Yoga Programme for Type 2 Diabetes Prevention (YOGA-DP): A Qualitative Study Exploring the Trial Team’s Facilitators and Challenges in Conducting a Feasibility Trial in India

BACKGROUND: In India, around 77 million people are at high risk of developing type 2 diabetes mellitus (T2DM). Yoga interventions can be effective in preventing T2DM. We conducted a feasibility randomized controlled trial (RCT) in India, and the intervention was the Yoga Programme for T2DM Prevention (YOGA-DP). This study aimed to identify and explore the facilitators and challenges in conducting the feasibility trial in India, and more specifically, to explore the perceptions and experiences of trial staff in relation to running the feasibility trial and Yoga instructors in relation to delivering the intervention. METHODS: An exploratory qualitative study was conducted at two trial sites in India (Yoga centers in New Delhi and Bengaluru). Semi-structured interviews were conducted with ten participants (six trial staff and four Yoga instructors) to explore their perceptions and experiences related to the study's aim. Data were analyzed using deductive as well as inductive logic and an interpretative phenomenological approach. RESULTS: Feasibility-trial-related facilitators were useful participant recruitment strategies and help and support received from the trial coordination center. Intervention-related facilitators were strengths of the intervention content, structure, and delivery (including materials) and competencies of Yoga instructors. Feasibility-trial-related challenges were lack of awareness about T2DM among potential participants, stigma and fear associated with T2DM among potential participants, difficulties in explaining the research and obtaining written informed consent from potential participants, expectations and demands of potential participants and control-group participants, gender and language issues in participant recruitment, other participant recruitment-related challenges, issues in participant follow-up, and issues in data collection and trial documentation. Intervention-related challenges were the limited interest of participants in Yoga, participants' time constraints on practicing Yoga, participants' health issues hindered Yoga practice, beginners' difficulties with practicing Yoga, participants' demotivation to practice Yoga at home, issues with the Yoga practice venue, confusion regarding the intervention structure, issues with intervention materials, and the incompetence of Yoga instructors. CONCLUSIONS: The perceptions and experiences of trial staff and Yoga instructors helped us to understand the facilitators and challenges in running a feasibility trial and delivering the intervention for T2DM prevention, respectively. These findings and their suggestions will be used when designing the definitive RCT for evaluating YOGA-DP's effectiveness, and may be helpful to researchers planning similar trials. TRIAL REGISTRATION NUMBER: India (CTRI) CTRI/2019/05/018893

Tau and mTOR: The Hotspots for Multifarious Diseases in Alzheimer's Development

The hyperphosphorylation of tau protein and the overexpression of mTOR are considered to be the driving force behind Aβ plaques and Neurofibrillay Tangles (NFT's), hallmarks of Alzheimer's disease (AD). It is now evident that miscellaneous diseases such as Diabetes, Autoimmune diseases, Cancer, etc. are correlated with AD. Therefore, we reviewed the literature on the causes of AD and investigated the association of tau and mTOR with other diseases. We have discussed the role of insulin deficiency in diabetes, activated microglial cells, and dysfunction of blood-brain barrier (BBB) in Autoimmune diseases, Presenilin 1 in skin cancer, increased reactive species in mitochondrial dysfunction and deregulated Cyclins/CDKs in promoting AD pathogenesis. We have also discussed the possible therapeutics for AD such as GSK3 inactivation therapy, Rechaperoning therapy, Immunotherapy, Hormonal therapy, Metal chelators, Cell cycle therapy, γ-secretase modulators, and Cholinesterase and BACE 1-inhibitors which are thought to serve a major role in combating pathological changes coupled with AD. Recent research about the relationship between mTOR and aging and hepatic Aβ degradation offers possible targets to effectively target AD. Future prospects of AD aims at developing novel drugs and modulators that can potentially improve cell to cell signaling, prevent Aβ plaques formation, promote better release of neurotransmitters and prevent hyperphosphorylation of tau

Yoga Programme for Type 2 Diabetes Prevention (YOGA-DP): a qualitative study exploring trial team’s facilitators and challenges in conducting a feasibility trial in India

BACKGROUND: In India, around 77 million people are at high risk of developing type 2 diabetes mellitus (T2DM). Yoga interventions can be effective in preventing T2DM. We conducted a feasibility randomized controlled trial (RCT) in India, and the intervention was the Yoga Programme for T2DM Prevention (YOGA-DP). This study aimed to identify and explore the facilitators and challenges in conducting the feasibility trial in India, and more specifically, to explore the perceptions and experiences of trial staff in relation to running the feasibility trial and Yoga instructors in relation to delivering the intervention. METHODS: An exploratory qualitative study was conducted at two trial sites in India (Yoga centers in New Delhi and Bengaluru). Semi-structured interviews were conducted with ten participants (six trial staff and four Yoga instructors) to explore their perceptions and experiences related to the study's aim. Data were analyzed using deductive as well as inductive logic and an interpretative phenomenological approach. RESULTS: Feasibility-trial-related facilitators were useful participant recruitment strategies and help and support received from the trial coordination center. Intervention-related facilitators were strengths of the intervention content, structure, and delivery (including materials) and competencies of Yoga instructors. Feasibility-trial-related challenges were lack of awareness about T2DM among potential participants, stigma and fear associated with T2DM among potential participants, difficulties in explaining the research and obtaining written informed consent from potential participants, expectations and demands of potential participants and control-group participants, gender and language issues in participant recruitment, other participant recruitment-related challenges, issues in participant follow-up, and issues in data collection and trial documentation. Intervention-related challenges were the limited interest of participants in Yoga, participants' time constraints on practicing Yoga, participants' health issues hindered Yoga practice, beginners' difficulties with practicing Yoga, participants' demotivation to practice Yoga at home, issues with the Yoga practice venue, confusion regarding the intervention structure, issues with intervention materials, and the incompetence of Yoga instructors. CONCLUSIONS: The perceptions and experiences of trial staff and Yoga instructors helped us to understand the facilitators and challenges in running a feasibility trial and delivering the intervention for T2DM prevention, respectively. These findings and their suggestions will be used when designing the definitive RCT for evaluating YOGA-DP's effectiveness, and may be helpful to researchers planning similar trials. TRIAL REGISTRATION NUMBER: India (CTRI) CTRI/2019/05/018893

Feasibility Trial of Yoga Programme for Type 2 Diabetes Prevention (YOGA-DP) among High-Risk People in India: A Qualitative Study to Explore Participants' Trial- and Intervention-Related Barriers and Facilitators.

Yoga-based interventions can be effective in preventing type 2 diabetes mellitus (T2DM). We developed a Yoga programme for T2DM prevention (YOGA-DP) and conducted a feasibility randomised controlled trial (RCT) among high-risk people in India. This qualitative study's objective was to identify and explore participants' trial- and intervention-related barriers and facilitators. The feasibility trial was conducted at two Yoga centres in New Delhi and Bengaluru, India. In this qualitative study, 25 trial participants (13 intervention group, 12 control group) were recruited for semi-structured interviews. Data were analysed using deductive logic and an interpretative phenomenological approach. Amongst intervention and control participants, key barriers to trial participation were inadequate information about recruitment and randomisation processes and the negative influence of non-participants. Free blood tests to aid T2DM prevention, site staff's friendly behaviour and friends' positive influence facilitated trial participation. Amongst intervention participants, readability and understanding of the programme booklets, dislike of the Yoga diary, poor quality Yoga mats, difficulty in using the programme video, household commitment during home sessions, unplanned travel, difficulty in practising Yoga poses, hesitation in attending programme sessions with the YOGA-DP instructor of the opposite sex and mixed-sex group programme sessions were key barriers to intervention participation. Adequate information was provided on T2DM prevention and self-care, good venue and other support provided for programme sessions, YOGA-DP instructors' positive behaviour and improvements in physical and mental well-being facilitated intervention participation. In conclusion, we identified and explored participants' trial- and intervention-related barriers and facilitators. We identified an almost equal number of barriers (n = 12) and facilitators (n = 13); however, intervention-related barriers and facilitators were greater than for participating in the trial. These findings will inform the design of the planned definitive RCT design and intervention and can also be used to design other Yoga interventions and RCTs

Yoga programme for type 2 diabetes prevention (YOGA-DP) among high-risk people in India: a multi-center feasibility randomized controlled trial

IntroductionMany Indians are at high-risk of type 2 diabetes mellitus (T2DM). The blood glucose level can be improved through a healthy lifestyle (such as physical activity and a healthy diet). Yoga can help in T2DM prevention, being a culturally appropriate approach to improving lifestyle. We developed a Yoga programme for T2DM prevention (YOGA-DP), a 24-week structured lifestyle education and exercise (Yoga) program that included 27 group Yoga sessions and self-practice of Yoga at home. In this study, the feasibility of undertaking a definitive randomized controlled trial (RCT) was explored that will evaluate the intervention’s effectiveness among high-risk individuals in India. MethodsA multi-center, two-arm, parallel-group, feasibility RCT was conducted in India. The outcome assessors and data analysts were blinded. Adults with a fasting blood glucose level of 100-125 mg/dL (i.e., at high-risk of T2DM) were eligible. Participants were randomized centrally using a computer-generated randomization schedule. In the intervention group, participants received YOGA-DP. In the control group, participants received enhanced standard care. ResultsIn this feasibility trial, the recruitment of participants took 4 months (from May to September 2019). We screened 711 people and assessed 160 for eligibility. Sixty-five participants (33 in the intervention group and 32 in the control group) were randomized, and 57 (88%) participants were followed up for 6 months (32 in the intervention group and 25 in the control group). In the intervention group, the group Yoga sessions were continuously attended by 32 (97%) participants (median (interquartile range (IQR)) number of sessions attended = 27 (3)). In the intervention group, Yoga was self-practiced at home by 30 (91%) participants (median (IQR) number of days/week and minutes/day self-practiced = 2 (2) and 35 (15), respectively). In the control group, one (3%) participant attended external Yoga sessions (on Pranayama) for one week during the feasibility trial period. There was no serious adverse event.ConclusionsThe participant recruitment and follow-up and adherence to the intervention were promising in this feasibility study. In the control group, the potential contamination was low. Therefore, it should be feasible to undertake a definitive RCT in the future that will evaluate YOGA-DP’s effectiveness among high-risk people in India

Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes

Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes, although how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes monoubiquitination in a conserved polybasic domain. Stx3 present at the basolateral—but not the apical—plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A nonubiquitinatable mutant of Stx3 (Stx3-5R) fails to enter this pathway and leads to the inability of the apical exosomal cargo protein GPRC5B to enter the ILV/exosomal pathway. This suggests that ubiquitination of Stx3 leads to removal from the basolateral membrane to achieve apical polarity, that Stx3 plays a role in the recruitment of cargo to exosomes, and that the Stx3-5R mutant acts as a dominant-negative inhibitor. Human cytomegalovirus (HCMV) acquires its membrane in an intracellular compartment and we show that Stx3-5R strongly reduces the number of excreted infectious viral particles. Altogether these results suggest that Stx3 functions in the transport of specific proteins to apical exosomes and that HCMV exploits this pathway for virion excretion

Nations within a nation: variations in epidemiological transition across the states of India, 1990–2016 in the Global Burden of Disease Study

18% of the world's population lives in India, and many states of India have populations similar to those of large countries. Action to effectively improve population health in India requires availability of reliable and comprehensive state-level estimates of disease burden and risk factors over time. Such comprehensive estimates have not been available so far for all major diseases and risk factors. Thus, we aimed to estimate the disease burden and risk factors in every state of India as part of the Global Burden of Disease (GBD) Study 2016

Quantum chemical study of infrared and Raman spectra of dicyanodiacetylene

162-167Structural and vibrational spectral features of dicyanodiacetylene, a molecule of considerable interstellar significance, using ab-initio (MP2) and density functional theory (DFT) based quantum chemical methods have been studied. Double and triple-zeta basis sets with polarization and diffuse functions (6-31G**, 6-311+G**) as well as Dunning’s correlation consistent basis sets (cc-pvDZ, cc-pvTZ and aug cc-pvTZ) have been used in the study. Optimized geometry, infrared and Raman spectra have been calculated and a complete vibrational assignment based on potential energy distribution along the internal coordinates and depolarization ratios of the Raman bands has been provided. Dicyanodiacetylene is found to be a symmetric linear chain molecule of D∞h symmetry having significant conjugation in the chain. This affects the length of both the single and triple bonds. Conjugation effect is most pronounced for the central C-C bond which has a length of about 1.35Å. While some of the earlier assignments to the infrared and Raman bands have been confirmed, several new assignments have been suggested using symmetry considerations and position, intensity and polarization of the vibrational bands

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Not AvailableA positive association between oxidative stress and hyper-thyroid conditions is well established. Vitamin E (VIT-E) and curcumin (CRM) are considered as potent antioxidant small molecules. Nuclear factor erythroid 2–related factor 2(NRF-2) is known to bind with antioxidant response element and subsequently activate expression of antioxidant enzymes. However, the activation of NRF-2 depends on removal of its regulator Kelch-like ECH-associated protein 1(NRF-2). In the current study, an attempt is made to demonstrate whether effects of VIT-E and CRM are due to direct interaction with the target proteins (i.e. NRF-2, NRF-2, SOD, catalase and LDH) or by possible interaction with the flanking region of their promoters by in silico analysis. Further, these results were corroborated by pretreatment of H9C2 cells (1 x 106 cells per mL of media) with VIT-E (50 lM) and/or CRM (20 lM) for 24 h followed by induction of oxidative stress via T4 (100 nm) administration and assaying the active oxygen metabol ism. Discriminant function analyses (DFA) indicated that T4 has a definite role in increasing oxidative stress as evidenced by induction of ROS generation, increase in mitochondrial membrane potential and elevated lipid peroxidation (LPx). Pretreatment with the two antioxidants have ameliorative effects more so when given in combination. The decline in biological activities of the principal antioxidant enzymes SOD and CAT with respect to T4 treatment and its restoration in antioxidant pretreated group further validated our in silico data.Not Availabl