Adolescent engagement in a stepped care, transdiagnostic mental health intervention delivered in Indian schools.

Given the relationship between poor engagement and worse treatment outcomes, improving engagement has been the focus of attention in recent years. Engagement is a particular challenge among minoritized and otherwise challenged youth, such as those from socioeconomically disadvantaged groups, including youth in low- and middle-income countries (LMICs), where they face lower levels of access to resources, including mental health treatment. The present study describes engagement challenges that arose in an uncontrolled pre-post evaluation of a school-based, modular, multi-problem, stepped-care intervention delivered in urban Indian communities. Specifically, the study aimed to (1) characterize barriers and facilitators of youth treatment engagement; and (2) evaluate treatment acceptability and fit of treatment from the youth perspective. Youth participants completed semi-structured interviews, which were transcribed and coded using thematic analysis. Participants described numerous facilitators to engagement (e.g., positive therapeutic relationship) and reported high overall satisfaction with the intervention, while also identifying barriers to engagement (e.g., concerns about confidentiality) and offering suggestions to increase fit and acceptability (e.g., more visually appealing treatment materials). Findings highlight ways in which engagement can be enhanced and implementation supports improved to maximize treatment effectiveness among minoritized and disadvantaged youth in LMICs. Supplementary Information: The online version contains supplementary material available at 10.1007/s44202-024-00154-1.

Study on Biofilm Formation Among Enterococcus Isolates and Association With Their Antibiotic Resistance Patterns.

Background Enterococci are a part of the normal intestinal flora of humans. They have emerged as one of the leading causes of nosocomial infection. The evolved antibiotic resistance mechanisms coupled with the virulence properties of enterococci have made it a successful pathogen. Aim This study aimed to determine the ability of biofilm formation among the clinical enterococci isolates and the antimicrobial resistance pattern of the strains. Materials and methods Clinical samples of patients who attended Saveetha Medical College and Hospital, Chennai, India, over six months. Identification and characterization of Enterococcus species were done using various biochemical tests. Antibiotic susceptibility patterns for each isolate were performed using the Kirby- Bauer disc diffusion method. Results The formation of biofilm formation was detected using the microtiter plate method. In total, 90 Enterococcus species were isolated; Enterococcus faecalis were 63 (70%), Enterococcus faecium were 25 (28%) and Enterococcus gallinarum were 2 (2%)independently. E. faecalis displayed advanced resistance rates compared to other Enterococcus species. Resistance against penicillin was found in 42 strains (47%) and resistance to ampicillin was observed in 39 strains (43%). This was followed by resistance to high-level gentamicin in 35 strains (39%) and resistance to ciprofloxacin in 32 strains (36%). Resistance to vancomycin and linezolid also were noted in some strains. Conclusion Our results indicate that E. faecalis exhibits an increasing rate of antimicrobial resistance but lower biofilm conformation. The unique traits of E. faecalis raise concerns for the associated infections, especially hospital-acquired infections.

Coach-Supported Versus Self-guided Digital Training Course for a Problem-solving Psychological Intervention for Nonspecialists: Protocol for a Pre-Post Nested Randomized Controlled Trial.

BACKGROUND: Psychosocial interventions delivered by nonspecialists can be effective at reducing common adolescent mental health problems in low-resource settings. However, there is a lack of evidence on resource-efficient methods for building capacity to deliver these interventions. OBJECTIVE: The objective of this study is to evaluate the effects of a digital training (DT) course, delivered in a self-guided format or with coaching, on nonspecialists' competency to deliver a problem-solving intervention intended for adolescents with common mental health problems in India. METHODS: We will conduct a pre-post study with a nested parallel, 2-arm, individually randomized controlled trial. The study aims to recruit 262 participants, randomized 1:1 to receive either a self-guided DT course or a DT course with weekly individualized coaching provided remotely by telephone. In both arms, the DT will be accessed over 4 to 6 weeks. Participants will be nonspecialists (ie, without prior practice-based training in psychological therapies) recruited from among university students and affiliates of nongovernmental organizations in Delhi and Mumbai, India. RESULTS: Outcomes will be assessed at baseline and 6 weeks post randomization using a knowledge-based competency measure that incorporates a multiple-choice quiz format. The primary hypothesis is that self-guided DT will lead to increased competency scores among novices with no prior experience of delivering psychotherapies. The secondary hypothesis is that digital training with coaching will have an incremental effect on competency scores compared with DT alone. The first participant was enrolled on April 4, 2022. CONCLUSIONS: The study will address an evidence gap on the effectiveness of training methods for nonspecialist providers of adolescent mental health interventions in low-resource settings. The findings from this study will be used to support wider efforts to scale up evidence-based mental health interventions for young people. TRIAL REGISTRATION: ClinicalTrials.gov NCT05290142; https://clinicaltrials.gov/ct2/show/NCT05290142. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/41981.

Feasibility and Acceptability of a Remote Stepped Care Mental Health Programme for Adolescents during the COVID-19 Pandemic in India.

Remote mental health services were rapidly deployed during the COVID-19 pandemic, yet there is relatively little contemporaneous evidence on their feasibility and acceptability. This study assessed the feasibility and acceptability of a stepped care mental health programme delivered remotely by lay counsellors to adolescents in New Delhi, India, during a period of 'lockdown'. The programme consisted of a brief problem-solving intervention ("Step 1") followed by a tailored behavioural module ("Step 2") for non-responders. We enrolled 34 participants (M age = 16.4 years) with a self-identified need for psychological support. Feasibility and acceptability were assessed through quantitative process indicators and qualitative interviews (n = 17 adolescents; n = 5 counsellors). Thirty-one (91%) adolescents started Step 1 and 16 (52%) completed the planned Step 1 protocol. Twelve (75%) of the Step 1 completers were non-responsive. Eight (67%) non-responsive cases started Step 2, all of whom met response criteria when reassessed at 12 weeks post-enrolment. Adolescents favoured voice-only sessions over video-calls due to privacy concerns and difficulties accessing suitable devices. Counsellors noted challenges of completing remote sessions within the allotted time while recognising the importance of supervision for developing competence in new ways of working. Both adolescents and counsellors discussed the importance of working collaboratively and flexibly to fit around individual preferences and circumstances. Disentangling pandemic-specific barriers from more routine challenges to remote delivery should be a focus of future research.

Developing knowledge-based psychotherapeutic competencies in non-specialist providers: A pre-post study with a nested randomised controlled trial of a coach-supported versus self-guided digital training course for a problem-solving psychological intervention in India.

We evaluated a digital learning programme for non-specialists to develop knowledge-based competencies in a problem-solving intervention for adolescents to examine the overall impact of training on knowledge-based competencies among learners; and to compare the effects of two training conditions (self-guided digital training with or without coaching) in a nested parallel, two-arm, individually randomised controlled trial. Eligible participants were 18 or older; fluent in Hindi or English; able to access digital training; and had no prior experience of delivering structured psychotherapies. 277 participants were enrolled from 31 March 2022 to 19 June 2022 of which 230 (83%) completed the study. There was a significant increase in competency score from pre-training (Mean = 7.01, SD = 3.29) to post-training (Mean = 8.88, SD = 3.80), 6 weeks after the pre-training assessment. Knowledge competency scores showed larger increase among participants randomised to the coaching arm (AMD = 1.09, 95% CI 0.26-1.92, p = 0.01) with an effect size (d) of 0.33 (95% CI 0.08-0.58). More participants completed training in the coaching arm (n = 96, 69.6%) compared to the self-guided training arm (n = 56, 40.3%). In conclusion, a coach-supported remote digital training intervention is associated with enhanced participation by learners and increased psychotherapeutic knowledge competencies.

A qualitative analysis of collaborative efforts to build a school-based intervention for multiple common adolescent mental health difficulties in India.

Introduction: In low- and middle-income countries (LMICs), the gap between need for mental health (MH) treatment and access to services is stark, particularly among children and adolescents. In service of addressing this treatment gap, the current study provides an in-depth illustration of later-stage collaborative design of a school-based, transdiagnostic MH intervention in New Delhi and Goa, India, using a combination of contextual insights from local stakeholders and knowledge derived from the global evidence base. Methods: Using an inductive-deductive approach to qualitative thematic analysis, we examined coded data from qualitative sources related to experiences of developing and implementing an intervention prototype. These sources included notes from meetings attended by treatment development team members and providers, written feedback on protocol materials (e.g., provider manual, student handouts), field notes reflecting researcher observations, and minutes from weekly clinical supervision meetings. Results: Results revealed that codes involving cultural/contextual considerations, protocol material and content, and intervention complexity arose consistently throughout treatment development and across document types, illustrating their central role in finalizing protocol design. Discussion: These findings have implications for the future of mental health treatment development and implementation globally.

P300 promotes tumor recurrence by regulating radiation-induced conversion of glioma stem cells to vascular-like cells.

Glioma stem cells (GSC) exhibit plasticity in response to environmental and therapeutic stress leading to tumor recurrence, but the underlying mechanisms remain largely unknown. Here, we employ single-cell and whole transcriptomic analyses to uncover that radiation induces a dynamic shift in functional states of glioma cells allowing for acquisition of vascular endothelial-like and pericyte-like cell phenotypes. These vascular-like cells provide trophic support to promote proliferation of tumor cells, and their selective depletion results in reduced tumor growth post-treatment in vivo. Mechanistically, the acquisition of vascular-like phenotype is driven by increased chromatin accessibility and H3K27 acetylation in specific vascular genes allowing for their increased expression post-treatment. Blocking P300 histone acetyltransferase activity reverses the epigenetic changes induced by radiation and inhibits the adaptive conversion of GSC into vascular-like cells and tumor growth. Our findings highlight a role for P300 in radiation-induced stress response, suggesting a therapeutic approach to prevent glioma recurrence.

Diabetic Embryopathies.

Diabetic embryopathy is defined as congenital anomalies that are linked to maternal diabetes. The association between diabetes and fetal, neonatal, and long-term complications is well-established. These complications include organ or structural maldevelopment, fetal growth abnormalities, and learning/psychiatric comorbidities. Recent studies have elucidated the pathophysiology behind these conditions and outlined new management approaches. Caudal regression syndrome, also known as sacral agenesis, is a well-known but less described complication of maternal diabetes. The purpose of this review is to summarize existing research on common neonatal morbidities in infants of mothers with diabetes with a focus on caudal regression syndrome and its long-term associations.

Serine biosynthesis as a novel therapeutic target for dilated cardiomyopathy.

AIMS: Genetic dilated cardiomyopathy (DCM) is a leading cause of heart failure. Despite significant progress in understanding the genetic aetiologies of DCM, the molecular mechanisms underlying the pathogenesis of familial DCM remain unknown, translating to a lack of disease-specific therapies. The discovery of novel targets for the treatment of DCM was sought using phenotypic sceening assays in induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) that recapitulate the disease phenotypes in vitro. METHODS AND RESULTS: Using patient-specific iPSCs carrying a pathogenic TNNT2 gene mutation (p.R183W) and CRISPR-based genome editing, a faithful DCM model in vitro was developed. An unbiased phenotypic screening in TNNT2 mutant iPSC-derived cardiomyocytes (iPSC-CMs) with small molecule kinase inhibitors (SMKIs) was performed to identify novel therapeutic targets. Two SMKIs, Gö 6976 and SB 203580, were discovered whose combinatorial treatment rescued contractile dysfunction in DCM iPSC-CMs carrying gene mutations of various ontologies (TNNT2, TTN, LMNA, PLN, TPM1, LAMA2). The combinatorial SMKI treatment upregulated the expression of genes that encode serine, glycine, and one-carbon metabolism enzymes and significantly increased the intracellular levels of glucose-derived serine and glycine in DCM iPSC-CMs. Furthermore, the treatment rescued the mitochondrial respiration defects and increased the levels of the tricarboxylic acid cycle metabolites and ATP in DCM iPSC-CMs. Finally, the rescue of the DCM phenotypes was mediated by the activating transcription factor 4 (ATF4) and its downstream effector genes, phosphoglycerate dehydrogenase (PHGDH), which encodes a critical enzyme of the serine biosynthesis pathway, and Tribbles 3 (TRIB3), a pseudokinase with pleiotropic cellular functions. CONCLUSIONS: A phenotypic screening platform using DCM iPSC-CMs was established for therapeutic target discovery. A combination of SMKIs ameliorated contractile and metabolic dysfunction in DCM iPSC-CMs mediated via the ATF4-dependent serine biosynthesis pathway. Together, these findings suggest that modulation of serine biosynthesis signalling may represent a novel genotype-agnostic therapeutic strategy for genetic DCM.

"You're a 'high-risk' customer": A qualitative study of women's experiences of receiving information from health professionals regarding health problems or complications in pregnancy.

BACKGROUND: Experiencing complications in pregnancy is stressful for women and can impact on fetal and maternal outcomes. Supportive encounters with health professionals can reduce the worry women experience. Further research is needed to understand women's perspectives on communicating with their healthcare providers about their concerns. AIM: This study explored women's experiences of receiving information about pregnancy complications from healthcare providers and their interactions with multiple professionals and services during pregnancy. METHODS: This was a qualitative interpretive study. Semi-structured interviews were conducted with 20 women experiencing pregnancy complications recruited from antenatal services at two hospitals in Sydney. Inductive thematic analysis was used to analyse the data. FINDINGS: Women had a range of reactions to their diagnoses, including concern for their baby, for themselves and for their labour. Most women reported that communication with healthcare providers was distressing, they were not listened to and staff used insensitive, abrupt language. Women were also distressed by delays in education, receiving contradictory information and having to repeatedly share their stories with different health professionals. In some cases, this damaged the therapeutic relationship and reduced trust towards healthcare providers. Midwives were generally preferred over doctors because they had a more woman-centred approach. CONCLUSION: To improve women's experiences of care for pregnancy complications, it is critical to improve the communication skills of maternity service providers. Women's need for information, resources and support can best be provided by continuity of care with a named health professional, for example, a midwife working within an integrated multidisciplinary antenatal service model.

Health benefits of cyanidin-3-glucoside as a potent modulator of Nrf2-mediated oxidative stress.

Berries are natural sources of anthocyanins, especially cyanidin-3-glucoside (C3G), and exhibit significant antioxidant, antidiabetic, anti-inflammatory, and cytoprotective effects against various oxidative stress-induced disorders. C3G and its metabolites possess higher absorption and bioavailability, and interaction with gut microbiota may enhance their health benefits. Various in vitro studies have shown the reactive oxygen species (ROS)-mitigating potential of C3G. However, in in vivo models, C3G exerts its cytoprotective properties by regulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant-responsive element (ARE) pathway. Despite existing reports stating various health benefits of C3G, its antioxidant potential by modulating the Nrf2 pathway remains less identified. This review discusses the Nrf2-mediated antioxidant response of C3G in modulating oxidative stress against DNA damage, apoptosis, carcinogen toxicity, and inflammatory conditions. Furthermore, we have reviewed the recent clinical trial data to establish cross talk between a berry-rich diet and disease prevention.

ECHO Autism: Evaluation of Participants' Perceptions of Collaborative Telementoring Network.

Introduction: Primary care clinicians report inadequate training and lack of support regarding identification of early signs of Autism Spectrum Disorder (ASD), resulting in later diagnosis and poor outcomes. The objective of this study was to evaluate the perception of participants in ECHO Autism project regarding the value of the virtual collaborative as a mentoring tool. Methods: We completed a retrospective cross-sectional study of post-virtual clinic surveys of all participants who attended Autism ECHO from September 2, 2015 to June 5, 2019. Results: There were 87 Autism ECHO sessions held, with 83 didactic presentations. A total of 92 de-identified patient cases were discussed with 490 unique learners in attendance. Participants reported increase in self-efficacy in identifying ASD symptoms in children, assessing medical comorbidities, and learning new information. Discussion: Continuing education platforms in healthcare professions are increasingly embracing virtual live-interactive conferences. They provide opportunities to connect with experts, but also hear from peers regarding real-life case examples. During COVID-19 pandemic ECHO Autism was a lifeline for rural providers and will likely continue to increase in participation.

The long-term consequence of salivary contamination at various stages of adhesive application and clinically feasible remedies to decontaminate.

OBJECTIVE: To analyse the bond quality in dentine post-ageing after salivary contamination and decontamination at different stages of dental adhesive application. MATERIALS AND METHODS: A total of 1120 human dentine specimens were randomly allocated to 14 groups for four intervals (n = 20) to be treated with a self-etching (SE) and universal (U) adhesive. The saliva contamination and decontamination were implemented after surface preparation, after primer application (for SE) and after adhesive curing. The decontamination groups were either rinsed and air-dried or rinsed, air-dried and reapplied with adhesive. They were stored (37 °C, distilled water) for four intervals (1 week, 1 month, 3 months and 1 year) and subjected to shear bond strength (SBS) test at a crosshead speed of 0.5 mm/min. RESULT: One-way ANOVA with Tukey's test (α = 0.05) revealed significant reduction in SBS in all the groups in U adhesive compared with the control group at 1 week (p < 0.0001) and in SE when the contamination took place after primer application. However, decontamination improved the SBS in SE but not in U adhesive. The univariate analysis confirmed significant influences (p < 0.0001) seen by treatment procedure ([Formula: see text]=0.075), type of adhesive ([Formula: see text] = 0.328), ageing ([Formula: see text] = 0.13), experimental groups ([Formula: see text] = 0.518), and the stage of influence ([Formula: see text] = 0.60). CONCLUSION: Saliva contamination is detrimental after primer application in SE but, decontamination regained the SBS and maintained it over time. In U adhesive, SBS deteriorated over time irrespective of the contamination. CLINICAL RELEVANCE: Salivary contamination showed different influences on SBS at various stages of restoration with contemporary dental adhesives.

Truth and Transparency in Crisis Pregnancy Centers.

The prevalence of crisis pregnancy centers (CPCs), their false claims, and the real harm they cause necessitate public education about their unethical practices. Also called "pregnancy resource centers" and "pregnancy support centers," CPCs are nonmedical institutions designed to deceive women seeking comprehensive pregnancy care, as their volunteers are instructed to pedal misinformation about reproductive health care.

Concise Review: Precision Matchmaking: Induced Pluripotent Stem Cells Meet Cardio-Oncology.

As common chemotherapeutic agents are associated with an increased risk of acute and chronic cardiovascular complications, a new clinical discipline, cardio-oncology, has recently emerged. At the same time, the development of preclinical human stem cell-derived cardiovascular models holds promise as a more faithful platform to predict the cardiovascular toxicity of common cancer therapies and advance our understanding of the underlying mechanisms contributing to the cardiotoxicity. In this article, we review the recent advances in preclinical cancer-related cardiotoxicity testing, focusing on new technologies, such as human induced pluripotent stem cell-derived cardiomyocytes and tissue engineering. We further discuss some of the limitations of these technologies and present future directions. Stem Cells Translational Medicine 2019;8:758&767.

A rare presentation of lobular panniculitis in the oral cavity of a 2-year-old patient.

Pannicultis is a rare disorder which usually affects the organ and tissue which are abundant in fat cells. It causes fatty degeneration of the fat cells and the diagnosis is usually made histologically. Here we present you a rare case of lobular pannicultis which occurred in a 2 year old patient in its oral cavity.

Dynamic DNA Methylation in Plant Growth and Development.

DNA methylation is an epigenetic modification required for transposable element (TE) silencing, genome stability, and genomic imprinting. Although DNA methylation has been intensively studied, the dynamic nature of methylation among different species has just begun to be understood. Here we summarize the recent progress in research on the wide variation of DNA methylation in different plants, organs, tissues, and cells; dynamic changes of methylation are also reported during plant growth and development as well as changes in response to environmental stresses. Overall DNA methylation is quite diverse among species, and it occurs in CG, CHG, and CHH (H = A, C, or T) contexts of genes and TEs in angiosperms. Moderately expressed genes are most likely methylated in gene bodies. Methylation levels decrease significantly just upstream of the transcription start site and around transcription termination sites; its levels in the promoter are inversely correlated with the expression of some genes in plants. Methylation can be altered by different environmental stimuli such as pathogens and abiotic stresses. It is likely that methylation existed in the common eukaryotic ancestor before fungi, plants and animals diverged during evolution. In summary, DNA methylation patterns in angiosperms are complex, dynamic, and an integral part of genome diversity after millions of years of evolution.

Adverse effects of salivary contamination for adhesives in restorative dentistry. A literature review.

PURPOSE: To review and critically analyze the literature concerning the influence of salivary contamination on the bond quality of adhesives used in restorative materials by comparing and contrasting the different adhesive materials. METHODS: A detailed search on PUBMED, Cochrane Library, Google Scholar and Web of Science was carried out to identify publications on salivary contamination and dental adhesive materials, from 1990-2017 (March) which resulted in a total of 6,202 web-identified publications. After screening titles/abstracts and de-duplicating, 54 publications were selected that matched the requirements for this review. The condition for selection was English literature concerning the effect of salivary contamination on the adhesives used in restorative dentistry. The obtained articles were systematically evaluated. RESULTS: Salivary contamination of adhesives during restorative procedures statistically (64.6%) showed an adverse effect on adhesives, occurring either at one or many stages of restoration. Methodological dissimilarities impeded the direct comparison of the selected studies. Nevertheless, the 2-step etch and rinse adhesives were relatively less vulnerable to salivary contamination than the others. 65% of the evaluated studies for decontamination achieved improved bonding when the contaminated surface was subjected to some kind of decontamination procedure. However, the duration and other specificities were not standard in all the evaluations and need further research to assess the course of action. It is necessary to do long term studies to evaluate the effectiveness of contaminated adhesive over time. CLINICAL SIGNIFICANCE: Salivary contamination is a potential cause for poor bond quality of adhesive systems during restorative procedures and to provide a successful treatment, proper care must be taken to ensure the operating area is free from contamination. Understanding the properties of the materials and its constituents as well as considering measures to manage the potential vulnerabilities due to salivary contamination in the area of bonding might help a clinician to produce better results.

Alternative Splicing of Titin Restores Diastolic Function in an HFpEF-Like Genetic Murine Model (TtnΔIAjxn).

RATIONALE: Patients with heart failure with preserved ejection fraction (HFpEF) experience elevated filling pressures and reduced ventricular compliance. The splicing factor RNA-binding motif 20 (RBM20) regulates the contour length of titin's spring region and thereby determines the passive stiffness of cardiomyocytes. Inhibition of RBM20 leads to super compliant titin isoforms (N2BAsc) that reduce passive stiffness. OBJECTIVE: To determine the therapeutic potential of upregulating compliant titin isoforms in an HFpEF-like state in the mouse. METHODS AND RESULTS: Constitutive and inducible cardiomyocyte-specific RBM20-inhibited mice were produced on a Ttn(ΔIAjxn) background to assess the effect of upregulating compliant titin at the cellular and organ levels. Genetic deletion of the I-band-A-band junction (IAjxn) in titin increases strain on the spring region and causes a HFpEF-like syndrome in the mouse without pharmacological or surgical intervention. The increased strain represents a mechanical analog of deranged post-translational modification of titin that results in increased passive myocardial stiffness in patients with HFpEF. On inhibition of RBM20 in Ttn(ΔIAjxn) mice, compliant titin isoforms were expressed, diastolic function was normalized, exercise performance was improved, and pathological hypertrophy was attenuated. CONCLUSIONS: We report for the first time a benefit from upregulating compliant titin isoforms in a murine model with HFpEF-like symptoms. Constitutive and inducible RBM20 inhibition improves diastolic function resulting in greater tolerance to exercise. No effective therapies exists for treating this pervasive syndrome; therefore, our data on RBM20 inhibition are clinically significant.