinicians, and other stakeholders in 2020 to identify first steps toward creating an initiative for early screening and linkage to care for youths (individuals in early adolescence through early adulthood, ages 10-24 years) with mental health difficulties, including serious mental illness, in the United States. This article synthesizes and builds on discussions from those meetings by outlining and recommending potential steps and considerations for the development and integration of a novel measurement-based screening process in youth-facing school and medical settings to increase early identification of mental health needs and linkage to evidence-based care. Meeting attendees agreed on an initiative incorporating a staged assessment process that includes a first-stage brief screener for several domains of psychopathology. Individuals who meet threshold criteria on the first-stage screener would then complete an interview, a second-stage in-depth screening, or both. Screening must be followed by recommendations and linkage to an appropriate level of evidence-based care based on acuity of symptoms endorsed during the staged assessment. Meeting attendees proposed steps and discussed additional considerations for creating the first nationwide initiative for screening and linkage to care, an initiative that could transform access of youths to mental health screening and care., Competing Interests: Ms. McGough has served as a conference adviser and board member for Janssen Pharmaceuticals, as an advocacy board member for Alkermes, and as a social media awareness campaign participant for Teva Pharmaceuticals. Dr. Niendam is the founder and a board member of Safari Health Inc. Mr. Staglin is a Mindstrong Health board member. Dr. Young receives royalties from Oxford University Press. Dr. Bearden is on the Novartis Neuroscience Scientific Advisory Board and the One Mind Scientific Advisory Board. The other authors report no financial relationships with commercial interests.

Stress is one candidate mechanism posited to contribute to the intergenerational risk of psychopathology. However, the ways in which parent and child stress are related across adolescence, and the role that co-occurring parent and child stress may exert regarding bidirectional risk for internalizing symptoms, are not well understood. Using repeated measures data spanning 3-years, this study investigated (1) the extent to which trajectories of parent and child stress are related during adolescence, and (2) whether co-occurring parent and child stress trajectories mediate prospective, bidirectional associations between parent depression symptoms and child internalizing symptoms (depression, physical and social anxiety). Participants included 618 parent-adolescent dyads (age 8-16; 57% girls; 89% mothers). Parent depressive symptoms and child symptoms of depression, social anxiety, and physical anxiety were assessed via self-report questionnaire at baseline and 36 months later. Parent and child stress were assessed via self-report questionnaire every three months between 3- and 33-months (11 total assessments). Latent growth curve model (LGCM) analysis found that parent and child stress trajectories were positively related across development. Prospective LGCM mediation analysis showed that higher youth stress at 3-months partially mediated prospective relations between parental depressive symptoms at baseline and youth depressive, as well as physical and social anxiety symptoms at 36-months. Parent and child stress reinforce each other across adolescence and may lead to increased risk for psychopathology. Increases in child stress represent an important factor conferring transdiagnostic risk for internalizing among children of depressed parents., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: We identified common and unique barriers and facilitators of evidence-based suicide prevention practices across primary care practices with integrated behavioral health services and specialty mental health settings to identify generalizable strategies for enhancing future implementation efforts., Method: Twenty-six clinicians and practice leaders from behavioral health ( n  = 2 programs) and primary care ( n  = 4 clinics) settings participated. Participation included a semi-structured qualitative interview on barriers and facilitators to implementing evidence-based suicide prevention practices. Within that interview, clinicians participated in a chart-stimulated recall exercise to gather additional information about decision making regarding suicide screening. Interview guides and qualitative coding were informed by leading frameworks in implementation science and behavioral science, and an integrated approach to interpreting qualitative results was used., Results: There were a number of similar themes associated with implementation of suicide prevention practices across settings and clinician types, such as the benefits of inter-professional collaboration and uncertainties about managing suicidality once risk was disclosed. Clinicians also highlighted barriers unique to their settings. For primary care settings, time constraints and competing demands were consistently described as barriers. For specialty mental health settings, difficulties coordinating care with schools and other providers in the community made implementation of suicide prevention practices challenging., Conclusion: Findings can inform the development and testing of implementation strategies that are generalizable across primary care and specialty mental health settings, as well as those tailored for unique site needs, to enhance use of evidence-based suicide prevention practices in settings where individuals at risk for suicide are especially likely to present.HIGHLIGHTSWe examined barriers and facilitators to suicide prevention across health settings.Common and unique barriers and facilitators across health-care settings emerged.Findings can enhance suicide prevention implementation across health-care settings.

Objective: Depression and stressors both increase during adolescence. The stress generation model posits that depression symptoms and associated impairment contribute to the generation of dependent stressors. Adolescent depression prevention programs have been shown to reduce the risk of depression. Recently, risk-informed personalization approaches have been adopted to enhance the efficacy of depression prevention, and preliminary evidence supports the beneficial effects of personalized prevention on depression symptoms. Given the close association between depression and stress, we examined the hypothesis that personalized depression prevention programs would reduce adolescents' experience of dependent stressors (interpersonal and non-interpersonal) over longitudinal follow-up., Method: The present study included 204 adolescents (56% girls, 29% racial minority) who were randomized to receive either a cognitive-behavioral or an interpersonal prevention program. Youth were categorized as high or low on cognitive and interpersonal risk using a previously established risk classification system. Half of the adolescents received a prevention program that matched their risk profile (e.g., high cognitive risk randomized to cognitive-behavioral prevention); half received a mismatched program (e.g., high interpersonal risk randomized to cognitive-behavioral prevention). Exposure to dependent and independent stressors was assessed repeatedly over an 18-month follow-up period., Results: Matched adolescents reported fewer dependent stressors during the post-intervention follow-up period ( d = .46, p = .002) and from baseline through 18-months post-intervention ( d = .35, p = .02) compared to mismatched youth. As expected, there were no differences between matched and mismatched youth on the experience of independent stressors., Conclusions: These findings further highlight the potential of personalized approaches to depression prevention and demonstrate benefits that go beyond depression symptom reduction.

This study evaluated the fidelity, feasibility, acceptability, and preliminary outcomes of a depression prevention program, interpersonal psychotherapy-adolescent skills training (IPT-AST), in urban pediatric primary care (PC) with a sample of primarily Black youth. Twenty-two adolescents with elevated depressive symptoms participated in this open clinical trial. Adolescents were identified through a screening questionnaire completed at well visits. Ratings of IPT-AST fidelity and session attendance were recorded. Youth and caregivers reported on their attitudes toward the intervention and completed measures of adolescents' symptoms and functioning pre- and post-intervention. Results demonstrated high levels of fidelity, attendance, and acceptability, despite some difficulties with recruitment. Adolescents and caregivers reported significant improvements in functioning. There were marginally significant reductions in self-reported depression, anxiety, and total mental health symptoms. Caregivers reported a significant decrease in total mental health symptoms. Findings provide preliminary information regarding the implementation and effects of IPT-AST when delivered in PC., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Interpersonal Psychotherapy-Adolescent Skills Training (IPT-AST) is an evidence-based indicated depression prevention program that has been shown to reduce depression symptoms. Research is needed to identify moderators of IPT-AST's effects. Although trauma history has emerged as a moderator of depression treatment outcomes, the impact of trauma on short- and long-term outcomes in the context of preventive interventions for adolescent depression is unknown. This study examines the impact of trauma on prevention outcomes in a school-based randomized controlled trial (RCT) in which 186 adolescents (mean age = 14.01 years, SD = 1.22; 67% female) were randomly assigned to IPT-AST delivered by research staff or group counseling (GC) provided by school counselors. Trauma history significantly moderated intervention outcomes during the active phase of the intervention, but not during long-term follow-up. During the active phase, youth in IPT-AST with low or no trauma exposure experienced significantly greater reductions in depression symptoms than youth in GC with low or no trauma exposure, but there were no significant differences in rates of change between the two interventions for youth with high or any trauma exposure. These findings highlight the importance of assessing trauma and investigating whether these interventions can be tailored or supplemented to enhance the effects for youth with trauma exposure., Competing Interests: Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Promoting Resilience in Stress Management (PRISM) is a well-established resilience coaching program for youth with chronic illness. It is a one-on-one intervention targeting skills in stress management, goal-setting, cognitive reframing, and meaning-making. We aimed to (i) assess the feasibility and acceptability of PRISM and (ii) explore PRISM's impact on clinical outcomes among youth with chronic musculoskeletal pain (CMP). This was a single-arm pilot trial of PRISM for youth with CMP aged 12-17 years. Patients completed patient-reported outcome measures (PROs) pre- and post- intervention; patients and caregivers provided qualitative feedback. Twenty-seven patients were enrolled (63% enrollment rate); 82% percent were female. The patients' median age was 16 years (IQR: 13-16). The intervention completion rate was 81% ( n = 22). The mean satisfaction for PRISM overall was 4.3 (SD 0.9), while the mean acceptability of the intervention measure (AIM) was 4.4 (SD 0.89). Participants reported improved resilience (2.2 [SD 5.1]), functional disability (-3.5 [IQR: -6.0, 1.0]), and psychological distress (-1.0 [-5.0, 2.0]) from baseline to immediately post-treatment; pain intensity, pain catastrophizing, and global health were similar at both time points. Feedback was positive and suggested that a group component may be helpful. PRISM is feasible and acceptable among youth with CMP. Exploratory analyses suggest improvements in clinically relevant outcomes, warranting further investigation.

Culturing eukaryotic cells has widespread applications in research and industry, including the emerging field of cell-cultured meat production colloquially referred to as "cellular agriculture". These applications are often restricted by the high cost of growth medium necessary for cell growth. Mitogenic protein growth factors (GFs) are essential components of growth medium and account for upwards of 90% of the total costs. Here, we present a set of expression constructs and a simplified protocol for recombinant production of functionally active GFs, including FGF2, IGF1, PDGF-BB, and TGF-β1 in Escherichia coli . Using this E. coli expression system, we produced soluble GF orthologs from species including bovine, chicken, and salmon. Bioactivity analysis revealed orthologs with improved performance compared to commercially available alternatives. We estimated that the production cost of GFs using our methodology will significantly reduce the cost of cell culture medium, facilitating low-cost protocols tailored for cultured meat production and tissue engineering., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)