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AbstractThe present work proposes a suitable injection hole configuration of cylinder and laidback fan-shaped with forward and reverse direction for film cooling of a gas turbine blades application, based on experimental and numerical analysis. The experimental study is conducted for cylindrical hole at blowing ratio (1), injection angle (35°), and density ratio (1.2). The numerical study is performed for a wide range of operating parameters such as blowing ratios on (1-3), density ratios (2.42), mainstream flow Reynolds number as 4000 based on the hydraulic diameter of wind tunnel channel and, injection angle (35°) with the effect of forward and reverse injection of laidback fan shaped. The present study reveals that the formation of kidney vortices mitigated for reverse-shaped holes (secondary air is injected such that its axial velocity component is in the reverse direction to that of the mainstream) results in higher cooling performance with respect to forward-shaped holes. The coolant coverage is likewise more consistent and higher in the lateral direction compared to the forward injection. [ABSTRACT FROM AUTHOR]

Background & objectives: The tribal population in India is considered as one of the vulnerable groups with respect to their achievements in health and other developmental issues. In this context, this mapping review attempted to understand the health profile of the Tharu tribal community residing in the northern State of Uttar Pradesh, India through literature mining. Tharu tribe is one of the indigenous groups living in the Terai plain on the Indo-Nepal border. In 1967, this tribe was documented as a Scheduled Tribe by the Government of India. The present review aimed to map the health-seeking behaviour of the Tharu population and review other factors pertaining to their health such as socioeconomic, developmental, employment, education, etc. Methods: Online data search was carried out on PubMed and Google Scholar using search terms ‘Tharu’ AND ‘India’. In addition, official reports avaibale in public domain and grey literature was also searched. Results: Twenty seven studies including reviews, articles, books/book chapters were evaluated along with 13 reports (including reports from government organizations and grey literature) were retrieved and analyzed. Of the 27 published reports, 16 were found relevant to Tharu tribe in India. A total of 29 (16 articles + 13 reports ) were included in this review. Interpretation & Conclusions: This mapping review higheights the health seeking behaviour of the Tharu tribe in India that can help inform future interventions to improve the health status of the Tharu tribe as well as other aspects of their development. [ABSTRACT FROM AUTHOR]

Antibacterial and synergy potential of naturally occurring indole alkaloids (IA): 10-methoxy tetrahydroalstonine (1), isoreserpiline (2), 10 and 11 demethoxyreserpiline (3), reserpiline (4), serpentine (5), ajmaline (6), ajmalicine (7), yohimbine (8), and α-yohimbine (9) was evaluated using microbroth dilution assay. Further, α-yohimbine (9) was chemically transformed into six semisynthetic derivatives (9A-9F), and their antibacterial and synergy potential in combination with nalidixic acid (NAL) against E. coli strains CA8000 and DH5α were also evaluated. The IA 1, 2, 4, 5, 9 and the derivative 9F showed eightfold reduction in the MIC of NAL against the DH5α and four- to eightfold reduction against CA8000. These alkaloids also reduced MIC of another antibiotic, tetracycline up to 8folds, against the MDREC-KG4, a multidrug-resistant clinical isolate of E. coli. Mode of action study of these alkaloids showed efflux pumps inhibitory potential, which was supported by their in silico binding affinity and downregulation of efflux pump genes. These results may be of great help in the development of cost-effective antibacterial combinations for treating patients infected with multidrugresistant Gram-negative infections. [ABSTRACT FROM AUTHOR]

As a part of our drug discovery program, ursolic acid was chemically transformed into six semi-synthetic derivatives, which were evaluated for their antibacterial and drug resistance reversal potential in combination with conventional antibiotic nalidixic acid against the nalidixic acid-sensitive and nalidixic acid-resistant strains of Escherichia coli. Although ursolic acid and its all semi-synthetic derivatives did not show antibacterial activity of their own, but in combination, they significantly reduced the minimum inhibitory concentration of nalidixic acid up to eightfold. The 3- O-acetyl-urs-12-en-28-isopropyl ester (UA-4) and 3- O-acetyl-urs-12-en-28- n-butyl ester (UA-5) derivatives of ursolic acid reduced the minimum inhibitory concentration of nalidixic acid by eightfold against nalidixic acid-resistant and four and eightfold against nalidixic acid-sensitive, respectively. The UA-4 and UA-5 were further evaluated for their synergy potential with another antibiotic tetracycline against the multidrug-resistant clinical isolate of Escherichia coli- KG4. The results showed that both these derivatives in combination with tetracycline reduced the cell viability in concentration-dependent manner by significantly inhibiting efflux pump. This was further supported by the in silico binding affinity of UA-4 and UA-5 with efflux pump proteins. These ursolic acid derivatives may find their potential use as synergistic agents in the treatment of multidrug-resistant Gram-negative infections. [ABSTRACT FROM AUTHOR]

We explored the antibacterial potential (alone and combination) against multidrug resistant (MDR) Pseudomonas aeruginosa isolates KG-P2 using synthesized thieno[3,2- c ]pyran-2-ones in combination with different antibiotics. Out of 14 compounds, two compounds (3g and 3l) abridged the MIC of tetracycline (TET) by 16 folds. Compounds was killing the KG-P2 cells, in time dependent manner, lengthened post-antibiotic effect (PAE) of TET and found decreased the mutant prevention concentration (MPC) of TET. In ethidium bromide efflux experiment, two compounds repressed the drug transporter (efflux pumps) which is further supported by molecular docking of these compounds with efflux complex MexAB-OprM. In another study, these compounds inhibited the synthesis of biofilm. Gaurav Raj Dwivedi, Dharmendra K Yadav, Reeta Rai, Ramendra Pratap, Khusbu Singh, Sanghamitra Pati, Satya Narayan Sahu, Rajni Kant, and Mahendra P. Darokar [Display omitted] • Antibacterial potential (alone and combination) against MDR; Pseudomonas aeruginosa is explored. • Thieno[3,2- c ]pyran-2-ones was used in combination with different antibiotics. • Two compounds (3g and 3l) abridged the MIC of tetracycline (TET) by 16 folds. • Compounds was killing the KG-P2 cells, in time dependent manner, lengthened post-antibiotic effect (PAE) of TET. • In-silico docking of these compounds with efflux complex MexAB-OprM supported the result. [ABSTRACT FROM AUTHOR]

Acute encephalitis syndrome (AES) outbreaks in children of Eastern Uttar Pradesh (E-UP) region of India have been a longstanding public health issue, with a significant case fatality rate of 20–25%. Since past decade, a rise in chikungunya (CHIK) cases has been occurring, which is a reported etiology of AES. However, the burden of chikungunya virus (CHIKV) among pediatric AES (pAES) is unknown from E-UP. We included 238 hospitalized pAES cases. The presence of IgM antibodies for CHIKV, and Dengue virus (DENV) was tested, and RT-PCR was performed for CHIKV and DENV in serologically confirmed CHIKV and DENV pAES cases. Positive samples were sequenced using Sangers sequencing. Further, to check for co-infection, IgM antibodies for other AES etiologies including Japanese encephalitis virus (JEV), Leptospira and Orientia tsutsugamushi (OT) in serum were also investigated. IgM ELISA demonstrated 5.04% (12) positivity for CHIKV. Among CHIKV IgM positive, 3 (25%, 3/12) pAES patients died. CHIKV genome was detected in 3 pAES specimens. Among which, 2 CHIKV cases were also positive for OT DNA. Partially sequenced CHIKV were genotyped as ECSA. The overall finding indicates evidence of CHIKV infection with high case fatality among pAES patients from E-UP. This study advocates constant serological and molecular surveillance of CHIKV in AES endemic regions of India. [ABSTRACT FROM AUTHOR]

Scrub typhus (ST) caused by Orientia tsutsugamushi (OT), has long been known to cause acute encephalitis syndrome (AES) and acute febrile illness (AFI). The immunodominant 56 kDa protein of OT, which is encoded by the 56 kDa gene (1600 bp encoding 516–541 amino acids) is a commonly studied antigen for genotype and serotype assignment. Previous studies from India have utilized partial type specific antigen (TSA) 56 kDa sequences for OT strain characterisation. On the other hand, understanding the antigenic diversity of current OT strains, is critical for developing specific diagnostic tests and vaccines against ST. As a result, the current study analyses antigenic variants using the entire TSA56 ORF of OT from AES cases. Phylogenetic investigation using complete TSA56 ORF sequences revealed Karp and Gilliam were the circulating predominant strains of OT. Furthermore, Immuno-informatical analysis demonstrated that the majority of high-binding affinity CD4 TCEs against the most prevalent Indian human leukocyte antigen alleles were present in the S-VDIII/IV and S-VDIV spacer regions of TSA56 ORF. TSA56 conserved spacer is crucial for OT immunological response investigations. Further, the pathophysiological effects of spacer domains in ST require further investigation. Furthermore, the characterization of the TSA56 spacer region of the OT from different parts of India is critical for developing region-specific ST diagnostic assays and vaccines. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the frequency distribution of different anatomical positions, and to measure the diameter, wall thickness, and length of appendix in patients with non-appendicular symptoms. Material and methods: This retrospective observational study was conducted among 1,575 patients, who had under-gone computed tomography (CT) scan of abdomen for various non-appendicular signs and symptoms. Frequency of distribution of different anatomic locations and measurements of various morphologic parameters were recorded. Results: The most common location of appendix was retrocecal, followed by sub-cecal, post-ileal, and pelvic locations. The mean length of appendix was 66.7 mm (range, 6.3-123 mm), and the diameter was 6.3 mm (range, 2.8-11.3 mm). Diameter of > 6 mm was noted in 48.12% patients. The mean wall thickness was 2.37 mm, ranging 1.2-4.2 mm. The most common intra-luminal content was air-mixed with hypodense or hyperdense material observed in 70.5% of cases. Conclusions: Although an appendix with diameter less than 6 mm may be considered normal, a diameter above 6 mm has an overlap between a normal and inflamed appendix. Therefore, it should be considered in association with clinical and secondary findings to avoid overdiagnosis and unnecessary appendicectomies. We strongly recommend that diameter-based CT criteria to diagnose appendicitis should be revised and standardized. [ABSTRACT FROM AUTHOR]

There are several bacteria called superbugs that are resistant to multiple antibiotics which can be life threatening specially for critically ill and hospitalized patients. This article provides up-to-date treatment strategies employed against some major superbugs, like methicillin-resistant Staphylococcus aureus, carbapenem-resistant Enterobacteriaceae, vancomycin-resistant Enterococcus, multidrug-resistant Pseudomonas aeruginosa, and multidrug-resistant Escherichia coli. The pathogen-directed therapeutics decrease the toxicity of bacteria by altering their virulence factors by specific processes. On the other hand, the host-directed therapeutics limits these superbugs by modulating immune cells, enhancing host cell functions, and modifying disease pathology. Several new antibiotics against the global priority superbugs are coming to the market or are in the clinical development phase. Medicinal plants possessing potent secondary metabolites can play a key role in the treatment against these superbugs. Nanotechnology has also emerged as a promising option for combatting them. There is urgent need to continuously figure out the best possible treatment strategy against these superbugs as resistance can also be developed against the new and upcoming antibiotics in future. Rational use of antibiotics and maintenance of proper hygiene must be practiced among patients. [ABSTRACT FROM AUTHOR]

Background: India began COVID-19 vaccination in January 2021, initially targeting healthcare and frontline workers. The vaccination strategy was expanded in a phased manner and currently covers all individuals aged 18 years and above. India experienced a severe second wave of COVID-19 during March-June 2021. We conducted a fourth nationwide serosurvey to estimate prevalence of SARS-CoV-2 antibodies in the general population aged ≥6 years and healthcare workers (HCWs).Methods and Findings: We did a cross-sectional study between 14 June and 6 July 2021 in the same 70 districts across 20 states and 1 union territory where 3 previous rounds of serosurveys were conducted. From each district, 10 clusters (villages in rural areas and wards in urban areas) were selected by the probability proportional to population size method. From each district, a minimum of 400 individuals aged ≥6 years from the general population (40 individuals from each cluster) and 100 HCWs from the district public health facilities were included. The serum samples were tested for the presence of IgG antibodies against S1-RBD and nucleocapsid protein of SARS-CoV-2 using chemiluminescence immunoassay. We estimated the weighted and test-adjusted seroprevalence of IgG antibodies against SARS-CoV-2, along with 95% CIs, based on the presence of antibodies to S1-RBD and/or nucleocapsid protein. Of the 28,975 individuals who participated in the survey, 2,892 (10%) were aged 6-9 years, 5,798 (20%) were aged 10-17 years, and 20,285 (70%) were aged ≥18 years; 15,160 (52.3%) participants were female, and 21,794 (75.2%) resided in rural areas. The weighted and test-adjusted prevalence of IgG antibodies against S1-RBD and/or nucleocapsid protein among the general population aged ≥6 years was 67.6% (95% CI 66.4% to 68.7%). Seroprevalence increased with age (p < 0.001) and was not different in rural and urban areas (p = 0.822). Compared to unvaccinated adults (62.3%, 95% CI 60.9% to 63.7%), seroprevalence was significantly higher among individuals who had received 1 vaccine dose (81.0%, 95% CI 79.6% to 82.3%, p < 0.001) and 2 vaccine doses (89.8%, 95% CI 88.4% to 91.1%, p < 0.001). The seroprevalence of IgG antibodies among 7,252 HCWs was 85.2% (95% CI 83.5% to 86.7%). Important limitations of the study include the survey design, which was aimed to estimate seroprevalence at the national level and not at a sub-national level, and the non-participation of 19% of eligible individuals in the survey.Conclusions: Nearly two-thirds of individuals aged ≥6 years from the general population and 85% of HCWs had antibodies against SARS-CoV-2 by June-July 2021 in India. As one-third of the population is still seronegative, it is necessary to accelerate the coverage of COVID-19 vaccination among adults and continue adherence to non-pharmaceutical interventions. [ABSTRACT FROM AUTHOR]

• By December 2020, 24.1% of the general population in India had been exposed to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). • For every case of coronavirus disease 2019 detected, there were 27 infections. • Seroprevalence was higher in urban areas compared with rural areas. • By December 2020, 25.6% healthcare workers had evidence of SARS-CoV-2 infection. Earlier serosurveys in India revealed seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) of 0.73% in May–June 2020 and 7.1% in August–September 2020. A third serosurvey was conducted between December 2020 and January 2021 to estimate the seroprevalence of SARS-CoV-2 infection among the general population and healthcare workers (HCWs) in India. The third serosurvey was conducted in the same 70 districts as the first and second serosurveys. For each district, at least 400 individuals aged ≥10 years from the general population and 100 HCWs from subdistrict-level health facilities were enrolled. Serum samples from the general population were tested for the presence of immunoglobulin G (IgG) antibodies against the nucleocapsid (N) and spike (S1-RBD) proteins of SARS-CoV-2, whereas serum samples from HCWs were tested for anti-S1-RBD. Weighted seroprevalence adjusted for assay characteristics was estimated. Of the 28,598 serum samples from the general population, 4585 (16%) had IgG antibodies against the N protein, 6647 (23.2%) had IgG antibodies against the S1-RBD protein, and 7436 (26%) had IgG antibodies against either the N protein or the S1-RBD protein. Weighted and assay-characteristic-adjusted seroprevalence against either of the antibodies was 24.1% [95% confidence interval (CI) 23.0–25.3%]. Among 7385 HCWs, the seroprevalence of anti-S1-RBD IgG antibodies was 25.6% (95% CI 23.5–27.8%). Nearly one in four individuals aged ≥10 years from the general population as well as HCWs in India had been exposed to SARS-CoV-2 by December 2020. [ABSTRACT FROM AUTHOR]

Background The factors responsible for seizure recurrence in patients with Solitary calcified neurocysticercosis (NCC) are not well understood. Blood brain barrier (BBB) breach may be associated with seizure recurrence. Dynamic contrast enhanced (DCE) MRI derived indices k ep, k trans and v e are useful in quantifying BBB permeability. In this study, we assessed the possible role of DCE-MRI and matrix metalloproteinases (MMP)-9 levels in predicting seizure recurrence. Methods In this prospective-observational study, patients with new-onset seizures and a solitary calcified NCC were included. DCE-MRI was done to quantify BBB integrity. DCE-MRI parameters were measured as k ep , k trans and v e . MMP-9 levels were estimated. Patients were followed for 1 year, when DCE-MRI and MMP-9 levels were repeated. Patients were classified into two groups on the basis of seizure recurrence, which was defined as the recurrence of an episode of seizure at least 1 week after the initiation of the anti-epileptic drugs. Logistic regression analysis was done. Results At 1-year of follow up, 8 out of 32 patients had seizure recurrence. Baseline DCE-MRI derived k ep (p = 0.015) and MMP-9 levels (p = 0.019) were significantly higher in the seizure “recurrence” group compared with the “no recurrence” group. On within-group analysis, a significant increase in k ep (p = 0.012), v e (p = 0.012), and MMP-9 levels (p = 0.017) was observed in the seizure “recurrence” group while a decrease was seen in v e and MMP-9 levels in the “no recurrence” group. Conclusion Higher values of DCE-MRI indices and MMP-9 levels, with a corresponding trend in the follow-up, can be useful in predicting lesions with a higher propensity for seizure recurrence. [ABSTRACT FROM AUTHOR]

Background Cerebrospinal fluid (CSF) is an essential bio-fluid of the central nervous system (CNS), playing a vital role in the protection of CNS and performing neuronal function regulation. The chemical composition of CSF varies during onset of meningitis, neurodegenerative disorders (positive controls) and in traumatic cases (negative controls). Methods The study design was broadly categorized into meningitis cases, negative controls and positive controls. Further differentiation among the three groups was carried out using Principal Component Analysis (PCA) followed by supervised Partial Least Square Discriminant Analysis (PLS-DA). Results The statistical analysis of meningitis vs. negative controls using PLS-DA model resulted in R 2 of 0.97 and Q 2 of 0.85. There was elevation in the levels of ketone bodies, total free amino acids, glutamine, creatine, citrate and choline containing compounds (choline and GPC) in meningitis cases. Similarly, meningitis vs. positive controls resulted in R 2 of 0.80 and Q 2 of 0.60 and showed elevation in the levels of total free amino acids, glutamine, creatine/creatinine and citrate in the meningitis group. Four cases of HIV were identified by PLS-DA model as well as by clinical investigations. Conclusion On the basis of metabolic profile it was found that negative control CSF samples are more appropriate for differentiation of meningitis than positive control CSF samples. [ABSTRACT FROM AUTHOR]

Bacteria employ numerous resistance mechanisms against structurally distinct drugs by the process of multidrug resistance. A study was planned to discover the antibacterial potential of a graphene oxide nanosheet (GO), a graphene oxide–zinc oxide nanocomposite (GO/ZnO), a graphene oxide-chitosan nanocomposite (GO–CS), a zinc oxide decorated graphene oxide–chitosan nanocomposite (GO–CS/ZnO), and zinc oxide nanoparticles (ZnO) alone and in a blend with antibiotics against a PS-2 isolate of Pseudomonas aeruginosa. These nanocomposites reduced the MIC of tetracycline (TET) from 16 folds to 64 folds against a multidrug-resistant clinical isolate. Efflux pumps were interfered, as evident by an ethidium bromide synergy study with nanocomposites, as well as inhibiting biofilm synthesis. These nanoparticles/nanocomposites also decreased the mutant prevention concentration (MPC) of TET. To the best of our knowledge, this is the first report on nanomaterials as a synergistic agent via inhibition of efflux and biofilm synthesis. [ABSTRACT FROM AUTHOR]

DbMDR is non-redundant reference database of multidrug resistance (MDR) genes and their orthologs acting as potential drug targets. Drug resistance is a common phenomenon of pathogens, creating a serious problem of inactivation of drugs and antibiotics resulting in occurrence of diseases. Apart from other factors, the MDR genes present in pathogens are shown to be responsible for multidrug resistance. Much of the unorganized information on MDR genes is scattered across the literature and other web resources. Thus, consolidation of such knowledge about MDR genes into one database will make the drug discovery research more efficient. Mining of text for MDR genes has resulted into a large number of publications but in scattered and unorganized form. This information was compiled into a database, which enables a user not only to look at a particular MDR gene but also to find out putative homologs based on sequence similarity, conserved domains, and motifs in proteins encoded by MDR genes more efficiently. At present, DbMDR database contains 2843 MDR genes characterized experimentally as well as functionally annotated with cross-referencing search support. The DbMDR database () is a comprehensive resource for comparative study focused on MDR genes and metabolic pathway efflux pumps and intended to provide a platform for researchers for further research in drug resistance. [ABSTRACT FROM AUTHOR]