Chronic obstructive pulmonary disease (COPD) affect millions of people worldwide and is known to be one of the leading causes of death. The highly sensitive airways protect themselves from irritants by cough and sneeze which propel endogenous and exogenous substances to minimize airway noxious effects. One noxious effect of these substances is activation of peripheral sensory nerve endings of nociceptor neurons innervating these airways lining thus transmitting dangerous signals from the environment to the central nervous system (CNS). Nociceptor neurons include transient receptor potential (TRP) ion channels, especially the vanilloid and ankyrin subfamilies, TRPV1/A1 which can be activated by noxious chemical challenges in models of airways disease. As oxidative stress may activate airways sensory neurons and contribute to COPD exacerbations we sought to review the role that TRP channel activation by oxidative signals may have on airway responses. i0 t would be prudent to target the TRP channels with antagonists and lower systemic oxidative stress with agents that can modulate TRP expression and boost the endogenous levels of antioxidants for treatment and management of COPD.

The role of low grade systemic inflammation as evidenced by elevated high sensitivity C-reactive protein (hsCRP) levels in the pathogenesis of atherosclerotic vascular disease has been intensely investigated through observational studies and clinical trials in the past two decades. On the basis of evidence that has accrued, hsCRP measurement has been integrated into the Reynolds risk scoring system to predict cardiovascular risk. The JUPITER trial proved the benefit of statins in cardiovascular risk reduction in patients with low grades of systemic inflammation and 'normal' cholesterol levels. However, substantial evidence has been generated from western studies. We, therefore, conducted a scoping review for studies done in India with a view to identify gaps in evidence and make further recommendations. Most Indian studies had small sample sizes and short term follow ups. There were no large population based prospective studies where patients were followed up for long periods of time for major cardiovascular end points. An analysis of the hsCRP level from the control arms of case-control studies derived a mean hsCRP value of 1.88 mg/l, which is higher than the western population where values < 1 mg/l are classified as low cardiovascular risk. Further large prospective cohort studies with longer term follow ups are essential before we can make further recommendations to integrate hsCRP into risk prediction models for cardiovascular disease prevention.

Background & objectives: No clear therapeutic benefits of antipsychotics have been reported for the treatment of behavioural symptoms in autism. This systematic review provides an assessment of evidence for treating irritability in autism by aripiprazole. Methods: The databases of MEDLINE/PubMed and Google Scholar were searched for relevant articles about the effect of aripiprazole in children with autism. The articles were searched according to the inclusion and exclusion criteria specifed for this review. All the double-blind, controlled, randomized, clinical trials examining the efficacy of aripiprazole for treating children and adolescents with autism were included. Results: From the 93 titles identified, 26 were irrelevant and 58 were evaluated for more details. Only five articles met the inclusive criteria. The evidence from precise randomized double blind clinical trials of aripiprazole for the treatment of autism in children and adolescents was convincing enough to recommend aripiprazole. Adverse effects were not very common and were usually mild. Interpretation & conclusions: Current evidence suggests that aripiprazole is as effective and safe as risperidone for treating irritability in autism. However, further studies with larger sample size and longer duration are required.

Background & objectives: The Vitamin-D receptor (VDR) regulates vitamin D levels and calcium metabolism in the body and these are known to be associated with endocrine dysfunctions, insulin resistance and type-2 diabetes in polycystic ovarian syndrome (PCOS). Studies on VDR polymorphisms among PCOS women are sparse. We undertook this study to investigate the association pattern of VDR polymorphisms (Cdx2, Fok1, Apa1 and Taq1) with PCOS among Indian women. Methods: For the present study, 250 women with PCOS and 250 normal healthy control women were selected from Hyderabad city, Telangana, India. The four VDR polymorphisms were genotyped and analysed using ASM-PCR (allele specific multiple PCR) and PCR-RFLP (restriction fragment length polymorphism). Results: The genotype and allele frequency distributions of only Cdx2 showed significant difference between the PCOS cases and control women, indicating protective role of this SNP against PCOS phenotype. However, significant association was observed between VDR genotypes and some of the PCOS specific clinical/biochemical traits. For example, Fok1 showed a significant genotypic difference for the presence of infertility and Cdx2 genotpes showed association with testosterone levels. Further, the two haplotypes, ACCA and ACTA, were found to be significantly associated with PCOS indicating haplotype specific risk. Interpretation & conclusions: Although VDR polymorphisms have not shown significant association with PCOS, in view of functional significance of the SNPs considered, one cannot yet rule out the possibility of their association with PCOS. Further, specifically designed studies on large cohorts are required to conclusively establish the role of VDR polymorphisms in PCOS, particularly including data on vitamin D levels.

Background & objectives: Streptococcus pneumoniae is a major cause of morbidity and mortality especially in children less than five years, particularly in India. We present data on S.pneumoniae infections in children less than five years age group, with response to its serotype distribution, antibiotic resistance profile and available vaccines expected coverage. Methods: Children aged less than five, who were suspected for invasive pneumococcal disease were included in the study and their sterile body fluids were investigated for the presence of S. pneumoniae. Invasive S. pneumoniae isolates from sterile body fluids were identified by bile solubility and optochin susceptibility test. Pneumococcal serotyping was performed with co-agglutination technique and reconfirmed with multiplex PCR. Results: The most common pneumococcal serotypes causing invasive infections in children less than five years of age were 14, 19F, 5, 6A and 6B. Of the 114 S. pneumoniae isolates studied, 110 (96.4%) were non-susceptible to co-trimoxazole and 30 per cent were non-susceptible to erythromycin, 5.2 per cent of the isolates were non-susceptible to penicillin and only 0.8 per cent was non-susceptible to cefotaxime. Interpretation & conclusions: Our results indicate that PCV-10 can protect against 64 per cent of serotypes causing invasive pneumococcal infections. Use of PCV-13 in this region can provide increase in protection upto 74.6 per cent against serotypes causing invasive pneumococcal infections. Incorporating PCV-13 in the Universal Immunization Programme may provide incremental protection against IPD serotypes in the southern region of the country.

Background & objectives: Elevated blood pressure (BP) in the young predicts serious cardiovascular events in the adults. High prevalence of adult hypertension reported from Assam, North East (NE) India may be linked with elevated blood pressure in the childhood. The present study was an attempt to describe the distribution of BP and correlates of hypertension in children aged 5-14 yr. Methods: A total of 10,003 school children from 99 schools of Dibrugarh district, Assam, NE India, were surveyed by stratified random cluster method. Blood pressure, demographic and anthropometric information were recorded. Blood pressure was categorized in to normal, prehypertension, stage I and stage II hypertension. Results: Girls had significantly higher (104.2 ± 12.0 vs. 103.2 ± 11.6 mm Hg, p0 <0.001) mean systolic blood pressure (SBP) than boys. Both SBP and diastolic blood pressure (DBP) revealed significant correlation with age, height, weight and BMI in overall and in gender specific analysis. Hypertension was found in 7.6 per cent school children (Boys: 7.3%, Girls: 7.8%). In multivariable analysis older age (OR 3.3, 95% CI: 2.82-3.91), children from tea garden community (OR 1.3, 95% CI: 1.08-1.55) and other community (OR 1.4, 95% CI: 1.18-1.73) and overweight (OR 1.5, 95% CI: 1.1-2.1) were independently associated with hypertension. Interpretation & conclusions:Mean blood pressure in the young school children of 5-14 yr was high. A programme comprising screening, early detection and health promotion through school health programmes may help prevent future complications of hypertension.

Background & objectives: Failure to adhere to anti-retroviral therapy (ART) can lead to a range of unfavourable consequences impacting upon people living with HIV (PLH) and society. It is, therefore, paramount that ART adherence is measured in a reliable manner and factors associated with adherence are identified. Lack of such data from West Bengal necessitated undertaking the current study. Methods: Participants were included during August-October, 2011 from three Drop-In-Centres (DICs) from the three districts of West Bengal, India. ART-adherence was calculated by using formula based on pill-count and records collected from ART-card in possession of each of the 128 consenting adult PLH. Information on self-reported adherence, socio-demography, and adherence influencing issues was also collected through interviewer-administered questionnaire. Results: Of the 128 PLH, 99 (77%) and 93 (73%) PLH had ≥90 per cent and ≥95 per cent adherence, respectively to ART. Conversely, subjective reporting captured much higher proportion of PLH as 'well adherent'; a finding having implications for ongoing ART programme. Factors, independently associated with poor adherence (<90%), were '7 ^th to 12 ^th month period of ART intake' (adjusted OR=9.5; 90% CI 1.9 - 47.3; p0 =0.02) and 'non-disclosure of HIV status to family members' (adjusted OR=4; 90% CI 1.3 - 13; P=0.05. Results at 95 per cent adherence cut-off were similar. Interpretation & conclusions: Enabling environment, which would encourage people to disclose their HIV status and in turn seek adherence partners from families and beyond and ongoing adherence-counselling appear to be important issues in the programme. Relevance of these study findings in wider context is conceivable.

Background & objectives: Injecting drug use is a major route of hepatitis C virus (HCV) infection in India, but there may be other risk factors also. This study was carried out to determine the seroprevalence of anti-HCV antibody in injecting drug users (IDUs) vs. non-IDUs (NIDUs), and to study the risk estimates for HCV seropositivity in the total sample of substance users with regard to various demographic, clinical, behavioural and personality factors. Methods: The IDUs (n = 201) and NIDUs (n = 219) were assessed for demographic, clinical and behavioural information, and were rated on instruments for severity of dependence, risk behaviour and personality profiles. Anti-HCV antibody was tested by ELISA and confirmed by recombinant immunoblot assay (RIBA) test. Results: Almost one-third of the IDUs (64 of 201; 31.8%) were positive for anti-HCV antibody, as opposed to only seven (3.2%) of the NIDUs. The four risk factors strongly associated with HCV positivity in multivariate analysis were sharing syringe [Exp(B) 75.04; 95%CI 18.28-307.96; P<0.001], reuse of injection accessories (16.39; 3.51-76.92; P<0.001), blood transfusion (5.88; 1.63-21.23; P=0.007) and IDU status (3.60; 1.26-10.31; P=0.017). Other variables less strongly but significantly associated with HCV positivity were multiple sex partners, opioid dependence, risk behaviour scores, impulsivity, and lower age of onset of drug use. Interpretation & conclusions: Our study showed a high seroprevalence of anti-HCV antibody in IDUs. In the substance users, HCV positivity was significantly and independently associated with several clinical, behavioural, and personality risk factors.

Background & objectives: Hepatitis B virus (HBV), human immunodeficiency virus (HIV), hepatitis C virus (HCV) and syphilis infections pose a great threat to blood safety. This study was undertaken to investigate the seroprevalence of serologic markers for transfusion transmitted infections (TTIs) among blood donors at a hospital based blood centre in north India over a period of nine years. Methods: The results of serologic markers for TTIs (HBsAg, anti-HCV, anti-HIV and syphilis) of all blood donations (both voluntary and replacement) at our hospital from January 2005 to December 2013 were screened. Additional analysis was conducted to examine the prevalence trends associated with each of the positive marker. Results: The data of 180,477 donors [173,019 (95.86%) males and 7,458 (4.13%) females] were analyzed. Replacement donations [174,939 (96.93%)] represented the majority whereas, only 5,538 (3.06%) donations were from the voluntary donors. The risk of blood being reactive was three times higher in male donors when compared with the female donors. The risk of blood being reactive for one or more infectious markers was 2.1 times higher in replacement donors when compared with the voluntary donors. Seropositivity of HIV, HBsAg, HBcAb, syphilis showed a significant decreasing trend (P<0.05) while there was an increasing trend in HCV infection which was insignificant. Interpretation & conclusions: This study reflects that the risk of TTIs has been decreased over time with respect to HIV, HBV and syphilis, but the trends for HCV remains almost the same in blood donors. Blood transfusion remains a risk factor for the spread of blood-borne infections. Therefore, improvements are needed to strengthen both safety and availability of blood.

Background & objectives: Studies have shown the bactericidal potential of econazole and clotrimazole against Mycobacterium tuberculosis under in vitro and ex vivo conditions along with their synergism with conventional antituberculosis drugs. These molecules were also found to be effective against different multidrug resistant (MDR) M. tuberculosis isolates in vitro. Hence the present study was designed to evaluate the in vivo antimycobacterial potential of moxifloxacin and econazole alone and in combination against multidrug resistant tuberculosis (MDR-TB) in a mice model. Methods: Mice were infected with 2.5×10 ^[7] bacilli of MDR strain of M. tuberculosis by aerosol route of infection. After four weeks of infection, chemotherapy was started orally by moxifloxacin 8.0 mg/kg body wt and econazole 3.3 mg/kg alone and in combination, as well as with four first line anti-tuberculosis drugs as a positive control. The animals were sacrificed and the lungs and spleen were excised under aspetic conditions. The tissues were homogenized with sterile normal saline, an aliquot of the homogenate was plated on Middlebrook 7H11 agar supplemented with oleate albumin dextrose catalase (OADC) and incubated at 37°C for four weeks. The number of visible and individual colonies were counted. Results: The first line anti-tuberculosis drugs (RIF+INH+EMB+PZA) after eight weeks of therapy had no impact as the bacillary load in lungs and spleens remained unchanged. However, econazole, moxifloxacin alone as well as in combination significantly reduced the bacillary load in lungs as well as in spleens of MDR-TB bacilli infected mice. Interpretation & conclusions: Co-administration of the two drugs (econazole and moxifloxacin) to MDR-TB strain JAL-7782 infected mice exhibited additive effect, the efficacy of the drugs in combination being higher as compared with ECZ or MOX alone. These results were substantiated by histopathological studies. This study suggests the utility of econazole for the treatment of MDR tuberculosis and warrants further work in this direction.

Background & objectives: The two major genotypic markers that distinguish community acquired (CA) from hospital acquired (HA) methicillin resistant Staphylococcus aureus (MRSA) isolates are the architecture of mobile genetic element (SCCmec type) and presence of panton valentine leukocidin (PVL) toxin. This study was conducted to determine the molecular characteristics of CA- and HA- MRSA and methicillin sensitive S. aureus (MSSA) isolates in Sikkim. Methods: A total of 150 clinical isolates of S. aureus isolated from various clinical specimens were subjected to duplex (mec-A and pvl gene) and multiplex (SCCmec typing) PCR. Results: Of the 150 isolates, 53 (35.33%) and 66 (44%) were positive for mec-A (MRSA) and pvl genes, respectively. Thirty eight (25.33%) met the definition of CA-MRSA and 15 (10%) of HA-MRSA and the remaining 63 (42%) and 34 (22.66%) as CA- and HA-MSSA, respectively. No significant difference was seen in the distribution of PVL toxin in MRSA and MSSA isolates, but it was significantly (P<0.001) high in overall MRSA isolates than in MSSA. The majority of the MRSA isolates showed a double amplification band of SCCmec type III plus V (54.71%), and only a fewer isolates were amplified by single DNA fragments of type I (1.88%), III (3.77%), IVa (1.88%) and V (11.32%). SCCmec types I, III, IVa, were found only in HA-MRSA isolates, whereas type V in both the CA- and HA-MRSA. AST pattern showed that 18.42 per cent (7/38) and 46.66 per cent (7/15) were multidrug resistant (MDR)-CA-MRSA and MDR-HA-MRSA, respectively. Interpretation & conclusions: The present results show that SCCmec type V MRSA has been on the rise, and genotypic markers such as pvl gene detection used for the differentiation of these clinically distinct isolates of MRSA may not be reliable.

Background & objectives: Carbapenem resistance mediated by carbapenemases is increasingly being reported worldwide. This study was conducted to know the occurrence of important carbapenem resistance encoding genes in Gram-negative bacilli (GNB) causing complicated urinary tract infection (CUTI), and to look at the genetic diversity of these isolates. Methods: The study was carried out on 166 consecutive carbapenem resistant uropathogens (CRU) isolated from cases with CUTI during 2008 and 2012. Carbapenemase production was characterized phenotypically and polymerase chain reaction was used to detect bla _VIM , bla _IMP , bla _KPC , and bla _NDM-1 . BOX- PCR was done on 80 randomly selected isolates for molecular typing. Results: The bla _VIM gene was present in 34 (43.6%), bla _IMP in five (6.4%) and none of the isolates from 2008 had bla _NDM-1 or bla _KPC genes. Among the isolates from 2012, bla _NDM-1 gene was present in 47 (53.4%), bla _VIM in 19 (24.4%), bla _IMP in one (1.1%) and none had bla _KPC . There were nine isolates during the two years which had multiple genes encoding carbapenemases; while 66 did not have any of the genes tested. Of the 80 isolates subjected to BOX-PCR, 58 could be used for analysis and showed, presence of multiple clusters of carbapenem resistant isolates and absence of a single dominant clone. Interpretation & conclusions: The bla _NDM-1 gene was absent in our isolates obtained during 2008 but was present amongst Enterobacteriaceae isolated in 2012. The bla _KPC gene was also not found. Nine isolates obtained during the two years had multiple genes encoding carbapenemases confirming the previous reports of emergence of GNB containing genes encoding multiple carbapenemases. Typing using BOX-PCR indicated that this emergence was not because of clonal expansion of a single strain, and multiple strains were circulating at a single point of time.