DETERMINATION OF BIOACTIVE COMPONENTS OF BARLERIA COURTALLICA NEES (ACANTHACEAE) BY GAS CHROMATOGRAPHY–MASS SPECTROMETRY ANALYSIS

Objective: The present investigation was carried out to determine the possible bioactive components of stem, root, and leaf of Barleria courtallica Nees using a gas chromatography–mass spectrometry (GC-MS).Methods: The phytocomponents of the ethanol extracts of stem, root, and leaf of B. courtallica were investigated using PerkinElmer GC-MS, while the mass spectra of the compounds found in the extracts were matched with the National Institute of Standards and Technology version II library. Results: 25, 23, and 28 compounds were identified in the ethanol extracts of stem, root, and leaf of B. courtallica, respectively. The prevailing compounds of stem were β-sitosterol (20.27%), stigmasterol (17.07%), eicosane, 7-hexyl- (6.64%), 3,7,11,15-tetramethyl-2-hexadecan-1-ol (5.97%), and tetracosane, 11-decyl- (5.91%). The major constituents recorded from root extract of B. courtallica were β-sitosterol (22.94%), stigmasterol (20.17%), urs-12-en-28-oic acid, 3-hydroxy-, methyl ester, (3β)- (18.42%), and eiosane, 7-hexyl- (7.06%). The prevailing compounds of leaf were 3,7,11,15- tetramethyl-2-hexadecan-1-ol (34.42%), phytol (14.18%), β-sitosterol (12.71%), squalene (11.25%), stigmasterol (8.15%), phytol acetate (6.53%). Conclusions: From the results, it is evident that B. courtallica contains various bioactive compounds and is recommended as a plant of phytopharmaceutical importance

HEPATOPROTECTIVE EFFECT OF HEDYOTIS LESCHENAULTIANA DC, ETHANOL EXTRACT IN CCL 4 INDUCED HEPATOTOXICITY IN WISTAR RATS

ABSTRACT Objective: The intention of this study is to explore the hepatoprotective potential of hepatoprotective potential of ethanol extract of Hedyotis leschenaultiana whole plant in carbon tetrachloride (CCl 4 ) induced hepatoprotective rats. Methods: Hepatotoxicity was induced in male wistar rats by intraperitoneal infection of CCl (2.5 ml/kg body weight for 14 days). The ethanol extract of H. leschenaultiana whole plant was administered to the experimental rats (100, 200, and 300 mg/kg body weight for 14 days). Silymarin (100 mg/kg) was given as a reference standard drug. In hepatotoxic rats, liver damage was studied by assessing parameters such as serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (ALP), total, conjugated and unconjugated bilirubin, gamma-glutamyl transferase, concentration of proteins, and antioxidants in serum. Results: Administration of hepatotoxins (CCl 4 4 ) showed significant elevation of SGOT, SGPT, serum ALP, total bilirubin, conjugated, unconjugated, and lipid peroxidation. Treatment with H. leschenaultiana (100, 200 and 300 mg/kg) significantly reduced the above-mentioned parameters. Regarding antioxidant activity, the ethanol extract of H. leschenaultiana exhibited a significant effect showing increasing levels of superoxide dismutase, catalase, glutathione peroxidase, reduced and glutathione, and glutathione reductase by reducing malondialdehyde levels. Conclusion: The ethanol extract of H. leschenaultiana have a significant effect on the CCl induced hepatotoxic animal models. Moreover, it is suggested that H. leschenaultiana can be used as a safe, cheap and effective alternative chemopreventive and protective against in the management of liver diseases. 4 Keywords: H. leschenaultiana, Bilirubins, Hepatotoxicity, Gamma-glutamyl transferase, Carbon tetrachloride, Melondialdehyde

Factors associated with routine childhood vaccine uptake and reasons for non-vaccination in India: 1998-2008.

Despite almost three decades of the Universal Immunization Program in India, a little more than half the children aged 12-23months receive the full schedule of routine vaccinations. We examined socio-demographic factors associated with partial-vaccination and non-vaccination and the reasons for non-vaccination among Indian children during 1998 and 2008. Data from three consecutive, nationally-representative, District Level Household and Facility Surveys (1998-99, 2002-04 and 2007-08) were pooled. Multinomial logistic regression was used to identify individual and household level socio-demographic variables associated with the child's vaccination status. The mother's reported reasons for non-vaccination were analyzed qualitatively, adapting from a previously published framework. The pooled dataset contained information on 178,473 children 12-23months of age; 53%, 32% and 15% were fully vaccinated, partially vaccinated and unvaccinated respectively. Compared with the 1998-1999 survey, children in the 2007-2008 survey were less likely to be unvaccinated (Adjusted Prevalence Odds Ratio (aPOR): 0.92, 95%CI=0.86-0.98) but more likely to be partially vaccinated (aPOR: 1.58, 95%CI=1.52-1.65). Vaccination status was inversely associated with female gender, Muslim religion, lower caste, urban residence and maternal characteristics such as lower educational attainment, non-institutional delivery, fewer antenatal care visits and non-receipt of maternal tetanus vaccination. The mother's reported reasons for non-vaccination indicated gaps in awareness, acceptance and affordability (financial and non-financial costs) related to routine vaccinations. Persisting socio-demographic disparities related to partial-vaccination and non-vaccination were associated with important childhood, maternal and household characteristics. Further research investigating the causal pathways through which maternal and social characteristics influence decision-making for childhood vaccinations is needed to improve uptake of routine vaccination in India. Also, efforts to increase uptake should address parental fears related to vaccination to improve trust in government health services as part of ongoing social mobilization and communication strategies

Transcultural Diabetes Nutrition Therapy Algorithm: The Asian Indian Application

India and other countries in Asia are experiencing rapidly escalating epidemics of type 2 diabetes (T2D) and cardiovascular disease. The dramatic rise in the prevalence of these illnesses has been attributed to rapid changes in demographic, socioeconomic, and nutritional factors. The rapid transition in dietary patterns in India—coupled with a sedentary lifestyle and specific socioeconomic pressures—has led to an increase in obesity and other diet-related noncommunicable diseases. Studies have shown that nutritional interventions significantly enhance metabolic control and weight loss. Current clinical practice guidelines (CPGs) are not portable to diverse cultures, constraining the applicability of this type of practical educational instrument. Therefore, a transcultural Diabetes Nutrition Algorithm (tDNA) was developed and then customized per regional variations in India. The resultant India-specific tDNA reflects differences in epidemiologic, physiologic, and nutritional aspects of disease, anthropometric cutoff points, and lifestyle interventions unique to this region of the world. Specific features of this transculturalization process for India include characteristics of a transitional economy with a persistently high poverty rate in a majority of people; higher percentage of body fat and lower muscle mass for a given body mass index; higher rate of sedentary lifestyle; elements of the thrifty phenotype; impact of festivals and holidays on adherence with clinic appointments; and the role of a systems or holistic approach to the problem that must involve politics, policy, and government. This Asian Indian tDNA promises to help guide physicians in the management of prediabetes and T2D in India in a more structured, systematic, and effective way compared with previous methods and currently available CPGs

Burden of typhoid and paratyphoid fever in India.

BACKGROUND: In 2017, more than half the cases of typhoid fever worldwide were projected to have occurred in India. In the absence of contemporary population-based data, it is unclear whether declining trends of hospitalization for typhoid in India reflect increased antibiotic treatment or a true reduction in infection. METHODS: From 2017 through 2020, we conducted weekly surveillance for acute febrile illness and measured the incidence of typhoid fever (as confirmed on blood culture) in a prospective cohort of children between the ages of 6 months and 14 years at three urban sites and one rural site in India. At an additional urban site and five rural sites, we combined blood-culture testing of hospitalized patients who had a fever with survey data regarding health care use to estimate incidence in the community. RESULTS: A total of 24,062 children who were enrolled in four cohorts contributed 46,959 child-years of observation. Among these children, 299 culture-confirmed typhoid cases were recorded, with an incidence per 100,000 child-years of 576 to 1173 cases in urban sites and 35 in rural Pune. The estimated incidence of typhoid fever from hospital surveillance ranged from 12 to 1622 cases per 100,000 child-years among children between the ages of 6 months and 14 years and from 108 to 970 cases per 100,000 person-years among those who were 15 years of age or older. Salmonella enterica serovar Paratyphi was isolated from 33 children, for an overall incidence of 68 cases per 100,000 child-years after adjustment for age. CONCLUSIONS: The incidence of typhoid fever in urban India remains high, with generally lower estimates of incidence in most rural areas. (Funded by the Bill and Melinda Gates Foundation; NSSEFI Clinical Trials Registry of India number, CTRI/2017/09/009719; ISRCTN registry number, ISRCTN72938224.)

A Novel Genetic Screen Implicates Elm1 in the Inactivation of the Yeast Transcription Factor SBF

BACKGROUND: Despite extensive large scale analyses of expression and protein-protein interactions (PPI) in the model organism Saccharomyces cerevisiae, over a thousand yeast genes remain uncharacterized. We have developed a novel strategy in yeast that directly combines genetics with proteomics in the same screen to assign function to proteins based on the observation of genetic perturbations of sentinel protein interactions (GePPI). As proof of principle of the GePPI screen, we applied it to identify proteins involved in the regulation of an important yeast cell cycle transcription factor, SBF that activates gene expression during G1 and S phase. METHODOLOGY/PRINCIPLE FINDINGS: The principle of GePPI is that if a protein is involved in a pathway of interest, deletion of the corresponding gene will result in perturbation of sentinel PPIs that report on the activity of the pathway. We created a fluorescent protein-fragment complementation assay (PCA) to detect the interaction between Cdc28 and Swi4, which leads to the inactivation of SBF. The PCA signal was quantified by microscopy and image analysis in deletion strains corresponding to 25 candidate genes that are periodically expressed during the cell cycle and are substrates of Cdc28. We showed that the serine-threonine kinase Elm1 plays a role in the inactivation of SBF and that phosphorylation of Elm1 by Cdc28 may be a mechanism to inactivate Elm1 upon completion of mitosis. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that GePPI is an effective strategy to directly link proteins of known or unknown function to a specific biological pathway of interest. The ease in generating PCA assays for any protein interaction and the availability of the yeast deletion strain collection allows GePPI to be applied to any cellular network. In addition, the high degree of conservation between yeast and mammalian proteins and pathways suggest GePPI could be used to generate insight into human disease

Drosophila Dynein Intermediate Chain Gene, Dic61B, Is Required for Spermatogenesis

This study reports the identification and characterization of a novel gene, Dic61B, required for male fertility in Drosophila. Complementation mapping of a novel male sterile mutation, ms21, isolated in our lab revealed it to be allelic to CG7051 at 61B1 cytogenetic region, since two piggyBac insertion alleles, CG7051c05439 and CG7051f07138 failed to complement. CG7051 putatively encodes a Dynein intermediate chain. All three mutants, ms21, CG7051c05439 and CG7051f07138, exhibited absolute recessive male sterility with abnormally coiled sperm axonemes causing faulty sperm individualization as revealed by Phalloidin staining in Don Juan-GFP background. Sequencing of PCR amplicons uncovered two point mutations in ms21 allele and confirmed the piggyBac insertions in CG7051c05439 and CG7051f07138 alleles to be in 5′UTR and 4th exon of CG7051 respectively, excision of which reverted the male sterility. In situ hybridization to polytene chromosomes demonstrated CG7051 to be a single copy gene. RT-PCR of testis RNA revealed defective splicing of the CG7051 transcripts in mutants. Interestingly, expression of cytoplasmic dynein intermediate chain, α, β, γ tubulins and α-spectrin was normal in mutants while ultra structural studies revealed defects in the assembly of sperm axonemes. Bioinformatics further highlighted the homology of CG7051 to axonemal dynein intermediate chain of various organisms, including DNAI1 of humans, mutations in which lead to male sterility due to immotile sperms. Based on these observations we conclude that CG7051 encodes a novel axonemal dynein intermediate chain essential for male fertility in Drosophila and rename it as Dic61B. This is the first axonemal Dic gene of Drosophila to be characterized at molecular level and shown to be required for spermatogenesis

Child wasting and concurrent stunting in low- and middle-income countries

Sustainable Development Goal 2.2—to end malnutrition by 2030—includes the elimination of child wasting, defined as a weight-for-length z-score that is more than two standard deviations below the median of the World Health Organization standards for child growth 1. Prevailing methods to measure wasting rely on cross-sectional surveys that cannot measure onset, recovery and persistence—key features that inform preventive interventions and estimates of disease burden. Here we analyse 21 longitudinal cohorts and show that wasting is a highly dynamic process of onset and recovery, with incidence peaking between birth and 3 months. Many more children experience an episode of wasting at some point during their first 24 months than prevalent cases at a single point in time suggest. For example, at the age of 24 months, 5.6% of children were wasted, but by the same age (24 months), 29.2% of children had experienced at least one wasting episode and 10.0% had experienced two or more episodes. Children who were wasted before the age of 6 months had a faster recovery and shorter episodes than did children who were wasted at older ages; however, early wasting increased the risk of later growth faltering, including concurrent wasting and stunting (low length-for-age z-score), and thus increased the risk of mortality. In diverse populations with high seasonal rainfall, the population average weight-for-length z-score varied substantially (more than 0.5 z in some cohorts), with the lowest mean z-scores occurring during the rainiest months; this indicates that seasonally targeted interventions could be considered. Our results show the importance of establishing interventions to prevent wasting from birth to the age of 6 months, probably through improved maternal nutrition, to complement current programmes that focus on children aged 6–59 months

Causes and consequences of child growth faltering in low-resource settings

Growth faltering in children (low length for age or low weight for length) during the first 1,000 days of life (from conception to 2 years of age) influences short-term and long-term health and survival 1,2. Interventions such as nutritional supplementation during pregnancy and the postnatal period could help prevent growth faltering, but programmatic action has been insufficient to eliminate the high burden of stunting and wasting in low- and middle-income countries. Identification of age windows and population subgroups on which to focus will benefit future preventive efforts. Here we use a population intervention effects analysis of 33 longitudinal cohorts (83,671 children, 662,763 measurements) and 30 separate exposures to show that improving maternal anthropometry and child condition at birth accounted for population increases in length-for-age z-scores of up to 0.40 and weight-for-length z-scores of up to 0.15 by 24 months of age. Boys had consistently higher risk of all forms of growth faltering than girls. Early postnatal growth faltering predisposed children to subsequent and persistent growth faltering. Children with multiple growth deficits exhibited higher mortality rates from birth to 2 years of age than children without growth deficits (hazard ratios 1.9 to 8.7). The importance of prenatal causes and severe consequences for children who experienced early growth faltering support a focus on pre-conception and pregnancy as a key opportunity for new preventive interventions