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Aim: The main aim of the study is to compare the efficacy of add-on therapy of teneligliptin (20 once daily) versus pioglitazone (15 mg once daily) among type 2 diabetes mellitus (T2DM) patients inadequately controlled on dual therapy of metformin (MF) plus sulfonylurea (SU). Materials and Methods: It is a prospective, observational, comparative study conducted in patients from the outpatient department of Sri Bhadrakali Hospital located at Warangal, Telangana state, India. The efficacy of pioglitazone and teneligliptin was assessed by measuring the change in the glycated haemoglobin (HbA1c), Fasting Plasma Glucose (FPG), Post Prandial Blood Glucose (PPBH) levels after 12 weeks of treatment. FPG, PPBG and HbA1c levels at baseline and 12 weeks. The primary endpoint was changed in HbA1c levels at 12 weeks as compared to the baseline levels in both groups. The secondary endpoints were changes in FPG, PPBG levels at 12 weeks as compared to baseline levels. Along with, serum cholesterol, triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels were measured both at baseline and after 12 weeks. Results: At study end, HbA1c levels were reduced from baseline by 0.7% (P = 0.0049) in the pioglitazone group and 1% (P = 0.0002) in the teneligliptin group. The mean changes in FPG levels from baseline to week 12 were −39.8 mg/dl (P ≤ 0.0001) in teneligliptin and −11.48 mg/dl (P = 0.00380) in pioglitazone group. The mean PPG levels from −47.8 mg/dl (P = 0.0003) in teneligliptin and −25.5 mg/dl (P = 0015) in pioglitazone group. After 12 weeks of study, the levels of TG, total cholesterol (TC), LDL −71.5 (P = 0.0973), −15 (P = 0.0501), 18.8 (P ≤ 0.0008) mg/dl and −31.38 (P ≤ 0.0001), −21 (P ≤ 0.0001), −11.68 (P = 0.0028) mg/dl in teneligliptin group and pioglitazone group, respectively. There was significant increase in HDL levels 5.3 (P ≤ 0.0001) mg/dl in teneligliptin group and 5.2 (P = 0.0001) mg/dl in pioglitazone group. Conclusion: Both teneligliptin 20 mg and Pioglitazone 15 mg provided additional HbA1c lowering to that achieved with MF and SU. Teneligliptin showed more effective reductions in HbA1c, FPG, PPBG, HDL and LDL levels. Pioglitazone showed significant changes in HbA1c, HDL, TC, triglyceride levels and significant changes in FPG, PPBG and LDL levels. Reduction in HbA1c and plasma lipids slows down the diabetes progression and decreases the risk of microvascular and macrovascular complications.

Irbesartan (IR) is an angiotensin II receptor antagonist drug with antihypertensive activity. IR bioavailability is limited due to poor solubility and first-pass metabolism. The current investigation aimed to design, develop, and characterize the cyclodextrin(s) (CD) complexed IR (IR-CD) loaded solid lipid nanoparticles (IR-CD-SLNs) for enhanced solubility, sustained release behavior, and subsequently improved bioavailability through oral administration. Based on phase solubility studies, solid complexes were prepared by the coacervation followed by lyophilization method and characterized for drug content, inclusion efficiency, solubility, and in vitro dissolution. IR-CD inclusion complexes demonstrated enhancement of solubility and dissolution rate of IR. However, the dissolution efficiency was significantly increased with hydroxypropyl-βCD (HP-βCD) inclusion complex than beta-CD (βCD). SLNs were obtained by hot homogenization coupled with the ultrasonication method with IR/HP-βCD inclusion complex loaded into Dynasan 112 and glycerol monostearate (GMS). SLNs were evaluated for physicochemical characteristics, in vitro release, differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), and physical stability at room temperature for two months. The optimized SLNs formulation showed particle size, polydispersity index, zeta potential, assay, and entrapment efficiency of 257.6 ± 5.1 nm, 0.21 ± 0.03, −30.5 ± 4.1 mV, 99.8 ± 2.5, and 93.7 ± 2.5%, respectively. IR-CD-SLN and IR-SLN dispersions showed sustained release of IR compared to the IR-CD inclusion complexes. DSC results complimented PXRD results by the absence of IR endothermic peak. Optimized IR-CD complex, IR-SLN, and IR-CD-SLN formulations were stable for two months at room temperature. Thus, the current IR oral formulation may exhibit improved oral bioavailability and prolonged antihypertensive activity, which may improve therapeutic outcomes in the treatment of hypertension and heart failure.

Objectives. To measure and compare free fraction of serum levels of VPA (valproic acid) between non-malnourished and malnourished epileptic children and to evaluate the adverse effects (myopathy, hepatotoxicity). Material and methods. It is a prospective comparative observational case control study in which forty epileptic children (malnourished: 18 male/8 female, age 8.3±2.5, non-malnourished: 8 male/6 female, age 8.1±2.1) who fulfilled the inclusion criteria were recruited as study group and twenty children as control group (12male/8 female, age 6.0±2.8). Outcome measures monitored are serum VPA levels (total and free fraction of serum VPA), serum CK (creatinine kinase), SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase). Using screening tool for the assessment of malnutrition in pediatrics (STAMP©), subjects are categorized into mild, moderate, severe malnourished as -1SD, -2SD, -3SD respectively. Outcomes. There is an elevation in mean free fraction of VPA is 17.3±6.4 μg/ml whereas in non-malnourished group it was found to be 8.7±4.2 μg/ml with P=

Abstract In the years 2021–2022 and 2022–2023, an experiment was carried out at the IFS Unit, College of Agriculture, PJTSAU, Rajendranagar in order to determine the best one-acre integrated farming system model for Telangana's small and marginal farmers. Seven farm models among which six models were developed by combining the various components i.e., cropping systems, fruit cropfodder crops and livestock components, in different proportions, and compared with rice-groundnut system which is a major farming approach in Telangana using randomized block design. The seven models were as follows: M1: Rice–Groundnut; M2: Rice–Groundnut, Pigeonpea + Sweetcorn (1:3)—Bajra, Bt cotton + Greengram (1:2)—Maize; M3: Rice–Groundnut, Pigeonpea + Sweetcorn (1:3)—Bajra, Pigeonpea + Maize (1:3)—Sunhemp; Napier grass, Sheep (5 + 1); M4: Rice–Groundnut, Pigeonpea + Sweetcorn (1:3)—Bajra, Bt cotton + Greengram (1:2)—Maize, Pigeonpea + Maize (1:3)—Sunhemp, Poultry unit; M5: Guava, Hedge Lucerne, Napier grass, Bt cotton + Greengram (1:2)—Maize, Sheep (5 + 1); M6: Guava, Bt cotton + Greengram (1:2)—Maize, Rice–Groundnut, Poultry; M7: Rice–Groundnut, Pigeonpea + Sweetcorn (1:3)—Bajra, Pigeonpea + Maize (1:3)—Sunhemp; Napier grass, Hedge lucerne, Poultry (100), Sheep (5 + 1). Based on a 2-year average, the Model M7 system produced 9980 Rice Grain Equivalent Yield(RGEY)kg of output per acre, with gross and net returns of ₹210,439 and ₹124,953 respectively, and recovered a B:C ratio of 2.46. It has recorded highest sustainable yield index (SYI) of 0.673 and value index of 0.772 with the lowest water footprint of 259.0 L/kg. This study reveals that adopting an integrated farming system is the optimal approach for effectively combining productive, financially rewarding, and diversified enterprises within a single acre of land.d. This system should be recommended for maximum benefits to smallto small and marginal farmers in Telangana's southern hills and plateau.

Agar well diffusion method was used to evaluate the antimicrobial potential of Justicia neesii extract. The maximum activity index (AI) values are observed against Klebsiella pneumonia (1.208) and low AI value for Streptococcus faecalis (0.963) compared to other bacterial species. The maximum AI values are observed against Saccharomyces cerevisiae (1.147) and low AI value for Fusarium axisporum (0.986) compared to other fungal species. The MIC and MBC/MFC values indicated the bacteriostatic/ fungistatic nature of the extract and also having good correlation with the zone of inhibition values. The total activity values indicated that J. neesii extract can show antimicrobial activity even at higher dilutions, except for Gram negative bacteria.

Background: Various forms of commonly used noninvasive respiratory support strategies have considerable effect on diaphragmatic contractile function which can be evaluated using sonographic diaphragm activity parameters. Objective: To compare the magnitude of respiratory workload decreased as assessed by thickening fraction of the diaphragm and longitudinal diaphragmatic strain while using high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) modes [nasal intermittent positive pressure ventilation (NIPPV) and bilevel positive airway pressure (BiPAP)] in pediatric patients after cardiothoracic surgery. Methodology: This prospective randomized controlled trial was performed at a tertiary care surgical intensive care unit in postcardiac surgery patients aged between 1 and 48 months, who were randomly allocated into three groups: 1) HFNC (with flows at 2 L/kg/min), 2) NIPPV via RAMS cannula in PSV mode (pressure support 8 cmH2O, PEEP 5 cmH2O), and 3) BiPAP in nCPAP mode (CPAP of 5 cmH2O). Measurements were recorded at baseline after extubation (R0) and subsequently every 12 hourly (R1, R2, R3, R4, R5) at 12, 24, 36, 48, and 60 hours respectively until therapy was discontinued. Results: Sixty patients were included, with 20 patients each in the NIPPV group, HFNC group, and BiPAP group. Longitudinal strain at crura of diaphragm was lower in the BiPAP group as compared to HFNC group at R2-R4 [R2 (-4.27± -2.73 vs - 8.40± -6.40, P = 0.031), R3 (-5.32± -2.28 vs -8.44± -5.6, P = 0.015), and R4 (-3.8± -3.42 vs -12.4± -7.12, P = 0.040)]. PFR was higher in HFNC than NIPPV group at baseline and R1-R3[R0 (323 ± 114 vs 264 ± 80, P = 0.008), R1 (311 ± 114 vs 233 ± 66, P = 0.022), R2 (328 ± 116 vs 237 ± 4, P = 0.002), R3 (346 ± 112 vs 238 ± 54, P = 0.001)]. DTF and clinical parameters of increased work of breathing remain comparable between three groups. The rate of reintubation (within 48 hours of extubation or at ICU discharge) was 0.06% (1 in NIPPV, 1 in BiPAP, 2 in HFNC) and remain comparable between groups (P = 1.0). Conclusion: BiPAP may provide better decrease in work of breathing compared to HFNC as reflected by lower crural diaphragmatic strain pattern. HFNC may provide better oxygenation compared to NIPPV group, as reflected by higher PFR ratio. Failure rate and safety profile are similar among different methods used.

Background: Mycobacterium w (Mw), an immunomodulator, resulted in better clinical status in severe coronavirus infectious disease 19 (COVID-19) but no survival benefit in a previous study. Herein, we investigate whether Mw could improve clinical outcomes and survival in COVID-19. Materials and Methods: In a multicentric, randomized, double-blind, parallel-group, placebo-controlled trial, we randomized hospitalized subjects with severe COVID-19 to receive either 0.3 mL/day of Mw intradermally or a matching placebo for three consecutive days. The primary outcome was 28-day mortality. The co-primary outcome was the distribution of clinical status assessed on a seven-point ordinal scale ranging from discharged (category 1) to death (category 7) on study days 14, 21, and 28. The key secondary outcomes were the change in sequential organ failure assessment (SOFA) score on days 7 and 14 compared to the baseline, treatment-emergent adverse events, and others. Results: We included 273 subjects (136 Mw, 137 placebo). The use of Mw did not improve 28-day survival (Mw vs. placebo, 18 [13.2%] vs. 12 [8.8%], P = 0.259) or the clinical status on days 14 (odds ratio [OR], 1.33; 95% confidence intervals [CI], 0.79-2.3), 21 (OR, 1.49; 95% CI, 0.83-2.7) or 28 (OR, 1.49; 95% CI, 0.79-2.8) between the two study arms. There was no difference in the delta SOFA score or other secondary outcomes between the two groups. We observed higher injection site reactions with Mw. Conclusion: Mw did not reduce 28-day mortality or improve clinical status on days 14, 21 and 28 compared to placebo in patients with severe COVID-19. [Trial identifier: CTRI/2020/04/024846]

Abstract Objective: We aimed to assess risk of COVID-19 infection & seroprotection status in healthcare workers (HCWs) in both hospital and community settings following an intensive vaccination drive in India. Setting: Tertiary Care Hospital Methods: We surveyed COVID-19 exposure risk, personal protective equipment (PPE) compliance, vaccination status, mental health & COVID-19 infection rate across different HCW cadres. Elecsys® test for COVID-19 spike (Anti-SARS-CoV-2S; ACOVs) and nucleocapsid (Anti-SARS-CoV-2; ACOV) responses following vaccination and/or COVID-19 infection were measured in a stratified sample of 386 HCW. Results: We enrolled 945 HCWs (60.6% male, age 35.9 ± 9.8 years, 352 nurses, 211 doctors, 248 paramedics & 134 support staff). Hospital PPE compliance was 90.8%. Vaccination coverage was 891/945 (94.3%). ACOVs neutralizing antibody was reactive in 381/386 (98.7%). ACOVs titer (U/ml) was higher in the post-COVID-19 infection group (N =269; 242.1 ± 35.7 U/ml) than in the post-vaccine or never infected subgroup (N = 115, 204.1 ± 81.3 U/ml). RT PCR + COVID-19 infections were documented in 224/945 (23.7%) and 6 HCWs had disease of moderate severity, with no deaths. However, 232/386 (60.1%) of HCWs tested positive for nucleocapsid ACOV antibody, suggesting undocumented or subclinical COVID-19 infection. On multivariate logistic regression, only female gender [aOR 1.79, 95% CI 1.07–3.0, P = .025] and COVID-19 family contact [aOR 5.1, 95% CI 3.84–9.5, P < .001] were predictors of risk of developing COVID-19 infection, independent of association with patient-related exposure. Conclusion: Our HCWs were PPE compliant and vaccine motivated, with immunization coverage of 94.3% and seroprotection rate of 98.7%. There was no relationship between HCW COVID-19 infection to exposure characteristics in the hospital. Vaccination reduced disease severity and prevented death in HCW.

The novel coronavirus disease (COVID-19) was caused by a new strain of the virus SARS-CoV-2 in December 2019 emerged as deadly pandemic that affected millions of people worldwide. Factors such as lack of effective drugs, vaccine resistance, gene mutations, and cost of repurposed drugs demand new potential inhibitors. The main protease (Mpro) of SARS-CoV-2 has a key role in viral replication and transcription and is considered as drug target for new lead identification. In this present work, structure-based virtual screening, docking, MM/GBSA, AutoDock, ADME, and MD simulations-based optimization was proposed for the identification of new potential inhibitors against Mpro of SARS-CoV-2. The ligand molecules M1, M3, and M6 were identified as potential leads from lead optimization. Induced fit docking was performed for the identification of the best poses of lead molecules. The best docked poses of potential leads M1 and M3 were subject to 100 ns MD simulations for the evaluation of stability and interaction analysis into Mpro active site. The structures of the top two leads M1 and M3 were optimized based on MD simulation conformational changes and isoster scanning, designed as new leads M7 and M8. The MD simulation trajectories RMSD, RMSF, protein-ligand, ligand-protein interaction plots, and ligand torsion profiles were analyzed for stability interpretation. The docked complexes of M7 and M8 of Mpro exhibited equilibrated and converged plots in 100 ns simulation. The lead molecules M1, M3, M7, and M8 were identified as potential SARS-CoV-2 inhibitors for COVID-19 disease. A comparative docking study was carried out using FDA-approved drugs to support the potential binding affinities of newly identified lead inhibitors.

In this study, a novel series of histone deacetylases 6 (HDAC6) inhibitors containing polycyclic aromatic rings were discovered and evaluated for their pharmacological activities. The most potent compound 10c exhibited high HDAC6 inhibitory activity (IC50 = 261 nM) and excellent HDAC6 selectivity (SI = 109 for HDAC6 over HDAC3). 10c also showed decent antiproliferative activity in vitro with IC50 of 7.37–21.84 μM against four cancer cell lines, comparable to that of tubastatin A (average IC50 = 6.10 μM). Further mechanism studies revealed that 10c efficiently induced apoptosis and S-phase arrest in B16-F10 cells. In addition, 10c markedly increased the expression of acetylated-α-tubulin both in vitro and in vivo, without affecting the levels of acetylated-H3 (marker of HDAC1 inhibition). Furthermore, 10c (80 mg/kg) exhibited moderate antitumor efficacy in a melanoma tumour model with a tumour growth inhibition (TGI) of 32.9%, comparable to that (TGI = 31.3%) of tubastatin A. Importantly, the combination of 10c with NP19 (a small molecule PD-L1 inhibitor discovered by us before) decreased tumour burden substantially (TGI% = 60.1%) as compared to monotherapy groups. Moreover, the combination of 10c with NP19 enhanced the anti-tumour immune response, mediated by a decrease of PD-L1 expression levels and increased infiltration of anti-tumour CD8+ T cells in tumour tissues. Collectively, 10c represents a novel HDAC6 inhibitor deserving further investigation as a potential anti-cancer agent.

Background and Aim: To assess the utility of ultrasonic markers like B-line score (LUS), diaphragm thickness (DT), thickening fraction (DTF), and excursion (DE) as predictors of weaning outcomes in children on mechanical ventilation (MV) after cardiac surgery. Methods: This was a prospective observational study done in postcardiac surgical intensive care unit (ICU) of a tertiary care hospital. Children aged 1 month to 18 years, on MV after cardiac surgery from January to November 2017, were included. They were extubated after satisfying institutional weaning criteria. Ultrasound for LUS, DT, DTF, and DE was performed preoperatively, during pressure support ventilation (PSV) before extubation and 4 h after extubation. Results: Patients were divided into weaning failure and success groups based on reintubation within 48 h of extubation. Of the 50 evaluated patients, 43 (86%) were weaned successfully and 7 (14%) had weaning failure. The left DTF during PSV was lower in patients weaning failure (0.00%, interquartile range (IQR) 0.00–14.28 vs 16.67%, IQR 8.33–22.20, P = 0. 012). The left DTF≤ 14.64% during PSV (area under receiver's operating curve 0.795, P = 0.014), 85% sensitivity, and 57% specificity (positive likelihood ratio 1.97, negative likelihood ratio 0.25) could predict weaning failure. Conclusion: The left DTF during PSV is a good predictor of weaning failure in children on MV in postoperative ICU after congenital cardiac surgery. Take home message In children on mechanical ventilation after cardiac surgery, left DTF during pressure support ventilation is a good predictor of weaning failure.

Background: Data on outcomes of coronavirus disease 2019 (COVID-19) in pregnancy are scarce, although they represent a unique physiological state affecting both the mother and child. We present collated data from a tertiary care center in North India, encompassing the outcome, clinical characteristics, and management of these patients. Materials and Methods: Parturients ≥ 18 years old, with COVID-19 reverse transcriptase polymerase chain reaction positive for severe acute respiratory syndrome coronavirus 2, requiring intensive care unit (ICU) admission at a tertiary care hospital were included. Data were retrospectively collected from April 2020 to November 2021. Results: In all, 26 parturients were admitted to ICU with COVID-19. Five patients were admitted during the first wave, and all were asymptomatic. Twenty-one patients presented during the second wave (March 2021 onward), among which four were asymptomatic and 17 symptomatic (all with severe pneumonia). Three patients presented in the second trimester, all with critical disease, out of which one did not survive. Two patients had twin gestation, and others were singleton pregnancies. Seven patients (27%) were primigravida, and five patients (19.2%) had more than third pregnancy. Twenty critically ill women (77%) delivered during the hospital stay. Six patients died during the second wave, and four deaths (66.7%) were because of COVID-19 acute respiratory distress syndrome (ARDS). Conclusions: The number of admissions and mortality related to COVID-19 ARDS was higher in the second wave than in the first. We report the safe use of remdesivir and tocilizumab in our patients.

Sorghum is a climate-resilient cereal and staple food crop for more than 200 million people in arid and semi-arid countries of Asia and Africa. Despite the economic importance, the productivity of sorghum in India is constrained by biotic and abiotic stresses such as incidences of shoot fly, grain mold and drought. Indian sorghum breeding focused on dual-purpose (grain and fodder), short-duration varieties with multiple resistance/tolerance to pests and diseases and improved nutritional quality (high protein, iron and zinc and low fat). In this context, it is important to ascertain the genetic progress made over 30 years by assessing the efficiency of past achievements in genetic yield potential and to facilitate future genetic improvement. The current study determined the genetic gain in 24 sorghum varieties developed by the national and state level research systems during 1990-2020. The 24 varieties were evaluated for three years (2018-2020) at six locations in Telangana state for yield, nutritional characteristics and tolerance to shoot fly and grain mold. The absolute grain yield genetic gain from the base year 1990 is 44.93 kg/ha/yr over the first released variety CSV 15. The realized mean yield increased from 2658 kg/ha of the variety CSV 15 in 1990s to 4069 kg/ha of SPV 2579 developed in 2020s. The absolute genetic gain for grain mold resistance is -0.11 per year with an overall relative gain of 1.46% over CSV 15. The top varieties for grain yield (SPV 2579, SPV 2678 and SPV 2578), fodder yield (PYPS 2, SPV 2769 and SPV 2679), shoot fly tolerance (PYPS 8, PYPS 2 and SPV 2179), mold tolerance (PYPS 8, PYPS 2 and SPV 2579) and high protein (PYPS 8, PYPS 2 and SPV 2769) were identified for possible scale up and further use in breeding program diversification. The study revealed that sorghum varieties bred with diverse genetic backgrounds such as landraces and with tolerance to pests and diseases had stable yield performance. Application of genomics and other precision tools can double genetic gains for these traits to strengthen sorghum cultivation in rainfed areas serving food and nutrition security.

This article discusses the impact of frontline demonstrations on red gram yield, economics, and yield gap analysis in Telangana. The study was conducted in different villages of Nalgonda and Yadadri Bhuvanagiri districts during the kharif season of 2018-19, 2019-20, and 2020-21. The results showed that the average red gram yield under the demonstration plot was higher compared to the farmer's practice, with an increase of 8.59%. The demonstration plot also had higher gross returns, net returns, and B:C ratio. The study suggests that adopting innovative approaches like large-scale demonstrations can further reduce the yield gap and increase farmers' income. The text discusses the results of Cluster Frontline Demonstrations conducted by the District Agricultural Advisory and Transfer of Technology Center (DAATTC) in Yadadri Bhuvanagiri. The demonstrations aimed to promote improved production technology for red gram (pigeon pea) cultivation. The results showed that the demonstrations, which included the use of high-yielding varieties, seed treatment, weed control, and pest control, resulted in higher yields and economic returns compared to farmers' practices. The demonstrations also helped create awareness and motivate non-beneficiary farmers to adopt improved practices. The study suggests the need for further research on cultivars, mechanization, and water conservation technologies. [Extracted from the article]