Effect of Bacille-Calmette-Guerin vaccine against rotenone-induced Parkinson's disease: Role of neuroinflammation and neurotransmitters.

BACKGROUND: Parkinson's disease (PD) is an extrapyramidal movement disorder associated with a hypokinetic condition generated by impairment in dopaminergic neuronal viability in the nigrostriatal region of the brain. Current medications can only provide symptomatic management; to date, no permanent cure is available. To compensate for this lacuna, researchers are gaining interest in antigen-based therapy, and Bacille-Calmette-Guerin (BCG) is one of the vaccines with a high safety margin that acts by stimulating immunoreactive T-cells in the CNS and reducing expression of pro-inflammatory cytokines including interleukin (IL)-1ß and tumor necrotic factor (TNF-α) to produce neuroprotection. A previous study reported that BCG exerts a neuroprotective effect against several neurodegenerative disorders, such as Alzheimer's disease. OBJECTIVE: The objective of this study is to explore the neuroprotective effect of the BCG vaccine against the rotenone model of PD. METHODS: Rotenone (1.5 mg/kg, s.c) for 28 days, and BCG vaccine (2 × 107 cfu, i.p) single dose was injected to rats, and behavioral assessments were performed on the 21st and 28th day. On the 29th day, rats were sacrificed, and brains were isolated for biochemical and neurochemical estimation. RESULTS: BCG vaccine significantly restored rotenone-induced motor deficits (open field test, narrow beam walk, and rotarod), biochemical levels (GSH, SOD, catalase, MDA, and nitrite), neurotransmitters (dopamine, 5-hydroxy tryptamine, norepinephrine, 3,4-dihydroxyphenylacetic acid, hemovanillic acid, and 5-hydroxy indoleacetic acid), and levels of inflammatory cytokines (IL-1ß and TNF-α) in the striatum. It also prevents histopathological changes by reducing eosinophilic lesions in the striatum. CONCLUSION: From the results, we conclude that BCG vaccine showed neuroprotection through antioxidant and anti-inflammatory effect. Thus, in the future, it can be used as a neuroprotective agent for other neurological disorders, including PD.

Opportunities and challenges in application of artificial intelligence in pharmacology.

Artificial intelligence (AI) is a machine science that can mimic human behaviour like intelligent analysis of data. AI functions with specialized algorithms and integrates with deep and machine learning. Living in the digital world can generate a huge amount of medical data every day. Therefore, we need an automated and reliable evaluation tool that can make decisions more accurately and faster. Machine learning has the potential to learn, understand and analyse the data used in healthcare systems. In the last few years, AI is known to be employed in various fields in pharmaceutical science especially in pharmacological research. It helps in the analysis of preclinical (laboratory animals) and clinical (in human) trial data. AI also plays important role in various processes such as drug discovery/manufacturing, diagnosis of big data for disease identification, personalized treatment, clinical trial research, radiotherapy, surgical robotics, smart electronic health records, and epidemic outbreak prediction. Moreover, AI has been used in the evaluation of biomarkers and diseases. In this review, we explain various models and general processes of machine learning and their role in pharmacological science. Therefore, AI with deep learning and machine learning could be relevant in pharmacological research.

Yoga-Based Cardiac Rehabilitation After Acute Myocardial Infarction: A Randomized Trial.

BACKGROUND: Given the shortage of cardiac rehabilitation (CR) programs in India and poor uptake worldwide, there is an urgent need to find alternative models of CR that are inexpensive and may offer choice to subgroups with poor uptake (e.g., women and elderly). OBJECTIVES: This study sought to evaluate the effects of yoga-based CR (Yoga-CaRe) on major cardiovascular events and self-rated health in a multicenter randomized controlled trial. METHODS: The trial was conducted in 24 medical centers across India. This study recruited 3,959 patients with acute myocardial infarction with a median and minimum follow-up of 22 and 6 months. Patients were individually randomized to receive either a Yoga-CaRe program (n = 1,970) or enhanced standard care involving educational advice (n = 1,989). The co-primary outcomes were: 1) first occurrence of major adverse cardiovascular events (MACE) (composite of all-cause mortality, myocardial infarction, stroke, or emergency cardiovascular hospitalization); and 2) self-rated health on the European Quality of Life-5 Dimensions-5 Level visual analogue scale at 12 weeks. RESULTS: MACE occurred in 131 (6.7%) patients in the Yoga-CaRe group and 146 (7.4%) patients in the enhanced standard care group (hazard ratio with Yoga-CaRe: 0.90; 95% confidence interval [CI]: 0.71 to 1.15; p = 0.41). Self-rated health was 77 in Yoga-CaRe and 75.7 in the enhanced standard care group (baseline-adjusted mean difference in favor of Yoga-CaRe: 1.5; 95% CI: 0.5 to 2.5; p = 0.002). The Yoga-CaRe group had greater return to pre-infarct activities, but there was no difference in tobacco cessation or medication adherence between the treatment groups (secondary outcomes). CONCLUSIONS: Yoga-CaRe improved self-rated health and return to pre-infarct activities after acute myocardial infarction, but the trial lacked statistical power to show a difference in MACE. Yoga-CaRe may be an option when conventional CR is unavailable or unacceptable to individuals. (A study on effectiveness of YOGA based cardiac rehabilitation programme in India and United Kingdom; CTRI/2012/02/002408).

Effectiveness and cost-effectiveness of a Yoga-based Cardiac Rehabilitation (Yoga-CaRe) program following acute myocardial infarction: Study rationale and design of a multi-center randomized controlled trial.

BACKGROUND: Cardiac rehabilitation (CR) is a standard treatment for secondary prevention of acute myocardial infarction (AMI) in high income countries (HICs), but it is inaccessible to most patients in India due to high costs and skills required for multidisciplinary CR teams. We developed a low-cost and scalable CR program based on culturally-acceptable practice of yoga (Yoga-CaRe). In this paper, we report the rationale and design for evaluation of its effectiveness and cost-effectiveness. METHODS: This is a multi-center, single-blind, two-arm parallel-group randomized controlled trial across 22 cardiac care hospitals in India. Four thousand patients aged 18-80 years with AMI will be recruited and randomized 1:1 to receive Yoga-CaRe program (13 sessions supervised by an instructor and encouragement to self-practice daily) or enhanced standard care (3 sessions of health education) delivered over a period of three months. Participants will be followed 3-monthly till the end of the trial. The co-primary outcomes are a) time to occurrence of first cardiovascular event (composite of all-cause mortality, non-fatal myocardial infarction, non-fatal stroke and emergency cardiovascular hospitalization), and b) quality of life (Euro-QoL-5L) at 12 weeks. Secondary outcomes include need for revascularization procedures, return to pre-infarct activities, tobacco cessation, medication adherence, and cost-effectiveness of the intervention. CONCLUSION: This trial will alone contribute >20% participants to existing meta-analyses of randomized trials of CR worldwide. If Yoga-CaRe is found to be effective, it has the potential to save millions of lives and transform care of AMI patients in India and other low and middle income country settings.