Prevalence of adolescent mental disorders in Kenya, Indonesia, and Viet Nam measured by the National Adolescent Mental Health Surveys (NAMHS): a multi-national cross-sectional study.

BACKGROUND: Mental disorders are the leading global cause of health burden among adolescents. However, prevalence data for mental disorders among adolescents in low-income and middle-income countries are scarce with often limited generalisability. This study aimed to generate nationally representative prevalence estimates for mental disorders in adolescents in Kenya, Indonesia, and Viet Nam. METHODS: As part of the National Adolescent Mental Health Surveys (NAMHS), a multinational cross-sectional study, nationally representative household surveys were conducted in Kenya, Indonesia, and Viet Nam between March and December, 2021. Adolescents aged 10-17 years and their primary caregiver were interviewed from households selected randomly according to sampling frames specifically designed to elicit nationally representative results. Six mental disorders (social phobia, generalised anxiety disorder, major depressive disorder, post-traumatic stress disorder, conduct disorder, and attention-deficit hyperactivity disorder) were assessed with the Diagnostic Interview Schedule for Children, Version 5. Suicidal behaviours and self-harm in the past 12 months were also assessed. Prevalence in the past 12 months and past 4 weeks was calculated for each mental disorder and collectively for any mental disorder (ie, of the six mental disorders assessed). Prevalence of suicidal behaviours (ie, ideation, planning, and attempt) and self-harm in the past 12 months was calculated, along with adjusted odds ratios (aORs) to show the association with prevalence of any mental disorder in the past 12 months. Inverse probability weighting was applied to generate national estimates with corresponding 95% CIs. FINDINGS: Final samples consisted of 5155 households (ie, adolescent and primary caregiver pairs) from Kenya, 5664 households from Indonesia, and 5996 households from Viet Nam. In Kenya, 2416 (46·9%) adolescents were male and 2739 (53·1%) were female; in Indonesia, 2803 (49·5%) adolescents were male and 2861 (50·5%) were female; and in Viet Nam, 3151 (52·5%) were male and 2845 (47·4%) were female. Prevalence of any mental disorder in the past 12 months was 12·1% (95% CI 10·9-13·5) in Kenya, 5·5% (4·3-6·9) in Indonesia, and 3·3% (2·7-4·1) in Viet Nam. Prevalence in the past 4 weeks was 9·4% (8·3-10·6) in Kenya, 4·4% (3·4-5·6) in Indonesia, and 2·7% (2·2-3·3) in Viet Nam. The prevalence of suicidal behaviours in the past 12 months was low in all three countries, with suicide ideation ranging from 1·4% in Indonesia (1·0-2·0) and Viet Nam (1·0-1·9) to 4·6% (3·9-5·3) in Kenya, suicide planning ranging from 0·4% in Indonesia (0·3-0·8) and Viet Nam (0·2-0·6) to 2·4% (1·9-2·9) in Kenya, and suicide attempts ranging from 0·2% in Indonesia (0·1-0·4) and Viet Nam (0·1-0·3) to 1·0% (0·7-1·4) in Kenya. The prevalence of self-harm in the past 12 months was also low in all three countries, ranging from 0·9% (0·6-1·3) in Indonesia to 1·2% (0·9-1·7) in Kenya. However, the prevalence of suicidal behaviours and self-harm in the past 12 months was significantly higher among those with any mental disorder in the past 12 months than those without (eg, aORs for suicidal ideation ranged from 7·1 [3·1-15·9] in Indonesia to 14·7 [7·5-28·6] in Viet Nam). INTERPRETATION: NAMHS provides the first national adolescent mental disorders prevalence estimates for Kenya, Indonesia, and Viet Nam. These data can inform mental health and broader health policies in low-income and middle-income countries. FUNDING: The University of Queensland in America (TUQIA) through support from Pivotal Ventures, a Melinda French Gates company.

Vitamin D and depressive symptoms in an early adolescent cohort.

BACKGROUND: To explore the cross-sectional and longitudinal association between vitamin D and depressive symptoms across early adolescence. METHODS: This longitudinal study included 1607 early adolescents [mean (s.d.) age, 12.49 years; 972 (60.5%) males] from the Chinese Early Adolescents Cohort, recruited from a middle school in Anhui Province and followed up annually (2019-2021). Serum 25(OH)D levels were measured in both 2019 and 2021. Self-reports on depression were assessed at each of three time points from 2019 to 2021. RESULTS: In the whole sample, higher baseline serum 25(OH)D levels were linked with a lower risk of cumulative incident depression within two-year follow-ups (adjusted RR = 0.97, 95% CI 0.94-0.99) and the increasing trajectory of depression symptoms across the three waves (adjusted RR = 0.97, 95% CI 0.95-0.99). Baseline vitamin D deficiency (VDD) (adjusted RR = 1.50, 95% CI 1.10-2.05) were associated with an increased risk for the increasing trajectory of depression symptoms across the three waves. Remitted VDD was positively related to one dichotomous depression symptoms across three waves (adjusted OR 2.15, 95% CI 1.15-4.01). The above-mentioned significant association was also found in males. Additionally, baseline VDD (adjusted OR 1.59, 95% CI 1.04-2.44) and persistent VDD (adjusted OR 1.58, 95% CI 1.02-2.60) were linked to an increased risk of having two dichotomous depression symptoms only in males. CONCLUSIONS: Our results highlight a prospective association between baseline vitamin D and depression risk in early adolescents. Additionally, a male-specific association between vitamin D and depression risk was observed. Our findings support a potential beneficial effect of vitamin D supplementation in reducing depression risk in early adolescents.

Adolescent-Parent Relationships and Communication: Consequences for Pregnancy Knowledge and Family Planning Service Awareness.

PURPOSE: We explore three dimensions of parent-adolescent relationships (sexual and reproductive health (SRH) communications, connectedness, and parental monitoring) from the perspective of young adolescents as they relate to pregnancy knowledge and family planning service awareness in four diverse geographic areas ranging from low to high income settings and stratified by sex. METHODS: Analyses utilized baseline data from four Global Early Adolescent Study sites (Shanghai, China; Kinshasa, Democratic Republic of the Congo; Denpasar and Semarang, Indonesia; and New Orleans, United States). Multiple linear regressions were conducted to assess the relationships between key characteristics of parent-adolescent relationships and pregnancy knowledge. Multiple logistic regressions were also conducted to assess relationships between key characteristics of parent-adolescent relationships and family planning service awareness. RESULTS: Across all four sites, communication with a parent about SRH matters was significantly associated with increased pregnancy knowledge among female respondents. Further, girls in Shanghai and New Orleans and boys in Kinshasa who had ever communicated with a parent about SRH matters were significantly more likely to know where to get condoms. Finally, girls who communicated with a parent about any SRH matter were significantly more likely to know where to get other forms of contraception across all four study sites. DISCUSSION: Findings strongly support the importance of SRH communications between young adolescents and their parents. Our findings also suggest that while parental connectedness and monitoring are beneficial they are not replacements for quality parent-adolescent communications about SRH issues that begin early in adolescence before sexual intercourse is initiated.

A chimeric antigen receptor uniquely recognizing MICA/B stress proteins provides an effective approach to target solid tumors.

BACKGROUND: The advent of chimeric antigen receptor (CAR) T cell therapies has transformed the treatment of hematological malignancies; however, broader therapeutic success of CAR T cells has been limited in solid tumors because of their frequently heterogeneous composition. Stress proteins in the MICA and MICB (MICA/B) family are broadly expressed by tumor cells following DNA damage but are rapidly shed to evade immune detection. METHODS: We have developed a novel CAR targeting the conserved α3 domain of MICA/B (3MICA/B CAR) and incorporated it into a multiplexed-engineered induced pluripotent stem cell (iPSC)-derived natural killer (NK) cell (3MICA/B CAR iNK) that expressed a shedding-resistant form of the CD16 Fc receptor to enable tumor recognition through two major targeting receptors. FINDINGS: We demonstrated that 3MICA/B CAR mitigates MICA/B shedding and inhibition via soluble MICA/B while simultaneously exhibiting antigen-specific anti-tumor reactivity across an expansive library of human cancer cell lines. Pre-clinical assessment of 3MICA/B CAR iNK cells demonstrated potent antigen-specific in vivo cytolytic activity against both solid and hematological xenograft models, which was further enhanced in combination with tumor-targeted therapeutic antibodies that activate the CD16 Fc receptor. CONCLUSIONS: Our work demonstrated 3MICA/B CAR iNK cells to be a promising multi-antigen-targeting cancer immunotherapy approach intended for solid tumors. FUNDING: Funded by Fate Therapeutics and NIH (R01CA238039).

Bortezomib induced peripheral neuropathy and single nucleotide polymorphisms in PKNOX1.

We analyzed single nucleotide polymorphisms (SNPs) in PKNOX1 (rs2839629) and in the intergenic region between PKNOX1 and CBS (rs915854) by Sanger sequencing in 88 patients with multiple myeloma treated with bortezomib. All patients (n = 13) harboring a homozygous mutation in PKNOX1 (rs2839629) also had a homozygous mutated rs915854 genotype. Homozygous mutated genotypes of rs2839629 and rs915854 were significantly enriched in patients with painful peripheral neuropathy (PNP) (P < 0.0001), and homozygous mutated rs2839629 genotype was significantly enriched in patients with pain compared to patients with no pain (P = 0.04). In summary, both SNPs rs2839629 and/or rs915854 may be potential biomarkers predicting an increased risk to develop painful PNP under bortezomib.

DRD1 signaling modulates TrkB turnover and BDNF sensitivity in direct pathway striatal medium spiny neurons.

Disturbed motor control is a hallmark of Parkinson's disease (PD). Cortico-striatal synapses play a central role in motor learning and adaption, and brain-derived neurotrophic factor (BDNF) from cortico-striatal afferents modulates their plasticity via TrkB in striatal medium spiny projection neurons (SPNs). We studied the role of dopamine in modulating the sensitivity of direct pathway SPNs (dSPNs) to BDNF in cultures of fluorescence-activated cell sorting (FACS)-enriched D1-expressing SPNs and 6-hydroxydopamine (6-OHDA)-treated rats. DRD1 activation causes enhanced TrkB translocation to the cell surface and increased sensitivity for BDNF. In contrast, dopamine depletion in cultured dSPN neurons, 6-OHDA-treated rats, and postmortem brain of patients with PD reduces BDNF responsiveness and causes formation of intracellular TrkB clusters. These clusters associate with sortilin related VPS10 domain containing receptor 2 (SORCS-2) in multivesicular-like structures, which apparently protects them from lysosomal degradation. Thus, impaired TrkB processing might contribute to disturbed motor function in PD.

Primary Glial Cell and Glioblastoma Morphology in Cocultures Depends on Scaffold Design and Hydrogel Composition.

3D cell cultures better replicate the in vivo environment compared to 2D models. Glioblastoma multiforme, a malignant brain tumor, highly profits from its cellular environment. Here, the U87 glioblastoma cell line in the presence/absence of primary astrocytes is studied. Thiolated hyaluronic acid (HA-SH) hydrogel reinforced with microfiber scaffolds is compared to Matrigel. Hyaluronic acid is a major extracellular matrix (ECM) component in the brain. Poly(ɛ-caprolactone) (PCL) scaffolds are written by meltelectrowriting in a box and triangular shaped design with pore sizes of 200 µm. Scaffolds are composed of 10-layers of PCL microfibers. It is found that scaffold design has an impact on cellular morphology in the absence of hydrogel. Moreover, the used hydrogels have profound influences on cellular morphology resulting in spheroid formation in HA-SH for both the tumor-derived cell line and astrocytes, while cell viability is high. Although cocultures of U87 and astrocytes exhibit cell-cell interactions, polynucleated spheroid formation is still present for U87 cells in HA-SH. Locally restricted ECM production or inability to secrete ECM proteins may underlie the observed cell morphologies. Thus, the 3D reinforced PCL-HA-SH composite with glioma-like cells and astrocytes constitutes a reproducible system to further investigate the impact of hydrogel modifications on cellular behavior and development.

Deep learning-enabled segmentation of ambiguous bioimages with deepflash2.

Bioimages frequently exhibit low signal-to-noise ratios due to experimental conditions, specimen characteristics, and imaging trade-offs. Reliable segmentation of such ambiguous images is difficult and laborious. Here we introduce deepflash2, a deep learning-enabled segmentation tool for bioimage analysis. The tool addresses typical challenges that may arise during the training, evaluation, and application of deep learning models on ambiguous data. The tool's training and evaluation pipeline uses multiple expert annotations and deep model ensembles to achieve accurate results. The application pipeline supports various use-cases for expert annotations and includes a quality assurance mechanism in the form of uncertainty measures. Benchmarked against other tools, deepflash2 offers both high predictive accuracy and efficient computational resource usage. The tool is built upon established deep learning libraries and enables sharing of trained model ensembles with the research community. deepflash2 aims to simplify the integration of deep learning into bioimage analysis projects while improving accuracy and reliability.

Assessing the health, social, educational and economic impact of the COVID-19 pandemic on adolescents in low- and middle-income countries: a rapid review of the literature.

COVID-19 has caused profound health, social, educational and economic devastation around the world, especially among the lives of adolescents in low- and middle-income countries. This paper looks at a wide array of outcomes impacting adolescents' daily lives including health (mental, physical, sexual and reproductive health, vaccine perceptions and overlap between these topics), social relationships (family and peer), education and socio-economic disparities. Both scientific and grey literature between December 2019 and February 2022 were sought from PubMed, Google Scholar and organisations conducting research among adolescents, and coded. A total of 89 articles were included, 73% of which were peer-reviewed; 37% of the articles were from WHO's Western Pacific region; 62% of the articles were cross-sectional; 75% were quantitative. Three major topics emerged in more than half the articles: mental health (72%), education (61%) and socio-economic ramifications (55%). However, there were regional differences in topics and many of them overlapped. The results indicate that, where there has been research, almost all findings have been linked to worse mental health during the pandemic. Overall, remote education was seen as a negative experience. The ramification of school closures on future aspirations, in particular early school leaving, highlights the importance of prioritising education during future pandemics based on the situation within the country. Gender and other disparities have made marginalised adolescents vulnerable to the economic ramifications of containment measures. Given the risks identified, there is a pressing need to put adolescents at the centre of establishing priorities for their health agenda for post-pandemic recovery.

Inflammasome inhibition protects dopaminergic neurons from α-synuclein pathology in a model of progressive Parkinson's disease.

Neuroinflammation has been suggested as a pathogenetic mechanism contributing to Parkinson's disease (PD). However, anti-inflammatory treatment strategies have not yet been established as a therapeutic option for PD patients. We have used a human α-synuclein mouse model of progressive PD to examine the anti-inflammatory and neuroprotective effects of inflammasome inhibition on dopaminergic (DA) neurons in the substantia nigra (SN). As the NLRP3 (NOD-, LRR- and pyrin domain-containing 3)-inflammasome is a core interface for both adaptive and innate inflammation and is also highly druggable, we investigated the implications of its inhibition. Repeat administration of MCC950, an inhibitor of NLRP3, in a PD model with ongoing pathology reduced CD4+ and CD8+ T cell infiltration into the SN. Furthermore, the anti-inflammasome treatment mitigated microglial activation and modified the aggregation of α-synuclein protein in DA neurons. MCC950-treated mice showed significantly less neurodegeneration of DA neurons and a reduction in PD-related motor behavior. In summary, early inflammasome inhibition can reduce neuroinflammation and prevent DA cell death in an α-synuclein mouse model for progressive PD.

A capability framework to inform the fundamental requirements for clinical trial unit development, growth and long term success in outer metropolitan and rural areas.

Background: Participation in clinical trials is linked to improved patient outcomes. Despite this, most trial participants either reside in, or are treated in metropolitan areas. TrialHub developed hub-and-spoke models to support and grow clinical trial units in outer metropolitan and regional/rural centres in order to boost clinical trial engagement and reduce demands of trial participation on patients from outer metropolitan and regional/rural areas. The aim of this project was to establish a capability framework for clinical trial unit growth and development. Methods: An integrative methods study design was used to inform the co-design and development of the capability framework based on data collected in Victoria during 2020-21. This included reviews of the literature and of existing local resources, infrastructure, and staffing; as well as education, mentoring and support, and a needs assessment through multidisciplinary working groups. Results: We developed a capability framework based on the level of support required for outer metropolitan and regional/rural centres with diverse existing capabilities across Victoria. The framework applies a maturity model to assess resources, processes and practices which impact the capacity and capability of centres to conduct trials safely and sustainably. Each level of the model uses a consistent set of factors to describe the core elements required for safe clinical trial delivery. This benchmarking allows targeted investment to ensure safe and high-quality delivery of trials at newly establishing trial units. Conclusion: The capability framework developed by TrialHub provides a basis for staged, planned and successful trial unit development and trial implementation. Further validation of the framework is required.

Measuring the Prevalence of Mental Disorders in Adolescents in Kenya, Indonesia, and Vietnam: Study Protocol for the National Adolescent Mental Health Surveys.

PURPOSE: In low- and middle-income countries, there are limited data on mental disorders among adolescents. To address this gap, the National Adolescent Mental Health Surveys (NAMHS) will provide nationally representative prevalence data of mental disorders among adolescents in Kenya, Indonesia, and Vietnam. This paper details the NAMHS study protocol. METHODS: In each country, a multistage stratified cluster sampling design will be used. Participants will be eligible pairs of adolescents aged 10-17 years and their primary caregiver. Adolescents will be assessed for social phobia, generalized anxiety disorder, major depressive disorder, attention-deficit/hyperactivity disorder, conduct disorder, and post-traumatic stress disorder using the Diagnostic Interview Schedule for Children, version 5. Demographics, risk and protective factors, and service use information will also be collected. In the parallel clinical calibration study, diagnoses of major depressive disorder, social phobia, and generalized anxiety disorder made using the Diagnostic Interview Schedule for Children, version 5 will be calibrated against a diagnostic assessment by in-country clinicians in a separate sample. RESULTS: Data collection for the national survey and clinical calibration study will commence in 2021, with dissemination of findings and methodology due to occur in 2022. CONCLUSIONS: Accurately quantifying the prevalence of mental disorders in adolescents is essential for service planning. NAMHS will address this lack of prevalence data, both within the NAMHS countries and within their respective regions, while establishing a gold-standard methodology for data collection on adolescent mental health in low- and middle-income countries. More broadly, NAMHS will encourage capacity building within each country by establishing linkages between researcher, clinician, government, and other networks.

"If it's really excessive, it can enter your heart": A Mixed Methods Investigation of Bullying Among Early Adolescents in Semarang, Indonesia.

Bullying is a major public health concern for Indonesian adolescents, with well-documented links to a range of emotional and behavioral problems. Despite such evidence, few investigations have employed qualitative methods to illuminate youth's own perceptions of bullying and its psychosocial correlates in this context. The current study aimed to address this gap through an exploration of Indonesian adolescents' motivations, perceptions, and beliefs regarding bullying. Building on prior quantitative findings, an explanatory sequential mixed methods approach was used to better understand the myriad ways in which bullying ties into other psychosocial challenges. Qualitative interviews were conducted with a total of 45 adolescents ages 13 to 14 (25 girls and 20 boys) in two junior high schools in Semarang between October and December 2019. Interviews were audio-recorded, transcribed verbatim, and translated into English for analysis. Qualitative data were then coded using an inductive thematic analysis approach. Interviews yielded contextual insights into adolescents' definitions of bullying including the distinction between "normal" and "serious" bullying; related risk behaviors; key drivers; social and emotional consequences; and coping strategies. Across these thematic categories, a number of noteworthy gender differences emerged, highlighting the role that underlying gender norms can play in driving bullying involvement. Further, findings emphasize the need to develop a locally valid definition of bullying which takes into account the ways in which emotional distress may be both a criterion and a consequence of bullying. Findings can be used to inform bullying prevention programs targeting Indonesian youth.

A latent class approach to understanding patterns of emotional and behavioral problems among early adolescents across four low- and middle-income countries.

Early adolescents (ages 10-14) living in low- and middle-income countries have heightened vulnerability to psychosocial risks, but available evidence from these settings is limited. This study used data from the Global Early Adolescent Study to characterize prototypical patterns of emotional and behavioral problems among 10,437 early adolescents (51% female) living in the Democratic Republic of Congo (DRC), Malawi, Indonesia, and China, and explore the extent to which these patterns varied by country and sex. LCA was used to identify and classify patterns of emotional and behavioral problems separately by country. Within each country, measurement invariance by sex was evaluated. LCA supported a four-class solution in DRC, Malawi, and Indonesia, and a three-class solution in China. Across countries, early adolescents fell into the following subgroups: Well-Adjusted (40-62%), Emotional Problems (14-29%), Behavioral Problems (15-22%; not present in China), and Maladjusted (4-15%). Despite the consistency of these patterns, there were notable contextual differences. Further, tests of measurement invariance indicated that the prevalence and nature of these classes differed by sex. Findings can be used to support the tailoring of interventions targeting psychosocial adjustment, and suggest that such programs may have utility across diverse cross-national settings.

Unbiased analysis of the dorsal root ganglion after peripheral nerve injury: no neuronal loss, no gliosis, but satellite glial cell plasticity.

ABSTRACT: Pain syndromes are often accompanied by complex molecular and cellular changes in dorsal root ganglia (DRG). However, the evaluation of cellular plasticity in the DRG is often performed by heuristic manual analysis of a small number of representative microscopy image fields. In this study, we introduce a deep learning-based strategy for objective and unbiased analysis of neurons and satellite glial cells (SGCs) in the DRG. To validate the approach experimentally, we examined serial sections of the rat DRG after spared nerve injury (SNI) or sham surgery. Sections were stained for neurofilament, glial fibrillary acidic protein (GFAP), and glutamine synthetase (GS) and imaged using high-resolution large-field (tile) microscopy. After training of deep learning models on consensus information of different experts, thousands of image features in DRG sections were analyzed. We used known (GFAP upregulation), controversial (neuronal loss), and novel (SGC phenotype switch) changes to evaluate the method. In our data, the number of DRG neurons was similar 14 d after SNI vs sham. In GFAP-positive subareas, the percentage of neurons in proximity to GFAP-positive cells increased after SNI. In contrast, GS-positive signals, and the percentage of neurons in proximity to GS-positive SGCs decreased after SNI. Changes in GS and GFAP levels could be linked to specific DRG neuron subgroups of different size. Hence, we could not detect gliosis but plasticity changes in the SGC marker expression. Our objective analysis of DRG tissue after peripheral nerve injury shows cellular plasticity responses of SGCs in the whole DRG but neither injury-induced neuronal death nor gliosis.

Telehealth in cancer care during the COVID-19 pandemic.

INTRODUCTION: The Victorian COVID-19 Cancer Network (VCCN) Telehealth Expert Working Group aimed to evaluate the telehealth (TH) experience for cancer patients, carers and clinicians with the rapid uptake of TH in early 2020 during the COVID-19 pandemic. METHODS: We conducted a prospective multi-centre cross-sectional survey involving eight Victorian regional and metropolitan cancer services and three consumer advocacy groups. Patients or their carers and clinicians who had TH consultations between 1 July 2020 and 31 December 2020 were invited to participate in patient and clinician surveys, respectively. These surveys were opened from September to December 2020. RESULTS: The acceptability of TH via both video (82.9%) and phone (70.4%) were high though acceptability appeared to decrease in older phone TH users. Video was associated with higher satisfaction compared to phone (87.1% vs 79.7%) even though phone was more commonly used. Various themes from the qualitative surveys highlighted barriers and enablers to rapid TH implementation. DISCUSSION: The high TH acceptability supports this as a safe and effective strategy for continued care and should persist beyond the pandemic environment, where patient preferences are considered and clinically appropriate. Ongoing support to health services for infrastructure and resources, as well as expansion of reimbursement eligibility criteria for patients and health professionals, including allied health and nursing, are crucial for sustainability.