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: In this paper from Basu and colleagues, a simulation of tobacco control and pharmacological interventions to prevent cardiovascular disease mortality in India predicted that Smokefree laws and increased tobacco taxation are likely to be the most effective measures to avert future cardiovascular deaths in India. Please see later in the article for the Editors' Summary [ABSTRACT FROM AUTHOR]

Context: Though the cardiovascular diseases are the leading cause of mortality in India, little is known about the human and economic loss attributed to the disease. The aim of this paper is to account the age and sex pattern of mortality, hospitalisation and the cost of hospitalisation for cardiovascular diseases in India. Data and Methods: Data for the present study has been drawn from multiple sources; 52nd and 60th rounds of the National Sample Survey, Special Survey of Death, 2001–03 and the Sample Registration System 2004–2010. Under the changing demographics and constant assumptions of mortality, hospitalisation and cost of hospitalisation, we have estimated the deaths, hospitalisation and cost of hospitalisation for cardiovascular diseases in India during 2004 to 2021. Descriptive analyses and multivariate techniques were used to understand the socio-economic differentials in cost of hospitalisation for cardiovascular diseases in India. Findings: In India, the cardiovascular diseases accounted for an estimated 1.4 million deaths in 2004 and it is likely to be 2.1 million in 2021. An estimated 6.7 million people were hospitalised for cardiovascular diseases in 2004, and projected to be 10.9 million by 2021. Unlike mortality, majority of the hospitalisation due to cardiovascular diseases will be in the prime working age group (25–59). The estimated cost of hospitalisation for cardiovascular diseases was 94/− billion rupees in 2004 and expected to be 152/− billion rupees by 2021, at 2004 prices. The cost of hospitalisation for cardiovascular diseases was significantly high in private health centres, high fertility states and among high socio-economic groups. Conclusion: The cardiovascular mortality and hospitalisation will be largely concentrated in the prime working age group and the cost of hospitalisation is expected to increase substantially in coming years. This calls for mobilising resources, increasing access to health insurance and devising strategies for the prevention, control and treatment of cardiovascular diseases in India. [ABSTRACT FROM AUTHOR]

Previously we reported that the exposure to hepatitis B virus (HBV) infection serves as a major threat among the treatment naive HIV infected population of eastern India. Hence, molecular characterization of these strains is of utmost importance in order to identify clinically significant HBV mutations. A total of 85 treatment naive HIV/HBV co-infected participants were included of whom the complete basal core promoter/precore region, the core and the whole envelope gene could be successfully sequenced for 59, 57 and 39 isolates respectively. Following phylogenetic analysis, it was found that HBV/D was the predominant genotype with HBV/D2 (38.5%) being the most prevalent subgenotype followed by HBV/A1. The major mutations affecting HBeAg expression includes the A1762T/G1764A (13.6%), G1896A (22%) and G1862T mutation (33.9%) which was predominantly associated with HBV/A1. Moreover, the prevalence of G1896A was considerably high among the HBeAg negative HIV/HBV co-infected subjects compared to HBV mono-infection. The main amino acid substitutions within the MHC class II restricted T-cell epitope of HBcAg includes the T12S (15.8%) and T67N (12.3%) mutation and the V27I (10.5%) mutation in the MHC class I restricted T-cell epitope. PreS1/S2 deletion was detected in 3 isolates with all harboring the BCP double mutation. Furthermore, the frequently occurring mutations in the major hydrophilic loop of the S gene include the T125M, A128V and M133I/L. Therefore, this study is the first from India to report useful information on the molecular heterogeneity of the HBV strains circulating among the treatment naive HIV/HBV co-infected population and is thus clinically relevant. [ABSTRACT FROM AUTHOR]

Background: Genetic variants in nicotinic acetylcholine receptor and alcohol metabolism genes have been associated with propensity to smoke tobacco and drink alcohol, respectively, and also implicated in genetic susceptibility to head and neck cancer. In addition to smoking and alcohol, tobacco chewing is an important oral cancer risk factor in India. It is not known if these genetic variants influence propensity or oral cancer susceptibility in the context of this distinct etiology. Methods: We examined 639 oral and pharyngeal cancer cases and 791 controls from two case-control studies conducted in India. We investigated six variants known to influence nicotine addiction or alcohol metabolism, including rs16969968 (CHRNA5), rs578776 (CHRNA3), rs1229984 (ADH1B), rs698 (ADH1C), rs1573496 (ADH7), and rs4767364 (ALDH2). Results: The CHRN variants were associated with the number of chewing events per day, including in those who chewed tobacco but never smoked (P =  0.003, P =  0.01 for rs16969968 and rs578776 respectively). Presence of the variant allele contributed to approximately 13% difference in chewing frequency compared to non-carriers. While no association was observed between rs16969968 and oral cancer risk (OR =  1.01, 95% CI =  0.83– 1.22), rs578776 was modestly associated with a 16% decreased risk of oral cancer (OR =  0.84, 95% CI =  0.72– 0.98). There was little evidence for association between polymorphisms in genes encoding alcohol metabolism and oral cancer in this population. Conclusion: The association between rs16969968 and number of chewing events implies that the effect on smoking propensity conferred by this gene variant extends to the use of smokeless tobacco. [ABSTRACT FROM AUTHOR]

Expression of matrix metalloproteinase-1 (MMP-1), an interstitial collagenase, plays a major role in cellular invasion during development of gastric cancer, a leading cause of death worldwide. A single-nucleotide polymorphism (SNP) −1607 1G/2G site of the MMP-1 gene promoter has been reported to alter transcription level. While the importance’s of other SNPs in the MMP-1 promoter have not yet been studied in gastric cancer, our aim was to investigate MMP-1 gene promoter polymorphisms and gastric cancer susceptibility in eastern Indian population. A total of 145 gastric cancer patients and 145 healthy controls were genotyped for MMP-1 −1607 1G/2G (rs1799750) by PCR-restriction fragment length polymorphism (RFLP), while MMP-1 −519 A/G (rs1144393), MMP-1 −422 T/A (rs475007), MMP-1 −340 T/C (rs514921) and MMP-1 −320 T/C (rs494379) were genotyped by DNA sequencing. A positive association was found with MMP-1 −422 T/A SNP that showed significant risk for regional lymph node metastasis (P = 0.021, Odd’s ratio (OR) = 3.044, Confidence intervals (CI) = 1.187–7.807). In addition, we found a significant association with lower stomach tumor formation among gastric cancer patients for three adjacent polymorphisms near the transcriptional start sites of [MMP-1 −422 T/A (P = 0.043, OR = 2.182, CI = 1.03–4.643), MMP-1 −340 T/C (P = 0.075, OR = 1.97, CI = 0.94–4.158) and MMP-1 −320 T/C (P = 0.034, OR = 2.224, CI = 1.064–40731)]. MMP-1 level in patients’ serum was correlated with MMP-1 promoter haplotypes conferring these three SNPs to evaluate the functional importance of these polymorphisms in lower stomach tumor formation and significant correlation was observed. Furthermore, MMP-1 −519 A/G polymorphism displayed poor cellular differentiation (P = 0.024, OR = 3.8, CI = 1.69–8.56) attributing a higher risk of cancer progression. In conclusion, MMP-1 proximal promoter SNPs are associated with the risk of lower stomach tumor formation and node metastasis in eastern Indian population. [ABSTRACT FROM AUTHOR]

Hanuman langur is one of the widely distributed and extensively studied non-human diurnal primates in India. Until recently it was believed to be a single species - Semnopithecus entellus. Recent molecular and morphological studies suggest that the Hanuman langurs consists of at least three species S. entellus, S. hypoleucos and S. priam. Furthermore, morphological studies suggested that both S. hypoleucos and S. priam have at least three subspecies in each. We explored the use of ecological niche modeling (ENM) to confirm the validity of these seven taxa and an additional taxon S. johnii belonging to the same genus. MaxEnt modeling tool was used with 19 bioclimatic, 12 vegetation and 6 hydrological environmental layers. We reduced total environmental variables to 14 layers after testing for collinearity and an independent test for model prediction was done using ENMTools. A total of 196 non-overlapping data points from primary and secondary sources were used as inputs for ENM. Results showed eight distinct ecological boundaries, corroborating the eight taxa mentioned above thereby confirming validity of these eight taxa. The study, for the first time provided ecological variables that determined the ecological requirements and distribution of members of the Hanuman langur species complex in the Indian peninsula. [ABSTRACT FROM AUTHOR]

There is increasing interest in the role of asymptomatic infection in transmission of Visceral Leishmaniasis (VL). We studied the individual, household and environmental factors associated with asymptomatic Leishmania donovani infected individuals and VL. 7,538 individuals living in VL endemic villages in India and Nepal were divided into three mutually exclusive groups based on their VL history and Direct Agglutination Test (DAT) results in yearly serosurveys over a two-year period. The groups were (1) VL cases, (2) asymptomatically infected individuals (seroconverters) and (3) seronegative individuals. VL cases and seroconverters were compared to seronegative individuals in mixed logistic regression models. The risk of seroconversion and disease was significantly increased in individuals aged 14 to 24 years old and by the presence of other DAT-positive, asymptomatically infected individuals and VL cases in the house. The risk of seroconversion was higher in Indian than in Nepalese villages and it increased significantly with age, but not so for VL. This study demonstrates that, when risk factors for leishmanial infection and VL disease are evaluated in the same population, epidemiological determinants for asymptomatic infection and VL are largely similar. [ABSTRACT FROM AUTHOR]

Transcriptome sequencing using Illumina RNA-seq was performed on populations of black tiger shrimp from India. Samples were collected from (i) four landing centres around the east coastline (EC) of India, (ii) survivors of a severe WSSV infection during pond culture (SUR) and (iii) the Andaman Islands (AI) in the Bay of Bengal. Equal quantities of purified total RNA from homogenates of hepatopancreas, muscle, nervous tissue, intestinal tract, heart, gonad, gills, pleopod and lymphoid organs were combined to create AI, EC and SUR pools for RNA sequencing. De novo transcriptome assembly resulted in 136,223 contigs (minimum size 100 base pairs, bp) with a total length 61 Mb, an average length of 446 bp and an average coverage of 163× across all pools. Approximately 16% of contigs were annotated with BLAST hit information and gene ontology annotations. A total of 473,620 putative SNPs/indels were identified. An Illumina iSelect genotyping array containing 6,000 SNPs was developed and used to genotype 1024 offspring belonging to seven full-sibling families. A total of 3959 SNPs were mapped to 44 linkage groups. The linkage groups consisted of between 16–129 and 13–130 markers, of length between 139–10.8 and 109.1–10.5 cM and with intervals averaging between 1.2 and 0.9 cM for the female and male maps respectively. The female map was 28% longer than the male map (4060 and 2917 cM respectively) with a 1.6 higher recombination rate observed for female compared to male meioses. This approach has substantially increased expressed sequence and DNA marker resources for tiger shrimp and is a useful resource for QTL mapping and association studies for evolutionarily and commercially important traits. [ABSTRACT FROM AUTHOR]

Mutations in the autosomal genes TMPRSS3, TMC1, USHIC, CDH23 and TMIE are known to cause hereditary hearing loss. To study the contribution of these genes to autosomal recessive, non-syndromic hearing loss (ARNSHL) in India, we examined 374 families with the disorder to identify potential mutations. We found four mutations in TMPRSS3, eight in TMC1, ten in USHIC, eight in CDH23 and three in TMIE. Of the 33 potentially pathogenic variants identified in these genes, 23 were new and the remaining have been previously reported. Collectively, mutations in these five genes contribute to about one-tenth of ARNSHL among the families examined. New mutations detected in this study extend the allelic heterogeneity of the genes and provide several additional variants for structure-function correlation studies. These findings have implications for early DNA-based detection of deafness and genetic counseling of affected families in the Indian subcontinent. [ABSTRACT FROM AUTHOR]

Background: In this study a large random collection (n = 2188) of facultative oligotrophic bacteria, from 90 water samples gathered in three consecutive years (2007–2009) from three different sampling sites of River Mahananda in Siliguri, West Bengal, India, were investigated for the presence of class 1 integrons and sequences of the amplification products. Methodology/Principal Findings: Replica plating method was employed for determining the antibiotic resistance profile of the randomly assorted facultative oligotrophic isolates. Genomic DNA from each isolate was analyzed by PCR for the presence of class 1 integron. Amplicons were cloned and sequenced. Numerical taxonomy and 16S rRNA gene sequence analyses were done to ascertain putative genera of the class 1 integron bearing isolates. Out of 2188 isolates, 1667 (76.19%) were antibiotic-resistant comprising of both single-antibiotic resistance (SAR) and multiple-antibiotic resistant (MAR), and 521 (23.81%) were sensitive to all twelve different antibiotics used in this study. Ninety out of 2188 isolates produced amplicon(s) of varying sizes from 0.15 to 3.45 KB. Chi-square (χ2) test revealed that the possession of class 1 integron in sensitive, SAR and MAR is not equally probable at the 1% level of significance. Diverse antibiotic-resistance gene cassettes, aadA1, aadA2, aadA4, aadA5, dfrA1, dfrA5, dfrA7, dfrA12, dfrA16, dfrA17, dfrA28, dfrA30, dfr-IIe, blaIMP-9, aacA4, Ac-6′-Ib, oxa1, oxa10 and arr2 were detected in 64 isolates. The novel cassettes encoding proteins unrelated to any known antibiotic resistance gene function were identified in 26 isolates. Antibiotic-sensitive isolates have a greater propensity to carry gene cassettes unrelated to known antibiotic-resistance genes. The integron-positive isolates under the class Betaproteobacteria comprised of only two genera, Comamonas and Acidovorax of family Comamonadaceae, while isolates under class Gammaproteobacteria fell under the families, Moraxellaceae, Pseudomonadaceae, Aeromonadaceae and Enterobacteriaceae. Conclusions: Oligotrophic bacteria are good sources of novel genes as well as potential reservoirs of antibiotic resistance gene casettes. [ABSTRACT FROM AUTHOR]

Lepidium latifolium Linn. (perennial pepperweed) is one of the preferred phytofoods among cold arid region of Ladakh, India and its leaves contribute significantly to people's diet. This study was conducted to determine its nutritive value and antioxidant activity. Plant samples from three different locations were selected in the present study. Results showed that this plant is an excellent source of glucosinolates, notably sinigrin that is present in very high amount (∼70–90%). Its value ranged from 149 to 199 µg per g fresh weight. Fatty acid composition analysis showed that its leaves were abundant in unsaturated fatty acids, specifically linolenic acid (18∶3) whose percentage is about 50%. Higher glucose and crude protein along with higher nitrogen to sulfur ratio, supplements the nutritive value of this plant. Based on total phenol, flavanoids, free radical scavenging activity and DNA protective activity showed that this ecotype of perennial pepperweed contains high antioxidant properties. The percentage inhibition for O2− scavenging activity ranged from 41.3% to 83.9%. Higher content of phenols (26.89 to 50.51 mg gallic acid equivalents per g dry weight) and flavanoids (38.66 to 76.00 mg quercetin equivalents per g dry weight) in leaves could be responsible for the free radical scavenging activity of this plant. Depending upon the location of the plants, variations were observed in different activities. Based on the systematic evaluation in this study, preparations of Lepidium latifolium from Ladakh can be promoted as substitute to dietary requirements. [ABSTRACT FROM AUTHOR]

Background: Cystic echinococcosis (CE) caused by the Echinococcus granulosus, is a major public health problem worldwide, including India. The different genotypes of E. granulosus responsible for human hydatidosis have been reported from endemic areas throughout the world. However, the genetic characterization of E. granulosus infecting the human population in India is lacking. The aim of study was to ascertain the genotype(s) of the parasite responsible for human hydatidosis in North India. Methodology/Principal Findings: To study the transmission patterns of E. granulosus, genotypic analysis was performed on hydatid cysts obtained from 32 cystic echinococcosis (CE) patients residing in 7 different states of North India. Mitochondrial cytochrome c oxidase subunit1 (cox1) sequencing was done for molecular identification of the isolates. Most of the CE patients (30/32) were found to be infected with hydatid cyst of either G3 (53.1%) or G1 (40.62%) genotype and one each of G5 (cattle strain) and G6 (camel strain) genotype. Conclusions/Significance: These findings demonstrate the zoonotic potential of G1 (sheep strain) and G3 (buffalo strain) genotypes of E. granulosus as these emerged as predominant genotypes infecting the humans in India. In addition to this, the present study reports the first human CE case infected with G5 genotype (cattle strain) in an Asian country and presence of G6 genotype (camel strain) in India. The results may have important implications in the planning of control strategies for human hydatidosis. [ABSTRACT FROM AUTHOR]

Background: Influenza is vaccine-preventable; however, the burden of severe influenza in India remains unknown. We conducted a population-based study to estimate the incidence of laboratory confirmed influenza-associated hospitalizations in a rural community in western India. Methods: We conducted active surveillance for hospitalized patients with acute medical illnesses or acute chronic disease exacerbations in Pune during pandemic and post pandemic periods (May 2009–April 2011). Nasal and throat swabs were tested for influenza viruses. A community health utilization survey estimated the proportion of residents hospitalized with respiratory illness at non-study facilities and was used to adjust incidence estimates from facility-based surveillance. Results: Among 9,426 hospitalizations, 3,391 (36%) patients were enrolled; 665 of 3,179 (20.9%) tested positive for influenza. Of 665 influenza positives, 340 (51%) were pandemic A(H1N1)pdm09 and 327 (49%) were seasonal, including A/H3 (16%), A/H1 (3%) and influenza B (30%). The proportion of patients with influenza peaked during August 2009 (39%) and 2010 (42%). The adjusted annual incidence of influenza hospitalizations was 46.8/10,000 during pandemic and 40.5/10,000 during post-pandemic period with comparable incidence of A(H1N1)pdm09 during both periods (18.8 and 20.3, respectively). The incidence of both pH1N1 and seasonal hospitalized influenza disease was highest in the 5–29 year olds. Conclusions: We document the previously unrecognized burden of influenza hospitalization in a rural community following the emergence of influenza A(H1N1)pdm09 viruses in India. During peak periods of influenza activity circulation i.e during the monsoon period, 20% of all hospital admissions in the community had influenza positivity. These findings can inform development of influenza prevention and control strategies in India. [ABSTRACT FROM AUTHOR]

Introduction: The objectives of this study are to develop a summary measure of risky sexual practice and examine the factors associated with this among female sex workers (FSWs) in Karnataka, India. Materials and Methods: Data were drawn from special behavioral surveys (SBS) conducted in 2007 among 577 FSWs in two districts of Karnataka, India: Belgaum and Bangalore. FSWs were recruited using the two-stage probability sampling design. FSWs' sexual practice was considered risky if they reported inconsistent condom use with any sexual partner and reported experience of one of the following vulnerabilities to HIV risk: anal sex, alcohol consumption prior to sex and concurrent sexual relationships. Results: About 51% of FSWs had engaged in risky sexual practice. The odds of engaging in risky sex were higher among FSWs who were older (35+ years) than younger (18–25 years) (58% vs. 45%, Adjusted Odds Ratio (AOR): 2.0, 95% confidence interval (CI): 1.2–3.4), who were currently married than never married (61% vs. 51%, AOR: 4.8, 95% CI: 2.5–9.3), who were in sex work for 10+ years than those who were in sex work for less than five years (66% vs. 39%, AOR: 2.6, 95% CI: 1.6–4.2), and who had sex with 3+ clients/day than those who had sex with fewer clients (67% vs. 38%, AOR: 3.7, 95% CI:2.5–5.5). Conclusion: FSWs who are older, currently married, practicing sex work for longer duration and with higher clientele were more likely to engage in risky sexual practices. HIV prevention programs should develop strategies to reach these most-at risk group of FSWs to optimize the effectiveness of such programs. [ABSTRACT FROM AUTHOR]

Geophysical evidence strongly supports the complete isolation of India and Madagascar (Indo-Madagascar) by ∼100 million years ago, though sparse terrestrial fossil records from these regions prior to ∼70 million years ago have limited insights into their biogeographic history during the Cretaceous. A new theropod dinosaur, Dahalokely tokana, from Turonian-aged (∼90 million years old) strata of northernmost Madagascar is represented by a partial axial column. Autapomorphies include a prominently convex prezygoepipophyseal lamina on cervical vertebrae and a divided infraprezygapophyseal fossa through the mid-dorsal region, among others. Phylogenetic analysis definitively recovers the species as an abelisauroid theropod and weakly as a noasaurid. Dahalokely is the only known dinosaur from the interval during which Indo-Madagascar likely existed as a distinct landmass, but more complete material is needed to evaluate whether or not it is more closely related to later abelisauroids of Indo-Madagascar or those known elsewhere in Gondwana. [ABSTRACT FROM AUTHOR]

New Delhi metallo-β-lactamase (NDM-1) is a new metallo-β-lactamase (MBL) that has recently emerged as a global threat because it confers bacteria with resistance to almost all clinically used β-lactam antibiotics. To determine the molecular basis of this threat, NDM-1 was purified from Escherichia coli TransB (DE3) carrying cloned blaNDM-1 gene by an anion-exchange chromatography step followed by a gel permeation chromatography step. The purified enzyme was stable even in extremely alkaline buffer (pH 11) and reached its highest activity at a low temperature (15°C), which was different from other MBLs. The 50% inhibition concentration of EDTA against NDM-1 was 412 nM, which showed that NDM-1 was more susceptible to EDTA than other MBLs. The effects of zinc on NDM-1 differed between cephem and carbapenem complexes, but inhibition at high Zn2+ concentration was observed for all of tested β-lactam compounds. [ABSTRACT FROM AUTHOR]

Non-polio enteroviruses (NPEVs) have been reported frequently in association with acute flaccid paralysis (AFP) cases during Polio Surveillance Programs (PSPs) worldwide. However, there is limited understanding on the attributes of their infections. This study reports characteristics of NPEVs isolated from AFP cases, investigated during PSPs held in 2009–2010, in Karnataka and Kerala states of south-western India having varied climatic conditions. NPEV cell culture isolates derived from stool specimens that were collected from 422 of 2186 AFP cases (<1–14 years age) and 17 of 41 asymptomatic contacts; and details of all AFP cases/contacts were obtained from National Polio Laboratory, Bangalore. The distribution of NPEV infections among AFP cases and circulation pattern of NPEV strains were determined by statistical analysis of the data. Genotyping of all NPEV isolates was carried out by partial VP1 gene sequencing and phylogenetic analysis. NPEV positive AFP cases were significantly higher in children aged <2 years; with residual paralysis; in summer months; and in regions with relatively hot climate. Genotyping of NPEVs identified predominance of human enteroviruses (HEV)-B species [81.9%—Echoviruses (E): 57.3%; coxsackieviruses (CV) B: 15%; numbered EVs: 8.9%; CVA9: 0.7%] and low levels of HEV-A [14.5%—CVA: 6%; numbered EVs: 8.5%] and HEV-C [3.6%—CVA: 2.6%; numbered EVs: 1%] species, encompassing 63 genotypes. EV76 (6.3%) and each of E3, CVB3 and E9 (4.97%) were found frequently during 2009 while E11 (6.7%), CVB1 (6.1%), E7 (5.1%) and E20 (5.1%) were detected commonly in 2010. A marked proportion of AFP cases from children aged <2 years; presenting with fever; and from north and south interior parts of Karnataka state was detected with E/numbered EVs than that found with CVA/CVB. This study highlights the extensive genetic diversity and diverse circulation patterns of NPEV strains in AFP cases from different populations and climatic conditions. [ABSTRACT FROM AUTHOR]

A total of 874 fecal specimens (446 diarrheal cases and 428 controls) from diarrheal children admitted in the Infectious Diseases Hospital, Kolkata and age and sex matched asymptomatic subjects from an urban community were assessed for the prevalence of enterotoxigenic Bacteroides fragilis (ETBF). Isolates of B. fragilis were tested for the presence of enterotoxin gene (bft) by PCR. The detection rate of ETBF was 7.2% (63 of 874 specimens) that prevailed equally in diarrheal cases and controls (7.2% each; 32 of 446 cases and 31 of 428 controls). Male children up to one year age group was significantly (p<0.05) associated with ETBF infection as compared to children > 2 years of age in cases and controls. In 25 ETBF isolates, the bft gene was genotyped using PCR-RFLP and only two alleles were identified with prevalence rate of 40% and 60% for bft-1 and bft-3, respectively. All the ETBF isolates were susceptible for chloramphenicol and imipenem but resistant to clindamycin (48%), moxifloxacin (44%) and metronidazole (32%). Resistance of ETBF to moxifloxacin (44%) and metronidazole is an emerging trend. Pulsed-field gel electrophoresis (PFGE) revealed that majority of the ETBF isolates are genetically diverse. In the dendrogram analysis, two clusters were identified, one with ETBF resistant to 5–8 antimicrobials and the other cluster with metronidazole and moxifloxacin susceptible isolates from diarrheal cases. To our knowledge, this is the first detailed report on ETBF from India indicating its clinical importance and molecular characteristics. [ABSTRACT FROM AUTHOR]

We attempt to evaluate the nature of association of TCF7L2 gene variants with T2DM, for the first time in the population of Hyderabad, which is considered to be diabetic capital of India. It is a case-control study of the three SNPs of TCF7L2, rs7903146, rs12255372 and rs11196205, genotyped on Sequenom Massarray platform, in a sample of 758 patients and 621 controls. The risk allele frequency of the three SNPs was found to be significantly higher in the T2DM cases than controls, implicating susceptibility for diabetes (p<0.01). The greatest risk of developing the disease was conferred by rs7903146. Further, the logistic regression of genotypes of each SNP under log additive model, and the haplotypes constituted by at least one of the three risk alleles also show significantly greater risk of developing T2DM when compared to the wild type haplotype. Further, BMI and WHR emerge as significant covariates with confounding effects. The strong association of the TCF7L2 SNPs with T2DM is consistent with the findings among other Indian and Non-Indian populations, suggesting universal phenomena of its association across ethnic groups globally, both within and outside the Indian subcontinent, albeit the functional relevance of these SNPs needs yet to be established. [ABSTRACT FROM AUTHOR]

Toothed whales (Cetacea, odontoceti) use biosonar to navigate their environment and to find and catch prey. All studied toothed whale species have evolved highly directional, high-amplitude ultrasonic clicks suited for long-range echolocation of prey in open water. Little is known about the biosonar signals of toothed whale species inhabiting freshwater habitats such as endangered river dolphins. To address the evolutionary pressures shaping the echolocation signal parameters of non-marine toothed whales, we investigated the biosonar source parameters of Ganges river dolphins (Platanista gangetica gangetica) and Irrawaddy dolphins (Orcaella brevirostris) within the river systems of the Sundarban mangrove forest. Both Ganges and Irrawaddy dolphins produced echolocation clicks with a high repetition rate and low source level compared to marine species. Irrawaddy dolphins, inhabiting coastal and riverine habitats, produced a mean source level of 195 dB (max 203 dB) re 1 µPapp whereas Ganges river dolphins, living exclusively upriver, produced a mean source level of 184 dB (max 191) re 1 µPapp. These source levels are 1–2 orders of magnitude lower than those of similar sized marine delphinids and may reflect an adaptation to a shallow, acoustically complex freshwater habitat with high reverberation and acoustic clutter. The centroid frequency of Ganges river dolphin clicks are an octave lower than predicted from scaling, but with an estimated beamwidth comparable to that of porpoises. The unique bony maxillary crests found in the Platanista forehead may help achieve a higher directionality than expected using clicks nearly an octave lower than similar sized odontocetes. [ABSTRACT FROM AUTHOR]

Major dengue epidemics have been observed in the Indian subcontinent since the 1980s and have occurred with increased hospitalizations and mortality. In 2011, the first major epidemic of dengue occurred in Lahore, the second largest city in Pakistan, and resulted in 21,685 confirmed cases and 350 deaths. To investigate the possible viral causes for the increased epidemic activity, we determined the predominant serotype and characterized the viruses genetically. Of 50 patients carefully selected as probable dengue fever or dengue hemorrhagic fever, 34 were positive by virologic testing (i.e. PCR and/or virus isolation). DENV-2 was detected in 32 patients and DENV-1 in two. A total of 24 partial and three full DENV genomes were sequenced. Phylogenetic analyses of the capsid (C), pre-membrane (prM), and envelope genes comprising 2500 nucleotides in length indicated that all DENV-2 isolates in Pakistan since 2007 form a monophyletic lineage that is endemic in the country. These viruses were all of the cosmopolitan genotype (IV) and most closely related to viruses isolated in India and Sri Lanka in the past two decades. Phylogenetic analyses of data currently available in GenBank suggest that the Cosmopolitan genotype has diverged into two geographically distinct sub-lineages: sub-lineage IV-a has only been observed in Southeast Asia, China and Oceania, while IV-b is prevalent in the Indian subcontinent. These results highlight the increased diversity of dengue viruses as they spread geographically within the region. [ABSTRACT FROM AUTHOR]

Background: National policy in India recommends HIV testing of all patients with TB. In West Bengal state, only 28% of patients with TB were tested for HIV between April-June, 2010. We conducted a cross-sectional survey to understand patient, provider and health system related factors associated with low uptake of HIV testing among patients with TB. Methods: We reviewed TB and HIV program records to assess the HIV testing status of patients registered for anti-TB treatment from July-September 2010 in South-24-Parganas district, West Bengal, assessed availability of HIV testing kits and interviewed a random sample of patients with TB and providers. Results: Among 1633 patients with TB with unknown HIV status at the time of diagnosis, 435 (26%) were tested for HIV within the intensive phase of TB treatment. Patients diagnosed with and treated for TB at facilities with co-located HIV testing services were more likely to get tested for HIV than at facilities without [RR = 1.27, (95% CI 1.20–3.35)]. Among 169 patients interviewed, 67 reported they were referred for HIV testing, among whom 47 were tested. During interviews, providers attributed the low proportion of patients with TB being referred and tested for HIV to inadequate knowledge among providers about the national policy, belief that patients will not test for HIV even if they are referred, shortage of HIV testing kits, and inadequate supervision by both programs. Discussion: In West Bengal, poor uptake of HIV testing among patients with TB was associated with absence of HIV testing services at sites providing TB care services and to poor referral practices among providers. Comprehensive strategies to change providers’ beliefs and practices, decentralization of HIV testing to all TB care centers, and improved HIV test kit supply chain management may increase the proportion of patients with TB who are tested for HIV. [ABSTRACT FROM AUTHOR]

Edenopteron keithcrooki gen. et sp. nov. is described from the Famennian Worange Point Formation; the holotype is amongst the largest tristichopterids and sarcopterygians documented by semi-articulated remains from the Devonian Period. The new taxon has dentary fangs and premaxillary tusks, features assumed to be derived for large Northern Hemisphere tristichopterids (Eusthenodon, Hyneria, Langlieria). It resembles Eusthenodon in ornament, but is distinguished by longer proportions of the parietal compared to the post-parietal shield, and numerous differences in shape and proportions of other bones. Several characters (accessory vomers in the palate, submandibulars overlapping ventral jaw margin, scales ornamented with widely-spaced deep grooves) are recorded only in tristichopterids from East Gondwana (Australia-Antarctica). On this evidence Edenopteron gen. nov. is placed in an endemic Gondwanan subfamily Mandageriinae within the Tristichopteridae; it differs from the nominal genotype Mandageria in its larger size, less pointed skull, shape of the orbits and other skull characters. The hypothesis that tristichopterids evolved in Laurussia and later dispersed into Gondwana, and a derived subgroup of large Late Devonian genera dispersed from Gondwana, is inconsistent with the evidence of the new taxon. Using oldest fossil and most primitive clade criteria the most recent phylogeny resolves South China and Gondwana as areas of origin for all tetrapodomorphs. The immediate outgroup to tristichopterids remains unresolved – either Spodichthys from Greenland as recently proposed, or Marsdenichthys from Gondwana, earlier suggested to be the sister group to all tristichopterids. Both taxa combine two characters that do not co-occur in other tetrapodomorphs (extratemporal bone in the skull; non-cosmoid round scales with an internal boss). Recently both ‘primitive’ and ‘derived’ tristichopterids have been discovered in the late Middle Devonian of both hemispheres, implying extensive ghost lineages within the group. Resolving their phylogeny and biogeography will depend on a comprehensive new phylogenetic analysis. [ABSTRACT FROM AUTHOR]

Background: Increase in the number of multidrug resistant pathogens and the accompanied rise in case fatality rates has hampered the treatment of many infectious diseases including cholera. Unraveling the mechanisms responsible for multidrug resistance in the clinical isolates of Vibrio cholerae would help in understanding evolution of these pathogenic bacteria and their epidemic potential. This study was carried out to identify genetic factors responsible for multiple drug resistance in clinical isolates of Vibrio cholerae O1, serotype Ogawa, biotype El Tor isolated from the patients admitted to the Infectious Diseases Hospital, Kolkata, India, in 2009. Methodology/Principal Findings: One hundred and nineteen clinical isolates of V. cholerae were analysed for their antibiotic resistance phenotypes. Antibiogram analysis revealed that majority of the isolates showed resistance to co-trimoxazole, nalidixic acid, polymixin B and streptomycin. In PCR, SXT integrase was detected in 117 isolates and its sequence showed 99% identity notably to ICEVchInd5 from Sevagram, India, ICEVchBan5 from Bangladesh and VC1786ICE sequence from Haiti outbreak among others. Antibiotic resistance traits corresponding to SXT element were transferred from the parent Vibrio isolate to the recipient E. coli XL-1 Blue cells during conjugation. Double-mismatch-amplification mutation assay (DMAMA) revealed the presence of Haitian type ctxB allele of genotype 7 in 55 isolates and the classical ctxB allele of genotype 1 in 59 isolates. Analysis of topoisomerase sequences revealed the presence of mutation Ser83 → Ile in gyrA and Ser85→ Leu in parC. This clearly showed the circulation of SXT-containing V. cholerae as causative agent for cholera in Kolkata. Conclusions: There was predominance of SXT element in these clinical isolates from Kolkata region which also accounted for their antibiotic resistance phenotype typical of this element. DMAMA PCR showed them to be a mixture of isolates with different ctxB alleles like classical, El Tor and Haitian variants. [ABSTRACT FROM AUTHOR]

Background: Influenza A virus is one of world’s major uncontrolled pathogen, causing seasonal epidemic as well as global pandemic. This was evidenced by recent emergence and continued prevalent 2009 swine origin pandemic H1N1 Influenza A virus, provoking first true pandemic in the past 40 years. In the course of its evolution, the virus acquired many mutations and multiple unidentified molecular determinants are likely responsible for the ability of the 2009 H1N1 virus to cause increased disease severity in humans. Availability of limited data on complete genome hampers the continuous monitoring of this type of events. Outbreaks with considerable morbidity and mortality have been reported from all parts of the country. Methods/Results: Considering a large number of clinical cases of infection complete genome based sequence characterization of Indian H1N1pdm virus and their phylogenetic analysis with respect to circulating global viruses was undertaken, to reveal the phylodynamic pattern of H1N1pdm virus in India from 2009–2011. The Clade VII was observed as a major circulating clade in phylogenetic analysis. Selection pressure analysis revealed 18 positively selected sites in major surface proteins of H1N1pdm virus. Conclusions: This study clearly revealed that clade VII has been identified as recent circulating clade in India as well globally. Few clade VII specific well identified markers undergone positive selection during virus evolution. Continuous monitoring of the H1N1pdm virus is warranted to track of the virus evolution and further transmission. This study will serve as a baseline data for future surveillance and also for development of suitable therapeutics. [ABSTRACT FROM AUTHOR]

Background: Known as ‘neglected disease’ because relatively little effort has been applied to finding cures, leishmaniasis kills more than 150,000 people every year and debilitates millions more. Visceral leishmaniasis (VL), also called Kala Azar (KA) or black fever in India, claims around 20,000 lives every year. Whole genome analysis presents an excellent means to identify new targets for drugs, vaccine and diagnostics development, and also provide an avenue into the biological basis of parasite virulence in the L. donovani complex prevalent in India. Methodology/Principal Findings: In our presently described study, the next generation SOLiD™ platform was successfully utilized for the first time to carry out whole genome sequencing of L. donovani clinical isolates from India. We report the exceptional occurrence of insect trypanosomatids in clinical cases of visceral leishmaniasis (Kala Azar) patients in India. We confirm with whole genome sequencing analysis data that isolates which were sequenced from Kala Azar (visceral leishmaniasis) cases were genetically related to Leptomonas. The co-infection in splenic aspirate of these patients with a species of Leptomonas and how likely is it that the infection might be pathogenic, are key questions which need to be investigated. We discuss our results in the context of some important probable hypothesis in this article. Conclusions/Significance: Our intriguing results of unusual cases of Kala Azar found to be most similar to Leptomonas species put forth important clinical implications for the treatment of Kala Azar in India. Leptomonas have been shown to be highly susceptible to several standard leishmaniacides in vitro. There is very little divergence among these two species viz. Leishmania sp. and L. seymouri, in terms of genomic sequence and organization. A more extensive perception of the phenomenon of co-infection needs to be addressed from molecular pathogenesis and eco-epidemiological standpoint. [ABSTRACT FROM AUTHOR]