Translation, cultural adaptation and validation of Patient Health Questionnaire and generalized anxiety disorder among adolescents in Nepal.

BACKGROUND: Depression and anxiety are significant contributors to the global burden of disease among young people. Accurate data on the prevalence of these conditions are crucial for the equitable distribution of resources for planning and implementing effective programs. This study aimed to culturally adapt and validate data collection tools for measuring depression and anxiety at the population level. METHODS: The study was conducted in Kathmandu, Nepal, a diverse city with multiple ethnicities, languages, and cultures. Ten focus group discussions with 56 participants and 25 cognitive interviews were conducted to inform adaptations of the Patient Health Questionnaire adapted for Adolescents (PHQ-A) and Generalized Anxiety Disorder (GAD-7). To validate the tools, a cross-sectional survey of 413 adolescents (aged 12-19) was conducted in three municipalities of Kathmandu district. Trained clinical psychologists administered the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-DSM 5 version) to survey participants. RESULTS: A number of cultural adaptations were required, such as changing statements into questions, using a visual scale (glass scale) to maintain uniformity in responses, and including a time frame at the beginning of each item. For younger adolescents aged 12 to 14 years, a PHQ-A cut-off of > = 13 had a sensitivity of 0.93, specificity of 0.80, positive predictive value (PPV) of 0.33, and negative predictive value (NPV) of 0.99. For older adolescents aged 15-19, a cut-off of > = 11 had a sensitivity of 0.89, specificity of 0.70, PPV of 0.32, and NPV of 0.97. For GAD-7, a cut-off of > = 8 had a sensitivity of 0.70 and specificity of 0.67 for younger adolescents and 0.71 for older adolescents, with a PPV of 0.39 and NPV of 0.89. The individual symptom means of both PHQ-A and GAD-7 items showed moderate ability to discriminate between adolescents with and without depression and anxiety. CONCLUSION: The PHQ-A and GAD-7 demonstrate fair psychometric properties for screening depression but performed poorly for anxiety, with high rates of false positives. Even when using clinically validated cut-offs, population prevalence rates would be inflated by 2-4 fold with these tools, requiring adjustment when interpreting epidemiological findings.

Development of a school-based programme for mental health promotion and prevention among adolescents in Nepal and South Africa.

Introduction: Adolescence is a critical time for mental health promotion and prevention and establishing healthy behaviours. Implementing universal, school-based psychosocial interventions can improve short- and long-term health trajectories for adolescents. While these interventions may offer important opportunities for fostering skills and relationships, few school-based interventions have been developed for and tested in low- and middle-income countries (LMICs) where adolescent mental health needs may be significant and under-served. This manuscript details the development of a multi-component, universal school-based intervention, Health Action in ScHools for a Thriving Adolescent Generation (HASHTAG), for adolescents aged 12-15 years in Nepal and South Africa. Methods and results: We describe HASHTAG's development over four phases, combining methods and results as each phase was iteratively conducted between 2018 and 2021. Phase 1 included a systematic review and components analysis, building from WHO guidelines for adolescent mental health. Seven components were strongly supported by the evidence: emotional regulation, stress management, mindfulness, problem-solving, interpersonal skills, assertiveness training, and alcohol and drug education. Phase 2 encompassed site selection, theory of change development, and formative research engagements; research teams in each site engaged adolescents and key adult stakeholders to identify priorities for intervention. Stakeholders voiced preferences for external facilitators and key content and delivery for intervention sessions. These findings informed Phase 3, a draft manual of HASHTAG, including a whole-school component, called Thriving Environment in Schools, and a classroom-based, six-session component, Thrive Together. In Phase 4, participants engaged in consultative workshops to review and contextualise content by country, preparing HASHTAG for implementation in a feasibility trial. Minor adaptations were made in Nepal, including using school nurses and adjusting take-home materials; both country's workshops identified practical considerations for implementing activities. Conclusions: HASHTAG was designed around core evidence-based components to increase translatability across LMICs, while enabling country-specific tailoring to enhance feasibility. Future research will test whether this multi-component, whole-school approach can improve adolescent mental health.

Prevalence of depression and associated symptoms among patients attending primary healthcare facilities: a cross-sectional study in Nepal.

BACKGROUND: Depression is a prevalent mental health condition worldwide but there is limited data on its presentation and associated symptoms in primary care settings in low- and middle-income countries like Nepal. This study aims to assess the prevalence of depression, its hallmark and other associated symptoms that meet the Diagnostic and Statistical Manual (DSM-5) criteria in primary healthcare facilities in Nepal. The collected information will be used to determine the content of a mobile app-based clinical guidelines for better detection and management of depression in primary care. METHODS: A total of 1,897 adult patients aged 18-91 (63.1% women) attending ten primary healthcare facilities in Jhapa, a district in eastern Nepal, were recruited for the study between August 2, 2021, and March 25, 2022. Trained research assistants conducted face-to-face interviews in private spaces before the consultation with healthcare providers. Depression symptoms, including hallmark symptoms, was assessed using the validated Nepali version of the Patient Health Questionnaire (PHQ-9). RESULTS: One in seven (14.5%) individuals attending primary health care facilities in Jhapa met the threshold for depression based on a validated cut-off score ( > = 10) on the PHQ-9. The most commonly reported depressive symptoms were loss of energy and sleep difficulties. Approximately 25.4% of women and 18.9% of men endorsed at least one of the two hallmark symptoms on the PHQ-9. Using a DSM-5 algorithm (at least one hallmark symptom and five or more total symptoms) to score the PHQ-9, 6.3% of women and 4.3% of men met the criteria for depression. The intra-class correlation coefficient for PHQ-9 total scores by health facility as the unit of clustering was 0.01 (95% confidence interval, 0.00-0.04). CONCLUSION: Depression symptoms are common among people attending primary healthcare facilities in Nepal. However, the most common symptoms are not the two hallmark criteria. Use of total scores on a screening tool such as the PHQ-9 risks overestimating the prevalence and generating false positive diagnoses. Compared to using cut off scores on screening tools, training health workers to first screen for hallmark criteria may increase the accuracy of identification and lead to better allocation of treatment resources.

Effectiveness of combining prevention psychological interventions with interventions that address the social determinants of mental health in low and middle-income countries: protocol of a systematic review and meta-analysis.

INTRODUCTION: Common mental health conditions (CMHCs), including depression, anxiety and post-traumatic stress disorder (PTSD), are highly prevalent in low and middle-income countries (LMICs). Preventive strategies combining psychological interventions with interventions addressing the social determinants of mental health may represent a key strategy for effectively preventing CMHCs. However, no systematic reviews have evaluated the effectiveness of these combined intervention strategies for preventing CMHCs. METHODS AND ANALYSIS: This systematic review will include randomised controlled trials (RCTs) focused on the effectiveness of interventions that combine preventive psychological interventions with interventions that address the social determinants of mental health in LMICs. Primary outcome is the frequency of depression, anxiety or PTSD at postintervention as determined by a formal diagnostic tool or any other standardised criteria. We will search Epistemonikos, Cochrane Controlled Trials Register (CENTRAL), MEDLINE, Embase, PsycINFO, CINAHL, Global Index Medicus, ClinicalTrials.gov (Ctgov), International Clinical Trials Registry Platform (ICTRP). Two reviewers will independently extract the data and evaluate the risk of bias of included studies using the Cochrane risk of bias tool 2. Random-effects meta-analyses will be performed, and certainty of evidence will be rated using the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: This study uses data from published studies; therefore, ethical review is not required. Findings will be presented in a published manuscript. TRIAL REGISTRATION NUMBER: CRD42023451072.

Strengthening self-regulation and reducing poverty to prevent adolescent depression and anxiety: Rationale, approach and methods of the ALIVE interdisciplinary research collaboration in Colombia, Nepal and South Africa.

AIMS: Depression and anxiety are the leading contributors to the global burden of disease among young people, accounting for over a third (34.8%) of years lived with disability. Yet there is limited evidence for interventions that prevent adolescent depression and anxiety in low- and middle-income countries (LMICs), where 90% of adolescents live. This article introduces the 'Improving Adolescent mentaL health by reducing the Impact of poVErty (ALIVE)' study, its conceptual framework, objectives, methods and expected outcomes. The aim of the ALIVE study is to develop and pilot-test an intervention that combines poverty reduction with strengthening self-regulation to prevent depression and anxiety among adolescents living in urban poverty in Colombia, Nepal and South Africa. METHODS: This aim will be achieved by addressing four objectives: (1) develop a conceptual framework that identifies the causal mechanisms linking poverty, self-regulation and depression and anxiety; (2) develop a multi-component selective prevention intervention targeting self-regulation and poverty among adolescents at high risk of developing depression or anxiety; (3) adapt and validate instruments to measure incidence of depression and anxiety, mediators and implementation parameters of the prevention intervention; and (4) undertake a four-arm pilot cluster randomised controlled trial to assess the feasibility, acceptability and cost of the selective prevention intervention in the three study sites. RESULTS: The contributions of this study include the active engagement and participation of adolescents in the research process; a focus on the causal mechanisms of the intervention; building an evidence base for prevention interventions in LMICs; and the use of an interdisciplinary approach. CONCLUSIONS: By developing and evaluating an intervention that addresses multidimensional poverty and self-regulation, ALIVE can make contributions to evidence on the integration of mental health into broader development policy and practice.

Experience of primary healthcare workers in using the mobile app-based WHO mhGAP intervention guide in detection and treatment of people with mental disorders: A qualitative study in Nepal.

This study assessed perception and experience of trained primary health care workers in using a mobile app-based version of the WHO mental health gap action programme (mhGAP) Intervention Guide in the assessment and management of people with mental health conditions in primary care in Nepal. A qualitative study was conducted with primary healthcare workers who were trained in using the WHO mhGAP mobile application in Jhapa, a district in eastern Nepal. Semi-structured interviews were carried out with 15 healthcare workers (3 females and 12 males) nine months after the training. Interviews were audio recorded, transcribed and translated into English for the thematic qualitative data analysis. Health care workers (HCWs) found the mobile app helpful to verify and confirm their assessment and diagnosis. The other benefits reported by the participants were: bringing uniformity in diagnosis and management of mental health conditions across primary healthcare facilities; reminding the HCWs specific assessment questions; creating awareness on the importance of psychosocial intervention; improving the interaction between patients and service providers; and the importance of follow-up care. Despite these advantages, lack of clarity about report submission modality; lack of electricity or internet connectivity; and low technology literacy among older HCWs were some of the barriers in using the app. The major recommendation made by the HCWs for the guide included revision of the assessment process and system; inclusion of a chat function with supervisors; minimizing the amount of patients' data to be collected in the app; and addition of conversion and anxiety disorders to the app. This study concludes that the mobile decision support application could be acceptable and feasible in primary care settings if the suggested modifications are incorporated, in addition to addressing other systemic issues facing the primary care-based delivery of mental health services.

A mixed methods evaluation of a World Health Organization competency-based training package for foundational helping skills among pre-service and in-service health workers in Nepal, Peru and Uganda.

Health systems globally demand more competent workers but lack competency-based training programs to reach their goals. This study evaluates the effectiveness of a competency-based curriculum (EQUIP-FHS) for trainers and supervisors to teach foundational helping knowledge, attitudes and skills, guided by the WHO/UNICEF EQUIP platform, to improve the competency of in-service and pre-service workers from various health and other service sectors. A mixed-methods, uncontrolled before-and-after trial was conducted in Nepal, Peru, and Uganda from 2020 to 2021. Trainees' (N = 150) competency data were collected during 13 FHS trainings. Paired t-tests assessed pre- to post-change in ENACT competency measures (e.g., harmful, helpful). Qualitative data was analyzed using thematic analysis. EQUIP-FHS trainings, on average, were 20 h in duration. Harmful behaviors significantly decreased, and helpful behaviors significantly increased, across and within sites from pre-to post-training. Qualitatively, trainees and trainers promoted the training and highlighted difficult competencies and areas for scaling the training. A brief competency-based curriculum on foundational helping delivered through pre-service or in-service training can reduce the risk that healthcare workers and other service providers display harmful behaviors. We recommend governmental and nongovernmental organizations implement competency-based approaches to enhance the quality of their existing workforce programming and be one step closer to achieving the goal of quality healthcare around the globe.

The burden of mental disorders in Nepal between 1990 and 2019: Findings from the Global Burden of Disease Study 2019.

Mental disorders are the leading cause of disease burden, affecting 13% of all people globally in 2019. However, there is scarce evidence on the burden of mental disorders in Nepal. This study used the Global Burden of Disease Study 2019 data to assess the prevalence and disability-adjusted life-years (DALYs) of mental disorders in Nepal between 1990 and 2019. In 2019, there were 3.9 million (95% UI: 3.6-4.3) people with mental disorders in Nepal. Major depressive disorders (1.1 million; 95% UI: 0.9-1.2 million) and anxiety disorders (0.9 million; 95% UI: 0.8-1.2 million) were the most prevalent mental disorders in 2019. Attention deficit hyperactive disorder, conduct disorder, and autism spectrum disorders were present twice as high in males than in females. The proportional contribution of mental disorders to the total disease burden has tripled between 1990 (1.79% of all DALYs) and 2019 (5.5% of all DALYs). In conclusion, the proportional contribution of mental disorders to total disease burden has increased significantly in the last three decades in Nepal, with apparent sex and age differentials in prevalence and DALY rates. Effective program and policy responses are required to prepare the health system for reducing the growing burden of mental health disorders in Nepal.

Development and testing the feasibility of a sports-based mental health promotion intervention in Nepal: a protocol for a pilot cluster-randomised controlled trial.

BACKGROUND: Mental wellbeing encompasses life satisfaction, social connectedness, agency and resilience. In adolescence, mental wellbeing reduces sexual health risk behaviours, substance use and violence; improves educational outcomes; and protects mental health in adulthood. Mental health promotion seeks to improve mental wellbeing and can include activities to engage participants in sport. However, few high-quality trials of mental health promotion interventions have been conducted with adolescents, especially in low- and middle-income countries. We sought to address this gap by testing SMART (Sports-based Mental heAlth pRomotion for adolescenTs) in a pilot cluster-randomised controlled trial (cRCT) in Bardiya, Nepal. METHODS: The objectives of the trial are to assess the acceptability and feasibility of SMART, test trial procedures, explore outcome distributions in intervention and control clusters and calculate the total annual cost of the intervention and unit cost per adolescent. The trial design is a parallel-group, two-arm superiority pilot cRCT with a 1:1 allocation ratio and two cross-sectional census surveys with adolescents aged 12-19, one pre-intervention (baseline) and one post-intervention (endline). The study area is four communities of approximately 1000 population (166 adolescents per community). Each community represents one cluster. SMART comprises twice weekly football, martial arts and dance coaching, open to all adolescents in the community, led by local sports coaches who have received psychosocial training. Sports melas (festivals) and theatre performances will raise community awareness about SMART, mental health and the benefits of sport. Adolescents in control clusters will participate in sport as usual. In baseline and endline surveys, we will measure mental wellbeing, self-esteem, self-efficacy, emotion regulation, social support, depression, anxiety and functional impairment. Using observation checklists, unstructured observation and attendance registers from coaching sessions, and minutes of meetings between coaches and supervisors, we will assess intervention fidelity, exposure and reach. In focus group discussions and interviews with coaches, teachers, caregivers and adolescents, we will explore intervention acceptability and mechanisms of change. Intervention costs will be captured from monthly project accounts, timesheets and discussions with staff members. DISCUSSION: Findings will identify elements of the intervention and trial procedures requiring revision prior to a full cRCT to evaluate the effectiveness of SMART. TRIAL REGISTRATION: ISRCTN, ISRCTN15973986 , registered on 6 September 2022; ClinicalTrials.gov, NCT05394311 , registered 27 May 2022.

Adipogenic and SWAT cells separate from a common progenitor in human brown and white adipose depots.

Adipocyte function is a major determinant of metabolic disease, warranting investigations of regulating mechanisms. We show at single-cell resolution that progenitor cells from four human brown and white adipose depots separate into two main cell fates, an adipogenic and a structural branch, developing from a common progenitor. The adipogenic gene signature contains mitochondrial activity genes, and associates with genome-wide association study traits for fat distribution. Based on an extracellular matrix and developmental gene signature, we name the structural branch of cells structural Wnt-regulated adipose tissue-resident (SWAT) cells. When stripped from adipogenic cells, SWAT cells display a multipotent phenotype by reverting towards progenitor state or differentiating into new adipogenic cells, dependent on media. Label transfer algorithms recapitulate the cell types in human adipose tissue datasets. In conclusion, we provide a differentiation map of human adipocytes and define the multipotent SWAT cell, providing a new perspective on adipose tissue regulation.

Practitioners' perspectives on preparing for and delivering remote psychological support in Nepal, Perú and the United States during COVID-19.

INTRODUCTION: The COVID-19 pandemic has propelled a global paradigm shift in how psychological support is delivered. Remote delivery, through phone and video calls, is now commonplace around the world. However, most adoption of remote delivery methods is occurring without any formal training to ensure safe and effective care. OBJECTIVE: The purpose of this applied qualitative study was to determine practitioners' experiences of rapidly adapting to deliver psychological support remotely during COVID-19. DESIGN: We used a pragmatic paradigm and applied approach to gain perspectives related to the feasibility and perceived usefulness of synchronous remote psychological support, including views on how practitioners can be prepared. METHODS: Key informant interviews were conducted remotely with 27 specialist and non-specialist practitioners in Nepal, Perú and the USA. Interviewees were identified through purposeful sampling. Data were analysed using framework analysis. RESULTS: Respondents revealed three key themes: (i) Remote delivery of psychological support raises unique safety concerns and interference with care, (ii) Remote delivery enhances skills and expands opportunities for delivery of psychological support to new populations, and (iii) New training approaches are needed to prepare specialist and non-specialist practitioners to deliver psychological support remotely. CONCLUSIONS: Remote psychological support is feasible and useful for practitioners, including non-specialists, in diverse global settings. Simulated remote role plays may be a scalable method for ensuring competency in safe and effective remotely-delivered care.

Optimizing Levilactobacillus brevis NPS-QW 145 Fermentation for Gamma-Aminobutyric Acid (GABA) Production in Soybean Sprout Yogurt-like Product.

Gamma-aminobutyric acid (GABA) is a non-protein amino acid with various physiological functions. Levilactobacillus brevis NPS-QW 145 strains active in GABA catabolism and anabolism can be used as a microbial platform for GABA production. Soybean sprouts can be treated as a fermentation substrate for making functional products. This study demonstrated the benefits of using soybean sprouts as a medium to produce GABA by Levilactobacillus brevis NPS-QW 145 when monosodium glutamate (MSG) is the substrate. Based on this method, a GABA yield of up to 2.302 g L-1 was obtained with a soybean germination time of one day and fermentation of 48 h with bacteria using 10 g L-1 glucose according to the response surface methodology. Research revealed a powerful technique for producing GABA by fermentation with Levilactobacillus brevis NPS-QW 145 in foods and is expected to be widely used as a nutritional supplement for consumers.

Mycobacterium tuberculosis Requires the Outer Membrane Lipid Phthiocerol Dimycocerosate for Starvation-Induced Antibiotic Tolerance.

Tolerance of Mycobacterium tuberculosis to antibiotics contributes to the long duration of tuberculosis (TB) treatment and the emergence of drug-resistant strains. M. tuberculosis drug tolerance is induced by nutrient restriction, but the genetic determinants that promote antibiotic tolerance triggered by nutrient limitation have not been comprehensively identified. Here, we show that M. tuberculosis requires production of the outer membrane lipid phthiocerol dimycocerosate (PDIM) to tolerate antibiotics under nutrient-limited conditions. We developed an arrayed transposon (Tn) mutant library in M. tuberculosis Erdman and used orthogonal pooling and transposon sequencing (Tn-seq) to map the locations of individual mutants in the library. We screened a subset of the library (~1,000 mutants) by Tn-seq and identified 32 and 102 Tn mutants with altered tolerance to antibiotics under stationary-phase and phosphate-starved conditions, respectively. Two mutants recovered from the arrayed library, ppgK::Tn and clpS::Tn, showed increased susceptibility to two different drug combinations under both nutrient-limited conditions, but their phenotypes were not complemented by the Tn-disrupted gene. Whole-genome sequencing revealed single nucleotide polymorphisms in both the ppgK::Tn and clpS::Tn mutants that prevented PDIM production. Complementation of the clpS::Tn ppsD Q291* mutant with ppsD restored PDIM production and antibiotic tolerance, demonstrating that loss of PDIM sensitized M. tuberculosis to antibiotics. Our data suggest that drugs targeting production of PDIM, a critical M. tuberculosis virulence determinant, have the potential to enhance the efficacy of existing antibiotics, thereby shortening TB treatment and limiting development of drug resistance. IMPORTANCE Mycobacterium tuberculosis causes 10 million cases of active TB disease and over 1 million deaths worldwide each year. TB treatment is complex, requiring at least 6 months of therapy with a combination of antibiotics. One factor that contributes to the length of TB treatment is M. tuberculosis phenotypic antibiotic tolerance, which allows the bacteria to survive prolonged drug exposure even in the absence of genetic mutations causing drug resistance. Here, we report a genetic screen to identify M. tuberculosis genes that promote drug tolerance during nutrient starvation. Our study revealed the outer membrane lipid phthiocerol dimycocerosate (PDIM) as a key determinant of M. tuberculosis antibiotic tolerance triggered by nutrient starvation. Our study implicates PDIM synthesis as a potential target for development of new TB drugs that would sensitize M. tuberculosis to existing antibiotics to shorten TB treatment.

Understanding Nepali widows' experiences for the adaptation of an instrument to assess Prolonged Grief Disorder.

The experience of grief varies across different cultures and contexts. Women in Nepal who lose their husbands confront discrimination, social isolation, and abuse that influence their experience of grief. Through eight focus group discussions with Nepali widows, we elicited socially sanctioned grief reactions and local idioms used to describe common cognitive, behavioral, and emotional symptoms of grief. Accordingly, modifications to an existing instrument for Prolonged Grief Disorder, the PG-13, are suggested to capture grief symptoms as experienced by Nepali widows. Items in the PG-13 were translated to colloquial Nepali and adapted to maintain comprehensibility, acceptability, relevance, and completeness. Based on the grief-related issues reported in the focus group discussions, the addition of five new items and a new criterion to capture symptoms related to social discrimination are proposed. Widows perceived elevated symptoms one year after the loss to be problematic. It is thus recommended that the duration criterion in the original PG-13 be adjusted from at least six months to at least one year after the loss. These proposed modifications to the instrument should be validated through future psychometric testing.

Measurement of Mental Health Among Adolescents at the Population Level: A Multicountry Protocol for Adaptation and Validation of Mental Health Measures.

PURPOSE: Mental disorders are among the leading causes of disability among adolescents aged 10-19 years. However, data on prevalence of mental health conditions are extremely sparse across low- and middle-income countries, even though most adolescents live in these settings. This data gap is further exacerbated because few brief instruments for adolescent mental health are validated in these settings, making population-level measurement of adolescent mental health especially cumbersome to carry out. In response, the UNICEF has undertaken the Measurement of Mental Health Among Adolescents at the Population Level (MMAP) initiative, validating open-access brief measures and encouraging data collection in this area. METHODS: This protocol presents the MMAP mixed-methods approach for cultural adaptation and clinical validation of adolescent mental health data collection tools across settings. Qualitative activities include an initial translation and adaptation, review by mental health experts, focus-group discussions with adolescents, cognitive interviews, synthesis of findings, and back-translation. An enriched sample of adolescents with mental health problems is then interviewed with the adapted tool, followed by gold-standard semistructured diagnostic interviews. RESULTS: The study protocol is being implemented in Belize, Kenya, Nepal, and South Africa and includes measures for anxiety, depression, functional limitations, suicidality, care-seeking, and connectedness. Analyses, including psychometrics, will be conducted individually by country and combined across settings to assess the MMAP methodological process. DISCUSSION: This protocol contributes to closing the data gap on adolescent mental health conditions by providing a rigorous process of cross-cultural adaptation and validation of data collection approaches.

Development and functioning of the mobile app-based mh-GAP intervention guide in detection and treatment of people with mental health conditions in primary healthcare settings in Nepal.

This paper describes the development process of a mobile app-based version of the World Health Organization mental health Gap Action Programme Intervention Guide, testing of the app prototypes, and its functionality in the assessment and management of people with mental health conditions in Nepal. Health workers' perception of feasibility and acceptability of using mobile technology in mental health care was assessed during the inspiration phase (N = 43); the ideation phase involved the creation of prototypes; and prototype testing was conducted over multiple rounds with 15 healthcare providers. The app provides provisional diagnoses and treatment options based on reported symptoms. Participants found the app prototype useful in reminding them of the process of assessment and management of mental disorders. Some challenges were noted, these included a slow app prototype with multiple technical problems, including difficulty in navigating 'yes'/'no' options, and there were challenges reviewing detailed symptoms of a particular disorder using a "more information" icon. The initial feasibility work suggests that if the technical issues are addressed, the e-mhGAP warrants further research to understand if it is a useful method in improving the detection of people with mental health conditions and initiation of evidence-based treatment in primary healthcare facilities.

Healthcare use and costs among individuals receiving mental health services for depression within primary care in Nepal.

BACKGROUND: Integrating mental health services into primary care is a key strategy for reducing the mental healthcare treatment gap in low- and middle-income countries. We examined healthcare use and costs over time among individuals with depression and subclinical depressive symptoms in Chitwan, Nepal to understand the impact of integrated care on individual and health system resources. METHODS: Individuals diagnosed with depression at ten primary care facilities were randomized to receive a package of integrated care based on the Mental Health Gap Action Programme (treatment group; TG) or this package plus individual psychotherapy (TG + P); individuals with subclinical depressive symptoms received primary care as usual (UC). Primary outcomes were changes in use and health system costs of outpatient healthcare at 3- and 12-month follow up. Secondary outcomes examined use and costs by type. We used Poisson and log-linear models for use and costs, respectively, with an interaction term between time point and study group, and with TG as reference. RESULTS: The study included 192 primary care service users (TG = 60, TG + P = 60, UC = 72; 86% female, 24% formally employed, mean age 41.1). At baseline, outpatient visits were similar (- 11%, p = 0.51) among TG + P and lower (- 35%, p = 0.01) among UC compared to TG. Visits increased 2.30 times (p < 0.001) at 3 months among TG, with a 50% greater increase (p = 0.03) among TG + P, before returning to baseline levels among all groups at 12 months. Comparing TG + P to TG, costs were similar at baseline (- 1%, p = 0.97) and cost changes did not significantly differ at three (- 16%, p = 0.67) or 12 months (- 45%, p = 0.13). Costs among UC were 54% lower than TG at baseline (p = 0.005), with no significant differences in cost changes over follow up. Post hoc analysis indicated individuals not receiving psychotherapy used less frequent, more costly healthcare. CONCLUSION: Delivering psychotherapy within integrated services for depression resulted in greater healthcare use without significantly greater costs to the health system or individual. Previous research in Chitwan demonstrated psychotherapy determined treatment effectiveness for people with depression. While additional research is needed into service implementation costs, our findings provide further evidence supporting the inclusion of psychotherapy within mental healthcare integration in Nepal and similar contexts.

Social determinants of impaired functioning among Nepali widows: A mixed methods study.

Despite considerable stigmatisation of widows in Nepal, little is known about factors affecting their ability to function in society. Using mixed methods, we studied psychosocial factors associated with impaired functioning among Nepali widows. For the qualitative analysis, we analysed 3 focus groups, 25 in-depth interviews, and 12 key-informant interviews. The quantitative analysis was based on data from 204 widows. Odds ratios were calculated linking psychosocial exposures to impaired functioning using adjusted logistic regression models. Low social support (aOR = 2.35, 95% CI: 1.2, 4.6, generally; aOR = 3.3, 95% CI: 1.7, 6.42, specifically from family members), experiences of discrimination (aOR = 2.97, 95% CI: 1.43, 6.14), and low life control (aOR = 4.3, 95% CI: 1.86, 10.1) were risk factors for impaired functioning. Qualitative findings suggested how discrimination and lack of control contribute to impaired functioning. Support from the husband's family appeared to be more important to a widow's functioning, compared to from her own parents. Knowledge about risk factors for impaired functioning can help inform interventions for Nepali widows.

Cysteine protected cells from H2O2-induced damage and promoted long-chain fatty acids synthesis in vivo to improve γ-aminobutyric acid production in Levilactobacillus brevis.

Levilactobacillus brevis NPS-QW-145 isolated from kimchi is deficient in glutamate dehydrogenase-encoding gene (gdhA) to form glutamate, hence it required exogenous supplementation of glutamate/monosodium glutamate (MSG) for decarboxylation reaction to produce γ-aminobutyric acid (GABA). However, GABA conversion rate from MSG was relatively low. The individual effect of 20 amino acids on regulating GABA biosynthesis was investigated. Cysteine was selected to significantly improve GABA production from MSG. It was found that Lb. brevis was capable of producing H2O2, cysteine protected Lb. brevis against H2O2-induced oxidative damage to increase cell viability for the enhancement of GABA production. Moreover, cysteine promoted glucose consumption to produce acetyl-CoA for synthesizing long-chain fatty acids to significantly up-regulate GABA biosynthesis. These findings deciphered antioxidative capability of cysteine in Lb. brevis 145 and provided a theoretical basis for fatty acids synthesis-mediated GABA synthesis in Lb. brevis 145, and possibly in other lactic acid bacteria.