A Molecular Docking and Pharmacokinetic Prediction of Thiazolidine-2, 4-dione Derivatives: Toward Novel Therapeutic Targets for Type-2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is a leading endocrine disorder that affects millions of people worldwide. It is characterized by hyperglycemia and high insulin resistance. The commonly prescribed oral therapeutic for insulin resistance in T2DM is Thiazolidine-2, 4-diones (TZDs). TZDs are a class of oral hypoglycemic agents that act on Peroxisome proliferator activating receptor-γ (PPAR-γ) receptors and are mainly expressed in the adipose tissues. In this work, we derive novel classes of TZDs and predict the nature of structural affinity using docking studies against the PPAR-γ.

Comparative Efficacy of Oxitard Capsules and Immusante Tablets in Early Stages of Oral Submucous Fibrosis - A Randomized Controlled Trial

Objective: Oral submucous fibrosis (OSMF) is manifested by symptoms such as palpable fibrotic bands, ulceration, presence of stiffness in the mouth and lip, xerostomia, pigmentation in the oral mucosal layer, and burning sensation and drying of the mouth. It poses a challenge for researchers as there is no viable therapy for this gradually debilitating disorder with a high malignancy potential. Ayurveda is a traditional medicinal practice of the past and present times which can be useful in providing a viable cure. Thus, the current study was designed to assess and compare the effect of Oxitard capsule and Immusante tablet on the clinical and subjective symptoms of OSMF. Material and Methods: The study included 36 patients with clinically diagnosed OSMF who were split evenly into two groups: Group A, the Oxitard group, and Group B, the Immusante group. For three months, Group A received two Oxitard capsules twice daily, while Group B received two Immusante tablets twice daily. At regular intervals, the clinical parameters were evaluated, and the data were analysed using repeated measures ANOVA and the Bonferroni post hoc test. P-value≤0.05 was regarded as statistically significant. Results: On assessment of mouth opening, tongue protrusion, cheek flexibility and subjective symptoms there was significant improvement reported in both groups. In group comparison, the Oxitard and Immusante groups showed a significant difference in cheek flexibility at 3 months. There were no significant differences in subjective symptoms in either of the groups pre- and post-treatment. Conclusion: Efficacy of both the drugs were equall was found to be similar when used as an adjunct to tobacco cessation counselling in the management of early stages of oral submucous fibrosis when used as an adjunct to behavioral management

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

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.</p

Bacterial Isolation and Evaluation for Degradation of Unpretreated LDPE from Waste Dump Soils

Plastic pollution is a universal problem, and microbial management of plastic waste represents a promising area of biotechnological research. This study investigated the ability of bacterial strains which were isolated from landfill soil to degrade Low-Density Polyethylene (LDPE). Strains obtained via serial dilution were screened for LDPE degradation on Minimal Essential Medium (MEM) with hexadecane. Nine isolates producing clearance zones on hexadecane-supplemented MEM were further tested for biofilm formation on LDPE sheets. High cell surface hydrophobicity isolates (>10%) were selected for detailed biodegradation studies. The C-8 bacterial isolate showed the highest LDPE weight loss (3.57%) and exhibited maximum laccase (0.0219 U/mL) and lipase activity (19 mm) among all bacterial isolates after 30 days. Weight loss was further validated by FTIR and SEM analysis. FTIR analysis revealed that in comparison to control, changes in peak were observed at 719 cm-1 (C-H bending), 875.67 cm-1 (C-C vibrations), 1307.07 cm-1 (C-O stretching), 1464.21 cm-1 (C-H bending), 2000-1650 cm-1 (C-H bending), 2849.85 cm-1 (C-H stretching) in microbial treated LDPE sheets. The treated LDPE also displayed increase in carbonyl index (upto 2.5 to 3 folds), double bond index (1 to 2-fold) and internal double bond index (2 to 2.5-fold) indicating oxidation and chain scission in the LDPE backbone. SEM analysis showed substantial micrometric surface damage on the LDPE film, with visible cracks and grooves. Using 16S rRNA gene sequencing, the C-8, C-11, C-15 and C-19 isolate were identified as Bacillus paramycoides, Micrococcus luteus, Bacillus siamensis and Lysinibacillus capsica, respectively

Developing knowledge-based psychotherapeutic competencies in non-specialist providers:A pre-post study with a nested randomized 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

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

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

Effectiveness of a brief lay counsellor-delivered, problem-solving intervention for adolescent mental health problems in urban, low-income schools in India: a randomised controlled trial.

BACKGROUND: Mental health problems are a leading cause of disability in adolescents worldwide. Problem solving is a well-tested mental health intervention in many populations. We aimed to investigate the effectiveness of a brief, transdiagnostic problem-solving intervention for common adolescent mental health problems when delivered by non-specialist school counsellors in New Delhi, India. METHODS: This randomised trial was done in six government-run schools (three all-boys schools, two all-girls schools, and one co-educational school) that serve low-income communities. We recruited participants from grades 9 to 12 (ages 12-20 years) by selecting students with persistently elevated mental health symptoms accompanied by distress or functional impairment. Clinical eligibility criteria were assessed by research assistants using the Hindi-language version of the Strengths and Difficulties Questionnaire (SDQ), with reference to locally validated borderline cutoff scores of 19 or greater for boys and 20 or greater for girls on the SDQ Total Difficulties scale, an abnormal score of 2 or more on the SDQ Impact scale, and persistence of more than 1 month on the SDQ Chronicity index. Participants were randomly allocated (1:1) to problem solving delivered through a brief (2-3 week) counsellor-led intervention with supporting printed materials (intervention group), or problem solving delivered via printed booklets alone (control group). Primary outcomes were adolescent-reported mental health symptoms (SDQ Total Difficulties scale) and idiographic psychosocial problems (Youth Top Problems [YTP]) at 6 weeks. Primary analyses were done on an intention-to-treat basis at the 6-week endpoint. The trial is registered with ClinicalTrials.gov, NCT03630471. FINDINGS: Participants were enrolled between Aug 20, and Dec 4, 2018. 283 eligible adolescents were referred to the trial, and 251 (89%) of these were enrolled (mean age 15·61 years; 174 [69%] boys). 125 participants were allocated to each group (after accounting for one participant in the intervention group who withdrew consent after randomisation). Primary outcome data were available for 245 (98%) participants. At 6 weeks, the mean YTP scores were 3·52 (SD 2·66) in the intervention group and 4·60 (2·75) in the control group (adjusted mean difference -1·01, 95% CI -1·63 to -0·38; adjusted effect size 0·36, 95% CI 0·11 to 0·61; p=0·0015). The mean SDQ Total Difficulties scores were 17·48 (5·45) in the intervention group and 18·33 (5·45) in the control group (-0·86, -2·14 to 0·41; 0·16, -0·09 to 0·41; p=0·18). We observed no adverse events. INTERPRETATION: A brief lay counsellor-delivered problem-solving intervention combined with printed booklets seemed to have a modest effect on psychosocial outcomes among adolescents with diverse mental health problems compared with problem-solving booklets alone. This counsellor-delivered intervention might be a suitable first-line intervention in a stepped care approach, which is being evaluated in ongoing studies. FUNDING: Wellcome Trust