Effect of wire diameter and extent of wire composite splint on the mobility of luxated and anchor primary teeth: A typodont study.

BACKGROUND/AIMS: The recommendations for splinting are well established for the injuries of permanent dentition; however, ambiguity still exists for the injuries in primary dentition. Hence, this study aimed to determine the most appropriate dimensions of stainless steel wire and its extent, for achieving the physiologic mobility in primary dentition. MATERIAL AND METHODS: This study was designed as an in vitro experiment by using a typodont model of primary dentition. The baseline mobility of primary maxillary incisors was calibrated to the physiologic mobility of natural primary incisors by using a Teflon tape wrapped around the roots of resin teeth. Splinting was done using a stainless steel wire of 0.2 mm (Group I), 0.3 mm (Group II), and 0.4 mm (Group III). These groups were subdivided (a, b, and c) on the basis of the extent of the splint, and pre splint mobility (Pre-PV) and post-splint mobility (Post-PV) were tested by Periotest M. The splint effect was calculated by subtracting Post-PVs and Pre-PVs. RESULTS: The normal values of mobility in healthy human volunteers ranged from 10.5 to 13. The overall splint effect was higher in Group III irrespective of the extent of the splint, whereas it was found to be the lowest in Group I (b and c). The splint effect increased with the extent of the splint in all the groups. Among all the groups, the splint effect on the anchor teeth was observed to increase with the extent of the splint and the diameter of the wire. CONCLUSION: The mobility of the injured and anchor teeth splinted with 0.2-mm stainless steel wire was similar to the pre-splint and physiologic mobility. The most favorable extension was one tooth adjacent to the injured tooth on each side for both 0.2- and 0.3-mm wires.

Quality analysis of the clinical practice guidelines for management of impacted maxillary central incisors: a systematic review.

PURPOSE: To assess the quality of clinical practice guidelines (CPG) for management of impacted central incisors. METHODS: Search was performed in PubMed, LILACS, Web of Science, EMBASE, Scopus, and Cochrane databases, and guideline-focused databases/repositories on 15-09-2022 without any limitations and was updated on 15-07-2023. Grey literature search was also performed. Two independent reviewers were involved in the study selection and data extraction. Quality assessment of the included CPG was performed by four independent appraisers using the AGREE-II instrument. The degree of agreement among the appraisers was calculated using the intraclass correlation coefficient (ICC). RESULTS: Five CPG were included in the review. The Ministry of Health, Malaysia (MHM) guideline obtained the highest scores in all six domains of AGREE-II and an overall score of 73% demonstrating the "highest" quality. The remaining four guidelines obtained overall "low-quality" scores ranging from 34.57-37.52%. The ICC scores ranged from 0.530 to 0.990 for various domains of AGREE-II. CONCLUSION: MHM guidelines demonstrated high-quality scores in domains of 'scope and purpose', 'clarity of presentation', 'applicability domain', and 'editorial independence', while others were found to have moderate or low quality. This review identified areas that can be addressed by future guideline developers to avoid these discrepancies.

Correction: Luteolin-mediated Kv1.3 K+ channel inhibition augments BCG vaccine efficacy against tuberculosis by promoting central memory T cell responses in mice.

[This corrects the article DOI: 10.1371/journal.ppat.1008887.].

Radiation response of Y3Al5O12 and Nd3+-Y3Al5O12 to Swift heavy ions: insight into structural damage and defect dynamics.

Understanding the behavior of a material under irradiation is paramount to its application in the nuclear industry. The present work explores the radiation response of garnet Y3Al5O12 (YAG) and Nd3+-substituted Y3Al5O12 (Nd-YAG) under a 100 MeV Iodine beam at varying fluences to mimic the effect of fission fragments. This is relevant to the potential application of garnet as a host for minor actinide (MA) transmutation (Nd3+: surrogate for long-lived MA (Am3+, Np3+, Cm3+)). The un-irradiated and irradiated YAG and Nd-YAG samples were investigated by X-ray diffraction and Raman spectroscopy. Positron annihilation spectroscopy, thermal spike modelling and theoretical studies have been employed to understand the role of substitution and defect energetics in influencing this radiation response. Although both materials were not completely amorphized under the present irradiation conditions, a tremendous loss in crystallinity could be observed with increase in fluence, the damage being much more in Nd-YAG. Ion track radii of 2.17 nm and 2.91 nm were estimated for YAG and Nd-YAG respectively. Thermal-spike calculations show an increase in radiation-induced transient temperatures upon Nd-substitution that causes greater radiation damage in Nd-YAG. The enhancement in radiation-induced damage with increasing ion-fluence manifests in broadening and weakening of the Raman modes and XRD peaks. An increase in the average positron annihilation lifetime indicated the creation of oxygen vacancies. The defect formation energies of Y3Al5O12 have been theoretically estimated via density functional theory (DFT) and unfavorable energies required for creating cation pair anti-sites have been proposed as one of the possible reasons for the relatively poorer radiation response of YAG. The irradiation behavior of Y3Al5O12 has been compared with disordered fluorite (YSZ) and zirconate pyrochlores, which are well-researched ceramics for MA transmutation.

Effect of low-level laser therapy plus exercise therapy on pain, range of motion, muscle strength, and function in knee osteoarthritis - a systematic review and meta-analysis.

BACKGROUND: Knee osteoarthritis (KOA) is commonly associated with multiple musculoskeletal impairments. OBJECTIVE: The purpose of this review was (1) to investigate the effectiveness of LLLT plus ET on pain, ROM, muscle strength, and function in KOA immediately after therapy and (2) whether the effectiveness of LLLT plus ET could be sustained at follow-up (4 - 32 weeks). METHODS: Six databases were systematically searched upto December 2021 to find relevant articles. Included studies were RCTs written in English, which compared LLLT plus ET with placebo LLLT plus ET in KOA. Three independent reviewers extracted data and assessed the quality of included studies. Standard mean difference (SMD) was used in meta-analysis using random effect model. RESULT: Of the 6307 articles, 14 RCTs (820 patients) met the inclusion criteria. The results demonstrated that there was a significant difference in pain immediately after therapy (SMD: -0.58, p = 0.001) and at follow-up (SMD: -1.35, p = 0.05) in LLLT plus ET group. There were no significant differences in knee ROM, muscle strength, and knee function outcomes immediately and at follow-up. CONCLUSION: Our findings indicate that LLLT plus ET could be considered to alleviate pain in the KOA. LLLT reduces pain at 4-8J with a wavelength of 640-905nm per point applied for 10-16 sessions at a frequency of 2 sessions/week. An exercise therapy program at prescribed dosage involving major muscle groups might help. However, LLLT plus ET is no more effective than placebo LLLT plus ET in improving ROM, muscle strength, and function in KOA.

Blood flow restriction therapy with exercise are no better than exercise alone in improving athletic performance, muscle strength, and hypertrophy: a systematic review and meta-analysis.

BACKGROUND: The benefits of Blood Flow Restriction Therapy (BFRT) have gained attention in recent times. OBJECTIVE: This review aimed to evaluate the immediate (up to 24 hours), intermediate (up to 6 weeks), and long term (6-10 weeks) effects of BFRT plus exercises (EX) compared to EX only on athletic performance (sprint and jump performance), muscle strength, and hypertrophy in athletes and physically active population. METHODS: A literature search was conducted to select randomized controlled trials across four electronic databases from inception till April 2021. The search yielded twenty-seven studies in total. RESULTS: Based on eligibility criteria, twenty-one studies were analyzed. No differences were found between both groups for immediate (standardized mean difference [SMD] -0.02, 95% confidence interval [CI] -0.31, 0.27) and long-term effects (SMD -0.30, 95%CI -0.90, 0.30) on sprint performance. For jump performance, no significant effect was observed immediately (SMD -0.02 (95% CI -1.06, 1.02) and long term (SMD -0.40 (95% CI -1.46, 0.67). Similarly, muscle torque at intermediate (SMD 0.90 (95% CI -1.01, 2.81) and long term (SMD -0.54 (95% CI -1.19, 0.12), muscle strength at intermediate (SMD 1.12 (95% CI 0.20, 2.04) , and long term (SMD -0.07 (95% CI -0.56, 0.42) also showed non-significant effects. Muscle hypertrophy at intermediate (SMD 0.16 (95% CI -0.31, 0.63) and long term (SMD -0.20 (95% CI -0.90, 0.50) were not statistically significant. CONCLUSIONS: There was no significant difference observed in BFRT plus EX group compared to the EX-group on athletic performance, muscle strength, and muscle hypertrophy.

Effects of circadian rhythm on anaerobic performance and blood lactate level: a systematic review.

PURPOSE: Circadian rhythm affects maximal short-term performance, and it is an important determinant of the training component. This review aimed to summarise the influence of circadian rhythm on peak and mean power output of muscle, fatigue index, and blood lactate levels. METHODS: English language articles were searched through the following databases: PubMed, Web of Science, Science Direct, and Google Scholar, and pertinent randomized control trials were scrutinized. RESULTS: The search revealed 17,481 articles, and 29 were included in this systematic review based on inclusion and exclusion criteria. Randomized control trials were selected, and the methodological validity of articles was evaluated using the 'Cochrane risk of bias tool'. Findings suggest that outcome variables muscle peak power output (p < 0.0001, Z = 7.22, I2 = 57.42, SMD = - 0.91, 95% confidence interval CI = - 1.16, - 0.67), muscle mean power output (p < 0.0001, Z = 5.66, I2 = 83.85, SMD = - 0.75, 95% CI = - 1.01, - 0.49), and fatigue index (p = 0.02, Z = 2.41, I2 = 2.49, SMD = - 0.39, 95% CI = - 0.72, - 0.07) were higher in the evening while the level of blood lactate was higher in the morning (p = 0.79, Z = 0.27, I2 = 0.73, SMD = - 0.05, 95% CI = - 0.46, - 0.35). CONCLUSION: The results show that diurnal variation affects both peak and mean power output of muscle as well as fatigue index. However, there is no remarkable effect of circadian rhythm on blood lactate level. A major factor attributed to this finding was the variation in the training experience of participants. For an effective training prescription, it is very important to consider the effect of the biological clock on muscle power output since anaerobic exercise performance is discernibly influenced by the time of the day.

Organ-On-A-Chip Models of the Blood-Brain Barrier: Recent Advances and Future Prospects.

The human brain and central nervous system (CNS) present unique challenges in drug development for neurological diseases. One major obstacle is the blood-brain barrier (BBB), which hampers the effective delivery of therapeutic molecules into the brain while protecting it from blood-born neurotoxic substances and maintaining CNS homeostasis. For BBB research, traditional in vitro models rely upon Petri dishes or Transwell systems. However, these static models lack essential microenvironmental factors such as shear stress and proper cell-cell interactions. To this end, organ-on-a-chip (OoC) technology has emerged as a new in vitro modeling approach to better recapitulate the highly dynamic in vivo human brain microenvironment so-called the neural vascular unit (NVU). Such BBB-on-a-chip models have made substantial progress over the last decade, and concurrently there has been increasing interest in modeling various neurological diseases such as Alzheimer's disease and Parkinson's disease using OoC technology. In addition, with recent advances in other scientific technologies, several new opportunities to improve the BBB-on-a-chip platform via multidisciplinary approaches are available. In this review, an overview of the NVU and OoC technology is provided, recent progress and applications of BBB-on-a-chip for personalized medicine and drug discovery are discussed, and current challenges and future directions are delineated.

Luteolin-mediated Kv1.3 K+ channel inhibition augments BCG vaccine efficacy against tuberculosis by promoting central memory T cell responses in mice.

Despite the availability of multiple antibiotics, tuberculosis (TB) remains a major health problem worldwide, with one third of the population latently infected and ~2 million deaths annually. The only available vaccine for TB, Bacillus Calmette Guérin (BCG), is ineffective against adult pulmonary TB. Therefore, alternate strategies that enhance vaccine efficacy are urgently needed. Vaccine efficacy and long-term immune memory are critically dependent on central memory T (TCM) cells, whereas effector memory T (TEM) cells are important for clearing acute infections. Recently, it has been shown that inhibition of the Kv1.3 K+ ion channel, which is predominantly expressed on TEM but not TCM cells, profoundly enhances TCM cell differentiation. We exploited this phenomenon to improve TCM:TEM cell ratios and protective immunity against Mycobacterium tuberculosis infection in response to BCG vaccination of mice. We demonstrate that luteolin, a plant-derived Kv1.3 K+ channel inhibitor, profoundly promotes TCM cells by selectively inhibiting TEM cells, and significantly enhances BCG vaccine efficacy. Thus, addition of luteolin to BCG vaccination may provide a sustainable means to improve vaccine efficacy by boosting host immunity via modulation of memory T cell differentiation.

Predictors of smokeless tobacco use among the adult population of north-east India during 2009-2017: A decomposition analysis.

Background & objectives: Contrary to overall declining trend in smokeless tobacco (SLT) use in India, an increase is observed in north-east (NE) India. This study examined the predictors of daily SLT use by gender and assessed the demographic and socio-economic characteristics that contribute to gender differences in SLT use in NE India. Methods: Data collected from 15,259 and 13,574 adults in the two rounds of Global Tobacco Adult Survey 1 and 2 for NE India during 2009-2010 and 2016-2017 were analyzed. Relative change, multivariable binary logistic regression and Blinder-Oaxaca decomposition analysis were used for analysis. Results: The findings suggest that among women in NE India, the daily SLT use significantly increased by 58 per cent between 2009-2010 to 2016-2017. Women residing in Nagaland, Manipur, Mizoram and Tripura were 3.5 and 2.5 times, respectively more likely to be daily SLT users compared to those in Assam. While age, education and wealth were the significant predictors of SLT use in both women and men, increased odds of SLT use were observed with women's type of occupation and the State of residence. The majority of the gender differences in daily SLT use was explained by differences in work status (44%), age (26%), education (14%) and wealth status (9%) between men and women. Interpretation & conclusions: Increasing prevalence of SLT use amongst women in the NE States necessitates integration of gender-specific messages on harmful effects of SLT in the ongoing tobacco control programmes and development of culturally appropriate community-based interventions for cessation of SLT use.

Development & validation of scales to assess stigma related to COVID-19 in India.

Background & objectives: COVID-19 pandemic has triggered social stigma towards individuals affected and their families. This study describes the process undertaken for the development and validation of scales to assess stigmatizing attitudes and experiences among COVID-19 and non-COVID-19 participants from the community. Methods: COVID-19 Stigma Scale and Community COVID-19 Stigma Scale constituting 13 and six items, respectively, were developed based on review of literature and news reports, expert committee evaluation and participants' interviews through telephone for a multicentric study in India. For content validity, 61 (30 COVID-19-recovered and 31 non-COVID-19 participants from the community) were recruited. Test-retest reliability of the scales was assessed among 99 participants (41 COVID-19 recovered and 58 non-COVID-19). Participants were administered the scale at two-time points after a gap of 7-12 days. Cronbach's alpha, overall percentage agreement and kappa statistics were used to assess internal consistency and test-retest reliability. Results: Items in the scales were relevant and comprehensible. Both the scales had Cronbach's α above 0.6 indicating moderate-to-good internal consistency. Test-retest reliability assessed using kappa statistics indicated that for the COVID-19 Stigma Scale, seven items had a moderate agreement (0.4-0.6). For the Community COVID-19 Stigma Scale, four items had a moderate agreement. Interpretation & conclusions: Validity and reliability of the two stigma scales indicated that the scales were comprehensible and had moderate internal consistency. These scales could be used to assess COVID-19 stigma and help in the development of appropriate stigma reduction interventions for COVID-19 infected, and mitigation of stigmatizing attitudes in the community.

Functional insights into Mycobacterium tuberculosis DevR-dependent transcriptional machinery utilizing Escherichia coli.

DevR/DosR response regulator is believed to participate in virulence, dormancy adaptation and antibiotic tolerance mechanisms of Mycobacterium tuberculosis by regulating the expression of the dormancy regulon. We have previously shown that the interaction of DevR with RNA polymerase is essential for the expression of DevR-regulated genes. Here, we developed a M. tuberculosis-specific in vivo transcription system to enrich our understanding of DevR-RNA polymerase interaction. This in vivo assay involves co-transforming E. coli with two plasmids that express α, ß, ß' and σA subunits of M. tuberculosis RNA polymerase and a third plasmid that harbors a DevR expression cassette and a GFP reporter gene under the DevR-regulated fdxA promoter. We show that DevR-dependent transcription is sponsored exclusively by M. tuberculosis RNA polymerase and regulated by α and σA subunits of M. tuberculosis RNA polymerase. Using this E. coli triple plasmid system to express mutant variants of M. tuberculosis RNA polymerase, we identified E280 residue in C-terminal domain of α and K513 and R515 residues of σA to participate in DevR-dependent transcription. In silico modeling of a ternary complex of DevR, σA domain 4 and fdxA promoter suggest an interaction of Q505, R515 and K513 residues of σA with E178 and D172 residues of DevR and E471 of σA, respectively. These findings provide us with new insights into the interactions between DevR and RNA polymerase of M. tuberculosis which can be targeted for intercepting DevR function. Finally, we demonstrate the utility of this system for screening of anti-DevR compounds.

Molecular mechanisms of cognitive impairment associated with stroke.

Stroke is the second leading cause of death after coronary heart disease in developed countries and is the greatest cause of disability and cognitive impairment. Risk factors for cognitive impairment and dementia after stroke are multifactorial including older age, family history, hypertension, arterial fibrillation, diabetes, genetic variants, low educational status, vascular comorbidities, prior transient ischaemic attack or recurrent stroke, depressive illness duration of a stroke, location, volume, intensity, and degree of neuronal degeneration, location and size of infarction after stroke, time interval after stroke other cerebral dysfunctions. The pathophysiology of stroke associated cognitive impairment is complex and recent molecular, cellular, and animal models studies have revealed that multiple cellular changes have been implicated, including altered redox state, mitochondrial dysfunction, disruption of the blood-brain barrier, perivascular spacing, glymphatic system impairment, microglia activation and amyloid-ß deposition in the parenchyma of the brain. These studies have also evidenced the involvement of various transcription factors, intracellular adhesion molecules, and endogenous growth factors in the pathogenesis of cognitive impairment associated with stroke and providing scope for developing therapeutic strategies for treatment. This review summarizes the latest research findings on molecular mechanisms involved in cognitive impairment associated with stroke.

Dose-response and temporal ergogenic effects of ginseng supplementation in athletes and active participants: A systematic review and meta-analysis.

This review sought to assess the dose-response, i.e., low (<300 mg/day) and high (>300 mg/day), and temporal effects of ginseng, i.e., immediate, short-term (up to 4 weeks) and long-term (>4 weeks) in comparison to placebo on physical performance [visual analogue scale (VAS) level, vertical jump(VJ), rating of perceived exertion (RPE), peak power output (PPO)] and physiological measures [VO2 max, creatine kinase(CK), heart rate(HR)], in athletes and active participants. Search in four databases with English language constraints yielded 492 studies. Fourteen studies were shortlisted through PEDro scale by methodological quality evaluation. Ginseng exhibited significant short-term effect at high dosage for VJ improvement (SMD: -8.17, 95% CI: -16.28 to -0.06, p= 0.05). Ginseng had no effect on VAS (SMD: -0.65, 95% CI: -1.35 to 0.06, p= 0.07), RPE (SMD: -1.11, 95% CI: -2.57 to 0.35, p= 0.14), PPO (SMD: -0.70, 95% CI: -1.78 to 0.38, p= 0.20), HR (SMD: -0.54, 95% CI: -2.05 to 0.96, p= 0.48), CK (SMD: 0.33, 95% CI: -0.18 to 0.84, p= 0.21) and VO2 max (SMD: 0.08, 95% CI: -0.69 to 0.85, p= 0.08).The ginseng supplementation was found to have significant short-term effect at high dose only for VJ in athletic and active participants. Methodologically strong research is warranted to further consolidate these findings.

A dissection of Indian growth using a DSGE filter.

In order to build a strong and sustainable recovery post the COVID-19 pandemic, we need to draw important observations from the growth experience of the past. In this context, this paper uses a dynamic stochastic general equilibrium (DSGE) model that takes into account persistent growth rate shocks to decompose the Indian GDP into potential output and output gap. Apart from analysing the trajectory of potential output-output gap, it also examines their underlying drivers. The results suggest that a combined deceleration in neutral and investment-specific technology growth post 2016, brought down the potential growth to around 6 per cent in 2020Q1. The output gap also witnessed a persistent decline since 2018Q1, primarily due to weak demand and a rise in investment adjustment costs reflecting heightened stress in the investment and financial sectors. A forecasting exercise is also undertaken which shows that the estimates of output gap from the model possess competing inflation forecasting ability compared to HP filtered output gap.

COVID-19-associated Pulmonary Aspergillosis: A Case Series.

Background: With the development of coronavirus disease-2019 (COVID-19) pandemic, there is also increased risk of multiple secondary infections either disease- or drug-related. It includes many bacterial as well as invasive fungal infections. Patients and methods: There was suspicion of invasive pulmonary aspergillosis (IPA) infection in COVID-19 patients who were critically ill and had acute respiratory distress syndrome (ARDS). We did radiological evaluation and galactomannan assay in these patients. Result: We have diagnosed COVID-19-associated pulmonary aspergillosis (CAPA) in these patients and started antifungal treatment with voriconazole in all of these COVID-19 patients. Conclusion: It is very important to report such cases, so that healthcare professionals and authorities related to healthcare will be aware of and may also prepare for the increasing burden of this complication. We describe a case series of CAPA infection. How to cite this article: Sharma K, Kujur R, Sharma S, Kumar N, Ray MK. COVID-19-associated Pulmonary Aspergillosis: A Case Series. Indian J Crit Care Med 2022;26(9):1039-1041.

Hemophagocytic lymphohistiocytosis in a child with chronic granulomatous disease: A rare complication of a rare disorder.

Chronic Granulomatous Disease (CGD) is a primary immunodeficiency disorder (PID) of phagocytic cells resulting in failure to eradicate catalase positive microorganisms like Staphylococci and fungal infections; due to deficiency or malfunction of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase subunits in phagocytic leucocytes. We illustrate here one such case; a six year old girl who was admitted in our hospital with history of prolonged fever, non resolving bilateral otitis media and recurrent pneumonia. She was evaluated for an underlying PID and was found to have CGD based on Nitro blue Tetrazolium (NBT) Slide Test and flow cytometric Dihydrorhodamine (DHR) assay. The child was symptomatic despite initial treatment with first-line followed by second-line antibiotics. During the course of current systemic infection, she also developed infection-associated secondary Hemophagocytic Lympho Histiocytosis (HLH) as suggested by her clinical and laboratory parameters. Despite a thorough search, no microorganism could be isolated and so she was treated with empircal antibiotic therapy comprising of meropenem, linezolid and an antifungal. Fever resolved with gradual improvement of laboratory parameters and finally spontaneous resolution of HLH. We conclude that a high index of suspicion for PID is required in a child with recurrent infections. Identification of underlying infectious agent should be attempted to start targeted antimicrobial therapy; both to prevent as well as cure infection associated secondary HLH.

Effects of intra-operative infusion of lidocaine on postoperative pain and quality of recovery in patients undergoing gynecological laparoscopic surgery: A randomized controlled trial.

Background and Aims: Early recovery is desirable after day care surgery. Intravenous lidocaine has anti-inflammatory, anti-hyperalgesic, and analgesic effects and by reducing postoperative pain, nausea, vomiting, and duration of postoperative ileus and hospital stay, might be a useful adjuvant to improve recovery after gynecological laparoscopic surgery. Material and Methods: Fifty female patients, aged 18-55 years, undergoing gynecological laparoscopic surgery were randomly allocated to two groups. In Group L, patients received intravenous lidocaine 1.5 mg/kg at induction of anesthesia followed by infusion of 2 mg/kg/hour until the completion of surgery and in Group NS, patients received normal saline infusion. The Global QoR-40 score at 24 hours, pain score in PACU and at 24 hours, nausea/vomiting, PADSS score in PACU and analgesic consumption over 24 hours were assessed and data were analyzed using SPSS version 17 software. Results: Demographic data were comparable in both groups. The mean Global QoR-40 score in Group L was 197.30 ± 2.3 versus 178.74 ± 6.02 in Group NS (P < 0.001). The mean time to attain PADSS ≥9 was 50 min shorter in Group L than in Group NS (P < 0.001). Nausea, vomiting, and anti-emetic requirement were also significantly reduced in Group L as compared to Group NS (P = 0.005) as was the mean pain score over 24 h (P < 0.001) and the total analgesic consumption over the first 24 h after surgery (P < 0.005). Conclusion: Intraoperative intravenous lidocaine infusion resulted in an improved overall Quality of Recovery in patients undergoing ambulatory gynecological surgery.

Emerging trends from COVID-19 research registered in the Clinical Trials Registry - India.

Since the beginning of the year, the deadly coronavirus pandemic, better known as coronavirus disease 2019 (COVID-19), brought the entire world to an unprecedented halt. In tandem with the global scenario, researchers in India are actively engaged in the conduct of clinical research to counter the pandemic. This review attempts to provide a comprehensive overview of the COVID-19 research in India including design aspects, through the clinical trials registered in the Clinical Trials Registry - India (CTRI) till June 5, 2020. One hundred and twenty two registered trials on COVID-19 were extracted from the CTRI database. These trials were categorized into modern medicine (n=42), traditional medicine (n=67) and miscellaneous (n=13). Of the 42 modern medicine trials, 28 were on repurposed drugs, used singly (n=24) or in combination (n=4). Of these 28 trials, 23 were to evaluate their therapeutic efficacy in different severities of the disease. There were nine registered trials on cell- and plasma-based therapies, two phytopharmaceutical trials and three vaccine trials. The traditional medicine trials category majorly comprised Ayurveda (n=45), followed by homeopathy (n=14) and others (n=8) from Yoga, Siddha and Unani. Among the traditional medicine category, 31 trials were prophylactic and 36 were therapeutic, mostly conducted on asymptomatic or mild-to-moderate COVID-19 patients. This review would showcase the research being conducted on COVID-19 in the country and highlight the research gaps to steer further studies.

Cognate sensor kinase-independent activation of Mycobacterium tuberculosis response regulator DevR (DosR) by acetyl phosphate: implications in anti-mycobacterial drug design.

The DevRS/DosT two-component system is essential for mycobacterial survival under hypoxia, a prevailing stress within granulomas. DevR (also known as DosR) is activated by an inducing stimulus, such as hypoxia, through conventional phosphorylation by its cognate sensor kinases, DevS (also known as DosS) and DosT. Here, we show that the DevR regulon is activated by acetyl phosphate under 'non-inducing' aerobic conditions when Mycobacterium tuberculosis devS and dosT double deletion strain is cultured on acetate. Overexpression of phosphotransacetylase caused a perturbation of the acetate kinase-phosphotransacetylase pathway, a decrease in the concentration of acetyl phosphate and dampened the aerobic induction response in acetate-grown bacteria. The operation of two pathways of DevR activation, one through sensor kinases and the other by acetyl phosphate, was established by an analysis of wild-type DevS and phosphorylation-defective DevSH395Q mutant strains under conditions partially mimicking a granulomatous-like environment of acetate and hypoxia. Our findings reveal that DevR can be phosphorylated in vivo by acetyl phosphate. Importantly, we demonstrate that acetyl phosphate-dependent phosphorylation can occur in the absence of DevR's cognate kinases. Based on our findings, we conclude that anti-mycobacterial therapy should be targeted to DevR itself and not to DevS/DosT kinases.