Community perspective and healthcare assessment in malaria endemic states of India: a cross-sectional study protocol.

INTRODUCTION: India's contribution to the malaria burden was highest in South-East Asia Region in 2021, accounting for 79% of the estimated malaria cases and 83% of malaria-related deaths. Intensified Malaria Control Programme supported by Global Funds to Fight against AIDS, Tuberculosis and Malaria has deployed crucial interventions to reduce the overall burden of malaria in India. Evaluation of utilisation of malaria elimination interventions by the community and assessment of the healthcare system is underway in eleven high malaria endemic states in India. Health system preparedness for malaria elimination, logistics, and supply chain management of diagnostic kits and anti-malarial drugs in addition to the knowledge, attitude and practice of the healthcare workers is also being assessed. METHODS AND ANALYSIS: The study is being undertaken in 11 malaria endemic states with a variable annual parasite incidence of malaria. In total, 47 districts (administrative unit of malaria control operations) covering 37 976 households are to be interviewed and assessed. We present here the protocol following which the study is being undertaken at the behest and approval of Ministry of Health and Family Welfare in India. ETHICS AND DISSEMINATION: No patients were involved in the study. Study findings will be shared with Institutional ethics board of National Institute for Malaria Research New Delhi (NIMR) in a timely, comprehensive, accurate, unbiased, unambiguous and transparent manner and to the National Vector-borne Disease (Malaria) Control Programme officers and the Community public who participated. Important findings will be communicated through community outreach meetings which are existing in the Health system. Results will be informed to study participants via local fieldwork supervised by District Malaria Officers. Also findings will be published in reputed journals based on Indian Council of Medical Research (ICMR) publication policy.The ICMR-NIMR ethics committee approved the study via letter No. NIMR/ECM/2023/Feb/14 dated 24 April 2023 for version 5. All standard ethical practices will be followed.

Cardiac mitochondrial metabolism during pregnancy and the postpartum period.

The goal of the present study was to characterize changes in mitochondrial respiration in the maternal heart during pregnancy and after birth. Timed pregnancy studies were performed in 12-wk-old female FVB/NJ mice, and cardiac mitochondria were isolated from the following groups of mice: nonpregnant (NP), midpregnancy (MP), late pregnancy (LP), and 1-wk postbirth (PB). Similar to our previous studies, we observed increased heart size during all stages of pregnancy (e.g., MP and LP) and postbirth (e.g., PB) compared with NP mice. Differential cardiac gene and protein expression analyses revealed changes in several mitochondrial transcripts at LP and PB, including several mitochondrial complex subunits and members of the Slc family, important for mitochondrial substrate transport. Respirometry revealed that pyruvate- and glutamate-supported state 3 respiration was significantly higher in PB vs. LP mitochondria, with respiratory control ratio (RCR) values higher in PB mitochondria. In addition, we found that PB mitochondria respired more avidly when given 3-hydroxybutyrate (3-OHB) than mitochondria from NP, MP, and LP hearts, with no differences in RCR. These increases in respiration in PB hearts occurred independent of changes in mitochondrial yield but were associated with higher abundance of 3-hydroxybutyrate dehydrogenase 1. Collectively, these findings suggest that, after birth, maternal cardiac mitochondria have an increased capacity to use 3-OHB, pyruvate, and glutamate as energy sources; however, increases in mitochondrial efficiency in the postpartum heart appear limited to carbohydrate and amino acid metabolism.NEW & NOTEWORTHY Few studies have detailed the physiological adaptations that occur in the maternal heart. We and others have shown that pregnancy-induced cardiac growth is associated with significant changes in cardiac metabolism. Here, we examined mitochondrial respiration and substrate preference in isolated mitochondria from the maternal heart. We show that following birth, cardiac mitochondria are "primed" to respire on carbohydrate, amino acid, and ketone bodies. However, heightened respiratory efficiency is observed only with carbohydrate and amino acid sources. These results suggest that significant changes in mitochondrial respiration occur in the maternal heart in the postpartum period.

Malaria control - lessons learned from trends of Malaria indices over three decades in Karnataka, India.

BACKGROUND: Karnataka is one of the largest states in India and has a wide range of geographical terrains, ecotypes, and prevalence of malaria. It experiences a voluminous influx and efflux of people across the state that affects the spread of malaria. The state deployed focused intervention measures keeping the national objective of malaria elimination as the foremost priority. This brought down malaria cases below a thousand by the year 2021. Furthermore, the state is motivated toward malaria elimination by 2025. This study analyzes the trends in malaria indices over the past three decades in the state and highlights the key intervention measures that impacted the reduction in the malaria burden. METHODS: Data from 1991 to 2021 at the district level was collected from the archives of Regional Office for Health & Family Welfare (ROH&FW), Bangalore. Time-tend analysis on this data was conducted after categorization into three decades. Sequence plots were then plotted on the moving average of Annual Parasite Index for all those three decades. Generalized estimating equation model with Poisson distribution were used to evaluate difference in these indicators with pre and post interventions like LLIN, RDT with ACT and Guppy and Gambusia fishes. RESULTS: Malaria burden across the state has consistently declined over the last three decades with few years of exception. This has coincided with the mortality also steadily declining from 2006 and culminating in zero malaria deaths reported from 2011 to 2019. Morbidity had drastically reduced from the hundred-thousand (1993-2003) to ten thousand (2004-2016) thousands (2017-2020) of cases in this period and less than thousand cases were reported by 2021. Generalized estimating equation (GEE) model revealed significant difference of incidence risk ratio of malaria incidence and deaths, post introduction of interventions like LLIN, RDT with ACT and Guppy and Gambusia fishes, indicating these three as important interventions for reducing the malaria burden. Time trend analysis revealed a linear decreasing trend in malaria cases during 2011-2021 decade. CONCLUSIONS: A linear decreasing trend in malaria cases was observed during 2011-2021 decade. LLIN, RDT with ACT and Guppy and Gambusia fish's interventions significantly helped in reducing the state malaria burden.

Diagnostic Accuracy of Cartridge Based Nucleic Acid Amplification Test (CBNAAT) in Stool Samples in Pediatric Tuberculosis.

OBJECTIVES: To find out the diagnostic accuracy of stool Cartridge-based nucleic acid amplification test (CBNAAT) as an alternate method as compared to CBNAAT in gastric aspirate (GA) samples in pediatric tuberculosis (TB). METHODS: This cross-sectional study was performed at Department of Pediatrics of a tertiary care hospital. Children aged 0-18 y diagnosed as presumptive tuberculosis were consecutively enrolled. Gastric aspirate and corresponding stool sample was subjected to CBNAAT and its performance was compared in both samples using appropriate statistical tests. RESULTS: Total 100 patients were enrolled in the study. Diagnostic accuracy of CBNAAT was 81% and 80% in gastric aspirate and stool sample respectively. On comparing gastric aspirate with corresponding stool sample there was 97% agreement, with Cohen's kappa value of 0.94. There was a statistically significant association observed between gastric aspirate CBNAAT and stool CBNAAT p <0.001 using chi square test. Sensitivity of gastric aspirate CBNAAT and stool CBNAAT was 75% and 73% respectively and specificity was 100% for both the samples compared against Composite Reference Standard (CRS). CONCLUSIONS: The diagnostic accuracy of stool CBNAAT is comparable to GA CBNAAT in children and can be used as a good alternative to gastric aspirate for diagnosis of pulmonary and disseminated tuberculosis in children.

Comparative Evaluation of Abrasiveness among Three Dentifrices: An In Vitro Study.

Aim: A lot of herbal and medicated toothpastes having natural and antisensitivity properties are creating niches for themselves in the market. However, toothpaste containing high content of abrasives can be harmful to the teeth. The present in vitro study was conducted to assess the abrasiveness of three commercially available dentifrices on human-extracted anterior teeth on sound and demineralized enamel. Materials and methods: A total of 42 freshly extracted teeth were mounted on acrylic resin and randomly divided into three groups (group I, Colgate; II, Glister; and III, Dant Kanti). Each group consisted of one test tooth (partially) and one control tooth (completely) covered with nail varnish. The study had two phases. Phase 1-baseline average roughness (Ra) value was assessed with a profilometer of all the samples. Phase 2-further, teeth were immersed in the demineralizing solution for 4 days to allow the formation of an artificial carious lesion. Tooth brushing was performed by a customized automated toothbrushing model on all the teeth for 28 days. Ra value was again evaluated with Profilometer. Result: Data were analyzed, and a statistically significant result was observed with demineralized teeth in all three groups (p = 0.005). The intragroup comparison showed a significant difference with demineralized teeth of Colgate and Dant Kanti, (p =0.018) and (p =0.027), respectively. However, there was no significant difference in demineralized teeth of glister and sound teeth of all three groups. Conclusion: Glister was found to be the least abrasive of all three toothpastes, followed by Dant Kanti and Colgate. Clinical relevance: The particle size of the ingredients used in manufacturing toothpaste can lead to abrasion of the teeth.This, in combination with the hard bristles, can cause more harm to the teeth than good. The current study has compared the abrasive potential of three commercially available kinds of toothpaste. Hence daily use of these commercially available dental products should be used cautiously. How to cite this article: Priyam S, Sankeshwari R, Jalihal S, et al. Comparative Evaluation of Abrasiveness among Three Dentifrices: An In Vitro Study. Int J Clin Pediatr Dent 2023;16(2):264-269.

Ashwagandha (Withania somnifera) and Shunthi (Zingiber officinale) in mild and moderate COVID-19: An open-label randomized controlled exploratory trial.

BACKGROUND: Ayurveda interventions have been used for prophylaxis and care during the COVID-19 pandemic in India and have shown promising results in promoting early clinical recovery from COVID-19. OBJECTIVE: To assess the efficacy and safety of Ashwagandha [Withania somnifera (L.) Dunal] tablet and Shunthi (Zingiber officinale Roscoe) capsule in mild and moderate COVID-19 compared to conventional standard care. METHODS: A randomized controlled exploratory trial was conducted at a designated COVID-19 care center in India with 60 participants having mild or moderate COVID-19. Ashwagandha, two tablets (250 mg each), and Shunthi, two capsules (500 mg each) twice daily for 15 days, were given orally to the participants in the Ayurveda group (AG) and the control group (CG) received conventional standard care. The outcome measures included clinical recovery rate, the proportion of participants with negative RT-PCR assay for COVID-19 on day 7 and day 15, mean time to attain clinical recovery, change in pro-inflammatory markers, serum IgG for COVID-19, HRCT chest findings, disease progression and incidence of adverse events (AE). RESULTS: A total of 60 participants were enrolled, and the data of 48 participants (AG = 25 and CG = 23) were considered for the statistical analysis. The mean time for clinical recovery was reduced by almost 50 % in the AG (6.9 days) compared to CG (13.0 days) (p < 0.001). The proportion of participants who attained viral clearance in AG was 76.0 % compared to 60.8 % in the CG (RR= 1.24, 95 % CI: 0.841, 1.851, p-value = 0.270). Changes in the pro-inflammatory markers, serum IgG for COVID-19, and HRCT chest findings were comparable in both groups, and no AE or disease progression was reported. CONCLUSIONS: The Ayurveda interventions, Ashwagandha and Shunthi, can effectively reduce the duration of clinical recovery and improve time for viral clearance in mild and moderate COVID-19. These interventions were observed to be safe and well-tolerated during the duration of the trial. TRIAL REGISTRATION: Clinical Trial Registry of India - CTRI/2020/08/027224.

Bone Marrow and Wharton's Jelly Mesenchymal Stromal Cells are Ineffective for Myocardial Repair in an Immunodeficient Rat Model of Chronic Ischemic Cardiomyopathy.

BACKGROUND: Although cell therapy provides benefits for outcomes of heart failure, the most optimal cell type to be used clinically remains unknown. Most of the cell products used for therapy in humans require in vitro expansion to obtain a suitable number of cells for treatment; however, the clinical background of the donor and limited starting material may result in the impaired proliferative and reparative capacity of the cells expanded in vitro. Wharton's jelly mesenchymal cells (WJ MSCs) provide a multitude of advantages over adult tissue-derived cell products for therapy. These include large starting tissue material, superior proliferative capacity, and disease-free donors. Thus, WJ MSC if effective would be the most optimal cell source for clinical use. OBJECTIVES: This study evaluated the therapeutic efficacy of Wharton's jelly (WJ) and bone marrow (BM) mesenchymal stromal cells (MSCs) in chronic ischemic cardiomyopathy in rats. METHODS: Human WJ MSCs and BM MSCs were expanded in vitro, characterized, and evaluated for therapeutic efficacy in a immunodeficient rat model of ischemic cardiomyopathy. Cardiac function was evaluated with hemodynamics and echocardiography. The extent of cardiac fibrosis, hypertrophy, and inflammation was assessed with histological analysis. RESULTS: In vitro analysis revealed that WJ MSCs and BM MSCs are morphologically and immunophenotypically indistinguishable. Nevertheless, the functional analysis showed that WJ MSCs have a superior proliferative capacity, less senescent phenotype, and distinct transcriptomic profile compared to BM MSC. WJ MSCs and BM MSC injected in rat hearts chronically after MI produced a small, but not significant improvement in heart structure and function. Histological analysis showed no difference in the scar size, collagen content, cardiomyocyte cross-sectional area, and immune cell count. CONCLUSIONS: Human WJ and BM MSC have a small but not significant effect on cardiac structure and function when injected intramyocardially in immunodeficient rats chronically after MI.

Effect on neonatal sepsis following immediate kangaroo mother care in a newborn intensive care unit: a post-hoc analysis of a multicentre, open-label, randomised controlled trial.

Background: To implement the immediate Kangaroo mother care (iKMC) intervention in the previous multicentre, open-label, randomised controlled trial, the mother or a surrogate caregiver and neonate needed to be together continuously, which led to the concept of the Mother-Newborn Care Unit (MNCU). Health-care providers and administrators were concerned of the potential increase in infections caused by the continuous presence of mothers or surrogates in the MNCU. We aimed to assess the incidence of neonatal sepsis in sub-groups and the bacterial profile among intervention and control neonates in the study population. Methods: This is a post-hoc analysis of the previous iKMC trial, which was conducted in five level 2 Newborn Intensive Care Units (NICUs) one each in Ghana, India, Malawi, Nigeria, and Tanzania, in neonates with birth weight 1 to <1.8 kg. The intervention was KMC initiated immediately after birth and continued until discharge and compared to conventional care with KMC initiated after meeting stability criteria. The primary outcomes of this report were the incidence of neonatal sepsis in sub-groups, sepsis-related mortality and bacterial profile of isolates during hospital stay. The original trial is registered with the Australia and New Zealand Clinical Trials Registry (ACTRN12618001880235) and the Clinical Trials Registry-India (CTRI/2018/08/01536). Findings: Between November 30, 2017, and January 20, 2020, 1609 newborns in the intervention group and in the control group 1602 newborns were enrolled in iKMC study. 1575 newborns in the intervention group and 1561 in the control group were clinically evaluated for sepsis. Suspected sepsis was 14% lower in intervention group in sub-group of neonates with birth weight 1.0-<1.5 kg; RR 0.86 (CI 0.75, 0.99). Among neonates with birth weight 1.5-<1.8 kg, suspected sepsis was reduced by 24%; RR 0.76 (CI 0.62, 0.93). Suspected sepsis rates were lower in intervention group than in the control group across all sites. Sepsis related mortality was 37% less in intervention group than the control group; RR 0.63 (CI 0.47-0.85) which was statistically significant. The intervention group had fewer cases of Gram-negative isolates (n = 9) than Gram positive isolates (n = 16). The control group had more cases of Gram-negative isolates (n = 18) than Gram positive (n = 12). Interpretation: Immediate Kangaroo Mother care is an effective intervention to prevent neonatal sepsis and sepsis related mortality. Funding: The original trial was funded by the Bill and Melinda Gates Foundation through a grant to the World Health Organization (grant No. OPP1151718).

Mutant and curli-producing E. coli enhance the disease phenotype in a hSOD1-G93A mouse model of ALS.

The gut microbiome is a potential non-genetic contributing factor for Amyotrophic Lateral Sclerosis. Differences in gut microbial communities have been detected between ALS subjects and healthy controls, including an increase in Escherichia coli in ALS subjects. E. coli and other gram-negative bacteria produce curli proteins, which are functional bacterial amyloids. We examined whether long-term curli overexposure in the gut can exacerbate the development and progression of ALS. We utilized the slow-developing hSOD1-G93A mouse model of ALS with their C57BL/6J WT littermate controls, including males and females, with a total of 91 animals. These mice were on a normal chow diet and fed curli-producing or curli-nonproducing (mutant) E. coli in applesauce (vehicle) 3 times/week, from 1 through 7 months of age. Male hSOD1 mice demonstrated gradual slowing in running speed month 4 onwards, while females exhibited no signs of locomotive impairment even at 7 months of age. Around the same time, male hSOD1 mice showed a gradual increase in frequency of peripheral CD19+ B cells. Among the male hSOD1 group, chronic gut exposure to curli-producing E. coli led to significant shifts in α- and ß-diversities. Curli-exposed males showed suppression of immune responses in circulation, but an increase in markers of inflammation, autophagy and protein turnover in skeletal muscle. Some of these markers were also changed in mutant E. coli-exposed mice, including astrogliosis in the brainstem and demyelination in the lumbar spinal cord. Overall, chronic overexposure to a commensal bacteria like E. coli led to distant organ pathology in our model, without the presence of a leaky gut at 6 months. Mechanisms underlying gut-distant organ communication are of tremendous interest to all disciplines.

Effects of glenohumeral corticosteroid injection on stiffness following arthroscopic rotator cuff repair: a prospective, multicentric, case-control study with 18-month follow-up.

BACKGROUND: This study aimed to analyze the efficacy of single-dose corticosteroid injection (CSI) administered at 6 weeks postoperative to treat stiffness following arthroscopic rotator cuff repair (ARCR). METHODS: In this prospective, multicentric, case-control study, post-ARCR stiffness at 6 weeks was treated with either a single dose of intra-articular CSI (CSI group) or physical therapy with oral analgesics (non-CSI group). Pain intensity according to visual analog scale (VAS), functional outcome using the Constant Murley Shoulder Score, time to return to activities of daily living (ADLs), and retear rate were recorded at 6 weeks, 9 weeks, 12 weeks, 6 months, 12 months, and 18 months postoperatively in both groups. RESULTS: A total of 149 patients (54.5%) in the CSI group and 124 patients (45.5%) in the non-CSI group were included in this study. Pain and function were significantly better in the CSI group at 9-week, 12-week, and 6-month (P<0.001) follow-up, whereas they were not significantly different when the groups were compared at 12- and 18-month follow-up. The mean duration to return to ADLs was significantly shorter (P<0.001) in the CSI group. The incidence of retears was not significantly different (P=0.36) between groups at the end of 18 months of follow-up. CONCLUSIONS: Single-dose intra-articular CSI administered at 6 weeks postoperative to treat post-ARCR stiffness significantly improved pain, function, and duration of return to ADLs without increasing the risk of retears compared to patients who did not receive intra-articular CSI.

Functional and clinical outcome of anterior cruciate ligament reconstruction with peroneus longus autograft and correlation with MRI after 3 years.

Introduction: Autograft options for anterior cruciate ligament reconstruction over the years have gone from bone-patellar tendon-bone to hamstring to peroneus longus tendon. Considering the drawbacks of other autografts, we analyse peroneus longus autograft holistically as a viable alternative. Materials and methods: This was a prospective study of 113 patients undergoing anterior cruciate ligament reconstruction with peroneus longus autograft between January 2017 and November 2018 for isolated, full-thickness ACL tears. Functional analysis was done using the Tegner-Lysholm score pre-operatively, at 6 months, 1 year, 2 years, and 3 years postoperatively. At terminal follow-up, stability was checked clinically by Lachman test, residual morbidity of donor site was assessed using foot and ankle disability index, and radiographic correlation was done with magnetic resonance imaging. Results: The mean diameter of the graft after tripling was 9 ± 0.71 mm and the average length before tripling was found to be 27.07 ± 2.76 cms. At terminal follow-up, 101 patients showed excellent, while 12 patients showed good outcomes. The mean foot and ankle disability index was 94.8 ± 3. 90.27% of patients had no laxity on clinical examination, and magnetic resonance imaging of all the patients at terminal follow-up showed good graft uptake. Conclusions: Peroneus longus autograft shows intraoperative consistency and gives excellent functional outcome, clinical stability, and no donor site morbidity even three years postoperatively.

Dynamic Electrolyte Spreading during Meniscus-Confined Electrodeposition and Electrodissolution of Copper for Surface Patterning.

Meniscus-confined electrodeposition and electrodissolution are a facile maskless approach to generate controlled surface patterns and 3D microstructures. In these processes, the solid-liquid interfacial area confined by the meniscus dictates the zone on which the electrodeposition or the electrodissolution occurs. In this work, we show that the process of electrodeposition or electrodissolution in a meniscus-confined droplet system can lead to dynamic spreading of the meniscus, thereby changing the solid-liquid interfacial area confined by the meniscus. Our results show that the wetting dynamics depends on the applied voltage and the type of interface underneath the droplet, specifically a smooth surface with a homogeneous solid-liquid interface or a superhydrophobic surface with a heterogeneous solid-liquid and liquid-vapor interface. It is found that both electrodissolution and electrodeposition processes induced droplet spreading in the case of a smooth surface with a homogeneous interface. However, a superhydrophobic surface with a heterogeneous interface under the droplet produced nonlinear spreading during electrodissolution and spreading inhibition during electrodeposition. The underlying mechanisms resulting in the observed behavior have been explicated. The dynamic droplet spreading could modify the dimensions of the patterns formed and hence is of immense importance to the meniscus-confined electrochemical micromachining. The findings also provide fundamental insights into the spreading behavior and wetting transitions induced by electrochemical reactions.

Disease Characteristics, Care-Seeking Behavior, and Outcomes Associated With the Use of AYUSH-64 in COVID-19 Patients in Home Isolation in India: A Community-Based Cross-Sectional Analysis.

Background: During the second wave of the COVID-19 pandemic in India, the Ministry of Ayush conducted a community study to provide therapeutic care to patients with asymptomatic, mild, and moderate COVID-19 in home isolation based on the empirical evidence generated on the efficacy of AYUSH-64 in COVID-19. Objective: To document disease characteristics, care-seeking behavior, and outcomes in patients with asymptomatic, mild, or moderate COVID-19 in home isolation who used AYUSH-64 for COVID-19. Methods: Cross-sectional analysis of the data generated through a community study conducted in India from 08 May to 31 August 2021 was performed to study the disease characteristics, care-seeking behavior during home isolation, clinical outcomes, adverse events, and the association between various risk factors and clinical recovery during the study period. The data were collected through semi-structured questionnaires, available in electronic data collection format at the baseline, 7, 14, and 21 days. A logistic regression was performed to explore the relationship between relevant variables and clinical recovery. Results: Data from 64,642 participants were analyzed for baseline assessment, and final analysis was done for 49,770 participants. The mean age of the enrolled participants was 38.8 ± 11.7 years, and 8.4% had co-morbidities. AYUSH-64 was utilized as an add-on to the standard care by 58.3% of participants. Comparable clinical outcomes were observed in participants utilizing AYUSH-64 either as a standalone or as an add-on to standard care, in terms of clinical recovery, disease progression, the requirement for oxygen supplementation, hospitalization, ICU admission, and need for ventilator support. Younger age, having no co-morbidities or substance abuse, and having been vaccinated were associated with early clinical recovery than those who were older and not vaccinated. Conclusions: The study findings suggest that AYUSH-64 use, either standalone or as an adjunct to standard care, in asymptomatic, mild, or moderate COVID-19 is associated with good clinical outcomes. Ayush services and interventions can be effectively integrated into the mainstream public health architecture to serve public health goals.

AYUSH-64 as an adjunct to standard care in mild to moderate COVID-19: An open-label randomized controlled trial in Chandigarh, India.

OBJECTIVE: To determine the therapeutic efficacy and safety of AYUSH-64 as an add-on to standard care in mild to moderate COVID-19. DESIGN SETTING, AND INTERVENTIONS: This open-label randomized controlled parallel-group trial was conducted at a designated COVID care centre in India in 80 patients diagnosed with mild to moderate COVID-19 and randomized into two groups. Participants in the AYUSH-64 add-on group (AG) received AYUSH-64 two tablets (500 mg each) three times a day for 30 days along with standard conventional care. The control group (CG) received standard care alone. MAIN OUTCOME MEASURES: Proportion of participants who attained clinical recovery on day 7, 15, 23 and 30, proportion of participants with negative RT-PCR assay for COVID-19 at each weekly time point, change in pro-inflammatory markers, metabolic functions, HRCT chest (CO-RADS category) and incidence of Adverse Drug Reaction (ADR)/Adverse Event (AE). RESULTS: Out of 80 participants, 74 (37 in each group) contributed to the final analysis. Significant difference was observed in clinical recovery in the AG (p < 0.001 ) compared to CG. Mean duration for clinical recovery in AG (5.8 ± 2.67 days) was significantly less compared to CG (10.0 ± 4.06 days). Significant improvement in HRCT chest was observed in AG (p = 0.031) unlike in CG (p = 0.210). No ADR/SAE was observed or reported in AG. CONCLUSIONS: AYUSH-64 as adjunct to standard care is safe and effective in hastening clinical recovery in mild to moderate COVID-19. The efficacy may be further validated by larger multi-center double-blind trials.

Age-Associated Gut Dysbiosis, Marked by Loss of Butyrogenic Potential, Correlates With Altered Plasma Tryptophan Metabolites in Older People Living With HIV.

BACKGROUND: Imbalance in tryptophan (TRP) metabolism and its neuroactive metabolites, serotonin and kynurenine (KYN), is a known pathogenic mechanism underlying neurocognitive impairment. Gut microbiota plays an important role in TRP metabolism, and the production of these neuroactive molecules affects neurocognitive function. Although both HIV infection and normal aging independently induce gut dysbiosis and influence TRP metabolism, their interactive effects on compositional/functional changes in gut microbiota and consequent alterations in TRP metabolites remain largely undetermined. METHODS: Older people living with HIV infection (PLWH, aged 50-70 years, n = 22) were enrolled in this cross-sectional pilot study. Metagenomic analysis of fecal microbiome using 16S Ribosomal ribonucleic acid gene sequencing and metabolomics analysis of plasma using mass spectrometry with a reverse-phase iquid chromatography tandem mass spectrometry were performed. Statistical analyses included the univariate linear regression and Spearman correlation analyses. RESULTS: Age-associated changes in plasma levels of key neuroactive TRP metabolites, serotonin and KYN, were seen in PLWH. Specifically, we observed age-dependent decreases in serotonin and increases in KYN and KYN-to-TRP ratio, indicative of dysfunctional TRP metabolism. Furthermore, the gut dysbiosis seen in older PLWH is characterized by a reduction of Firmicutes/Bacteroidetes ratio and butyrate-producing microbial families Lachnospiraceae and Lactobacillaceae. Of importance, correspondent with gut dysbiosis, increasing age was significantly associated with decreased plasma butyrate levels, which in turn correlated positively with serotonin and negatively with KYN/TRP ratio. CONCLUSIONS: Age-dependent gut microbial dysbiosis distinguished by a decrease in butyrogenic potential is a key pathogenic feature associated with the shift in TRP metabolism from serotonin to KYN in older PLWH.

AYUSH 64, a polyherbal Ayurvedic formulation in Influenza-like illness - Results of a pilot study.

BACKGROUND: Influenza-like Illness (ILI) refers to a wide range of viral infections with an important cause of morbidity and mortality worldwide. The global incidence of ILI is estimated at 5-10% in adults and 20-30% in children. In India influenza accounts for 20-42% of monthly acute medical illness hospitalizations during the peak rainy season. AYUSH-64, a poly-herbal drug, is in practice for 40 years for various clinical conditions like fevers, microfilaremia, and inflammatory conditions. OBJECTIVE: A pilot study was conducted to evaluate the safety and efficacy of Ayurvedic formulation, AYUSH-64 in clinically diagnosed ILI for accelerating the recovery. MATERIAL AND METHODS: A prospective, open-label, nonrandomized, single group, single-center pilot clinical study with pre-test and post-test design was conducted at Raja Ramdeo Anandilal Podar Central Ayurveda Research Institute for Cancer, Mumbai, an institute of Central Council for Research in Ayurvedic Sciences (CCRAS) between June 2018 and July 2019. A total of 38 participants of clinically diagnosed ILI (18-65 years) were studied with an one-week intervention of 'AYUSH 64' in a dose of 3 gm/day and three weeks post-treatment observation period. Assessment of parameters viz. improvement in the symptoms of ILI, frequency of usage of acetaminophen, antihistaminic and cough syrup, hematology, liver function and kidney function tests along with incidence of secondary complications, and time to return to a normal routine was done. RESULTS: One-week intervention of AYUSH 64 helped to recover from ILI symptoms with reduced frequency of usage of acetaminophen and antihistaminic. The intervention was safe on hematology and biochemical parameters. No serious adverse effects were observed during the study. CONCLUSION: AYUSH 64 along-with standard care in ILI is safe and efficacious and this may be used in other viral infections with pyrexia as add-on to standard care for early recovery and better outcome.

A pilot clinical study of an add-on Ayurvedic formulation containing Tinospora cordifolia and Piper longum in mild to moderate COVID-19.

BACKGROUND: After declaration of COVID- 19 as pandemic by WHO, countries adopted several measures to contain the spread as well as test and treat the patients. Further, as no effective management protocols to address this pandemic were available, a need was felt to explore the integration of modern and traditional medicines to treat COVID- 19 cases. OBJECTIVE: To undertake a study with Ayurveda formulation as add on to existing standard of care (SOC) and to compare the outcomes in terms of patient acceptability, the time to clinical recovery, hospital stay as well as any signs of drug-herb interaction between the Ayurveda formulation and the SOC. MATERIAL AND METHODS: An exploratory nonrandomized prospective study has been undertaken for comparing the outcomes of traditional Ayurvedic classical formulation of Tinospora cordifolia (Guduchi) and Piper longum (Pippali) as an add on to standard of care (SOC) using modern medicine with SOC alone. This has been done in mild and moderate COVID- 19 cases, at a tertiary care integrative Medicine hospital in the National Capital Region, Gurgaon, India. The outcomes have been evaluated in terms of the duration of hospital stay, the time to clinical recovery, safety and non- interference/interaction of Ayurvedic and Further, long term impact of COVID- 19 treatment has been evaluated using quality of life questionnaire after 3 months of discharge. RESULTS: Findings of present study reveals that the Ayurveda add-on formulation of T. cordifolia (Guduchi) and P. longum (Pippali) has reduced the length of hospital stay and improve the recovery time. General feeling of wellbeing and activity levels were better in the 3 month follow-up post discharge in the Ayurveda add-on group. CONCLUSION: Addition of Ayurveda formulation has reduced the time of recovery and duration of hospital stay. However, this formulation needs further investigated to provide more information on effective and safe herbal add-on to SOC for better outcomes to treatment of COVID-19 disease.