Unraveling the regulatory landscape of Parkinson disease: A molecular symphony of miRNAs, transcription factors, and high-risk genes.

MicroRNAs (miRNAs) have emerged as critical regulators of post-transcriptional gene expression, impacting various biological processes (development, differentiation, and progression). In medicine, miRNAs are promising diagnostic biomarkers for neurodegenerative diseases, including Parkinson's disease (PD). The current study aims at exploring the role of miRNAs and transcription factors (TFs) in regulating genes-associated with PD. Deploying bioinformatics tools, the study identifies specific miRNAs and TFs involved in PD and their potential connections to the organ-disease junction. Notably, certain miRNAs are found to be highly expressed in brain, than compared to blood. Furthermore, the study explores the expression patterns of PD-related genes in different regions of the brain and attempts to construct complex network of interactions contributing to PD pathogenesis. Additionally, the regulatory relationship of two miRNAs namely hsa-miR-375-3p and hsa-miR-423-3p with TFs are well examined. Overall, the study provides a comprehensive moon-shot view of the molecular aspects of PD and their potential therapeutic targets which could be further used as diagnostic biomarkers in early detection, drug design and development attributing towards precision medicine.

STEPS - a patient centric and low-cost solution to ensure standards of TB care to patients reaching private sector in India.

BACKGROUND: More than half of the TB patients in India seek care from the private sector. Two decades of attempts by the National TB Program to improve collaboration between the public and private sectors have not worked except in a few innovative pilots. The System for TB Elimination in Private Sector (STEPS) evolved in 2019 as a solution to ensure standards of TB care to every patient reaching the private sector. We formally evaluated the STEPS to judge the success of the model in achieving its outcomes and to inform decisions about scaling up of the model to other parts of the country. METHODS: An evaluation team was constituted involving all relevant stakeholders. A logic framework for the STEPS model was developed. The evaluation focused on (i) processes - whether the activities are taking place as intended and (ii) proximal outcomes - improvements in quality of care and strengthening of TB surveillance system. We (i) visited 30 randomly selected STEPS centres for assessing infrastructure and process using a checklist, (ii) validated the patient data with management information system of National TB Elimination Program (NTEP) by telephonic interview of 57 TB patients (iii) analysed the quality of patient care indicators over 3 years from the management information system (iv) conducted in-depth interviews (IDI) with 33 beneficiaries and stakeholders to understand their satisfaction and perceived benefits of STEPS and (v) performed cost analysis for the intervention from the perspective of NTEP, private hospital and patients. RESULTS: Evaluation revealed that STEPS is an acceptable model to all stakeholders. IDIs revealed that all patients were satisfied about the services received. Data in management information system of NTEP were consistent with the hospital records and with the information provided by the patient. Quality of TB care indicators for patients diagnosed in private hospitals showed improvements over years as proportion of TB patients notified from private sector with a microbiological confirmation of diagnosis improved from 25% in 2018 to 38% in 2020 and the documented treatment success rate increased from 33% (2018 cohort) to 88% (2019 cohort). Total additional programmatic cost (deducting cost for patient entitlements) per additional patient with successful treatment outcome was estimated to be 67 USD. Total additional expense/business loss for implementing STEPS for the hospital diagnosing 100 TB patients in a year was estimated to be 573 USD while additional minimum returns for the hospital was estimated to be 1145 USD. CONCLUSION: Evaluation confirmed that STEPS is a low cost and patient-centric strategy. STEPS successfully addressed the gaps in the quality of care for patients seeking care in the private sector and ensured that services are aligned with the standards of TB care. STEPS could be scaled up to similar settings.

Diet with Low Molecular Weight Chitosan exerts neuromodulation in Rotenone induced Drosophila model of Parkinson's disease.

Rotenone (ROT) is well known pesticide been used in agriculture due to its low cost and rapid action. This has also been widely used to establish Parkinson's disease (PD) models in rodents. Here we have evaluated the role of well established potent molecule 'Low Molecular Weight Chitosan (LMWC)' against ROT induced neurotoxicity in Drosophila melanogaster. Male adult flies (8-10 days) were induced for neurotoxicity using ROT (500 µM) and treated with LMWC (5 & 10 mg/mL basal media) during 7 days experiment. Subsequently, neurodegenerative and behavioural parameters were assessed. As a result, flies exposed to ROT alone showed decreased locomotor behaviour in negative geotaxis and open-field studies and had a higher incidence of mortality compared to control group. These effects were accompanied by decrease in dopamine level, ETC complexes and increase in reactive oxygen species (ROS) production and cholinergic activities in head and body of the flies, suggesting ROT was able to induce oxidative stress. Co-exposure of LMWC reversed the ROT induced locomotor impairment, exploratory deficits and changes the biochemical parameters to normal level and increased the survival rate to 16 days. Thus, we suggested LMWC may be considered as better supplement in the prevention and management of Parkinson's disease.