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Not AvailableLength-weight relationship and condition factor in 57 freshwater fish species of 19 families and 38 genera from various rivers, and lakes of different climatic zones in India were studied. The estimates (total 67) for the parameter b of the length-weight relationship ranged between 1.422 and 3.917, with a mean value of 2.994. Correlation coefficient was found to be highly significant (r2 >0.90) in all except for Crossocheilus latius latius, Acanthocobitis botia and Garra lamta. Growth was found to be isometric (b = 3) in 32 species, positively allometric (b>3) in 21 species and negatively allometric (b<3) in 14 species. It was also found that some species exhibited variations in their growth pattern in different habitats, which showed the influence of preference and availability of suitable habitat conditions.NAIP-GEF (National Agricultural Innovative Projects-Global Environment Fund), New Delhi, India, for providing financial assistance

Experience of establishing and coordinating a nationwide network for bidirectional intussusception surveillance in India: lessons for multisite research studies

Objectives To document and share the process of establishing the nationally representative multisite surveillance network for intussusception in India, coordination, data management and lessons learnt from the implementation.Design This study combined both retrospective and prospective surveillance approaches.Setting 19 tertiary care institutions were selected in India considering the geographic representation and public and private mixParticipants All children under-2 years of age with intussusceptionPrimary and secondary outcome measures The experience of site selection, regulatory approvals, data collection, quality assurance and network coordination were documented.Results The site selection process involved systematic and objective four steps including shortlisting of potential institutions, information seeking and telephonic interaction, site visits and site selection using objective criteria. Out of over 400 hospitals screened across India, 40 potential institutions were shortlisted and information was sought by questionnaire and interaction with investigators. Out of these, 25 institutes were visited and 19 sites were finally selected to participate in the study. The multistep selection process allowed filtering and identification of sites with adequate capacity and motivated investigators. The retrospective surveillance documented 1588 cases (range: 14–652 cases/site) and prospective surveillance recruited 621 cases (range: 5–191 cases/site). The multilayer quality assurance measures monitored and ensured protocol adherence, complete record retrieval and data completeness. The key challenges experienced included time taken for obtaining regulatory and ethical approvals, which delayed completion of the study. Ten sites continued with another multisite vaccine safety surveillance study.Conclusion The experience and results of this systematic and objective site selection method in India are promising. The systematic multistep site selection and data quality assurance methods presented here are feasible and practical. The lessons from the establishment and coordination of this surveillance network can be useful in planning, selecting the sites and conducting multisite and surveillance studies in India and developing countries

Association of meteorological parameters with intussusception in children aged under 2 years: results from a multisite bidirectional surveillance over 7 years in India

Objectives The study aimed to document the association between intussusception in Indian children and meteorological parameters and examine regional variations.Design A bidirectional (retrospective and prospective) surveillance between July 2010 and September 2017.Setting At 20 hospitals in India, retrospective case record review during July 2010 and March 2016 and prospective surveillance during April 2016 and September 2017 were performed.Participants 2161 children aged 2–24 months with first intussusception episode were included.Interventions The monthly mean meteorological parameters (temperature, sunshine, rainfall, humidity and wind speed) for the study sites were collected.Methods The association between monthly intussusception cases and meteorological parameters was examined at pooled, regional and site levels using Pearson (r) and Spearman’s rank-order (ρ) correlation, factorial analysis of variance, and Poisson regression or negative binomial regression analyses.Results The intussusception cases were highest in summer and lowest in autumn seasons. Pearson correlation analysis showed that temperature (r=0.056; p&lt;0.05), wind speed (r=0.134; p&lt;0.01) and humidity (r=0.075; p&lt;0.01) were associated with monthly intussusception cases. Spearman’s rank-order correlation analysis found that temperature (ρ=0.049; p&lt;0.05), wind speed (ρ=0.096; p&lt;0.01) and sunshine (ρ=0.051; p&lt;0.05) were associated with monthly intussusception cases. Poisson regression analysis resulted that monthly intussusception case was associated with rising temperature (North region, p&lt;0.01 and East region, p&lt;0.05), sunshine (North region, p&lt;0.01), humidity (East region, p&lt;0.01) and wind speed (East region, p&lt;0.01). Factorial analysis of variance revealed a significant seasonal difference in intussusception cases for pooled level (p&lt;0.05), 2–6 months age group (p&lt;0.05) and North region (p&lt;0.01). Significant differences in intussusception cases between summer and autumn seasons were observed for pooled (p&lt;0.01), children aged 2–6 months (p&lt;0.05) and 7–12 months (p&lt;0.05).Conclusions Significant correlations between intussusception cases and temperature, humidity, and wind speed were observed at pooled and regional level in India. A peak in summer months was noted, which may be used for prediction, early detection and referral for appropriate management of intussusception

Lead Optimization of 1,4-Azaindoles as Antimycobacterial Agents

In a previous report, we described the discovery of 1,4-azaindoles, a chemical series with excellent in vitro and in vivo antimycobacterial potency through noncovalent inhibition of decaprenylphosphoryl-β-d-ribose-2′-epimerase (DprE1). Nevertheless, high mouse metabolic turnover and phosphodiesterase 6 (PDE6) off-target activity limited its advancement. Herein, we report lead optimization of this series, culminating in potent, metabolically stable compounds that have a robust pharmacokinetic profile without any PDE6 liability. Furthermore, we demonstrate efficacy for 1,4-azaindoles in a rat chronic TB infection model. We believe that compounds from the 1,4-azaindole series are suitable for in vivo combination and safety studies

4-Aminoquinolone Piperidine Amides: Noncovalent Inhibitors of DprE1 with Long Residence Time and Potent Antimycobacterial Activity

4-Aminoquinolone piperidine amides (AQs) were identified as a novel scaffold starting from a whole cell screen, with potent cidality on Mycobacterium tuberculosis (Mtb). Evaluation of the minimum inhibitory concentrations, followed by whole genome sequencing of mutants raised against AQs, identified decaprenylphosphoryl-beta-D-ribose 2'-epimerase (DprE1) as the primary target responsible for the antitubercular activity. Mass spectrometry and enzyme kinetic studies indicated that AQs are noncovalent, reversible inhibitors of DprE1 with slow on rates and long residence times of similar to 100 min on the enzyme. In general, AQs have excellent leadlike properties and good in vitro secondary pharmacology profile. Although the scaffold started off as a single active compound with moderate potency from the whole cell screen, structure-activity relationship optimization of the scaffold led to compounds with potent DprE1 inhibition (IC50 < 10 nM) along with potent cellular activity (MIC = 60 nM) against Mtb

Thiazolopyridine Ureas as Novel Antitubercular Agents Acting through Inhibition of DNA Gyrase B

A pharmacophore-based search led to the identification of thiazolopyridine ureas as a novel scaffold with antitubercular activity acting through inhibition of DNA Gyrase B (GyrB) ATPase. Evaluation of the binding mode of thiazolopyridines in a Mycobacterium tuberculosis (Mtb) GyrB homology model prompted exploration of the side chains at the thiazolopyridine ring C-5 position to access the ribose/solvent pocket. Potent compounds with GyrB IC₅₀ ≤ 1 nM and Mtb MIC ≤ 0.1 μM were obtained with certain combinations of side chains at the C-5 position and heterocycles at the C-6 position of the thiazolopyridine core. Substitutions at C-5 also enabled optimization of the physicochemical properties. Representative compounds were cocrystallized with Streptococcus pneumoniae (Spn) ParE; these confirmed the binding modes predicted by the homology model. The target link to GyrB was confirmed by genetic mapping of the mutations conferring resistance to thiazolopyridine ureas. The compounds are bactericidal in vitro and efficacious in vivo in an acute murine model of tuberculosis