Down syndrome (DS) is one of the most common chromosomal disorders, occurring in one out of 700-1000 live births, and the most common cause of mental retardation. Thyroid dysfunction is the most typical endocrine abnormality in patients with DS. It is well known that thyroid dysfunction is highly prevalent in children and adults with DS and that both hypothyroidism and hyperthyroidism are more common in patients with DS than in the general population. Increasing evidence has shown that DS individuals are under unusual increased oxidative stress, which may be involved in the higher prevalence and severity of a number of pathologies associated with the syndrome, as well as the accelerated ageing observed in these individuals. The gene for Cu/Zn superoxide dismutase (SOD1) is coded on chromosome 21 and it is overexpressed (~50%) resulting in an increase of reactive oxygen species (ROS) due to overproduction of hydrogen peroxide (H ₂ O ₂ ). ROS leads to oxidative damage of DNA, proteins and lipids, therefore, oxidative stress may play an important role in the pathogenesis of DS.

Background & objectives: Information available on drug consumption is inadequate in most low and middle income countries. This systematic review was conducted to analyse published work on drug utilization research/studies (DUR) in the SEARO region of WHO for study objectives, methodology, results and recommendations and to identify the need for improving DUR and the use of the ATC/DDD system. Methods: A literature search for DUR was carried out in biomedical databases (PubMed, Scirus, Scopus and Google Scholar) up to May 2012. Publications were selected if those were in the English language, describing DUR or prescription practices, and study conducted in the WHO-SEARO countries. Results: A total of 318 publications were included in the review. Of these, 67 per cent were from India and 13 per cent were from Thailand. Majority of the publications were hospital based; only 16 per cent were community based. The ATC/DDD system was used in only 20 per cent of the publications, of which 73 per cent publications used DDD indicators. Several publications focused on antibiotics (31%). Publications that recommended the need for a policy or intervention to improve prescription practices/rational drug use amounted to 35 per cent. Interpretation & conclusions: Drug utilization studies using ATC/DDD system need to be promoted and carried out on an ongoing basis. DUR is important for rational use of drugs. Its relevance to policy making and resource allocation needs to be emphasized.

A survey was conducted to ascertain practice of antimicrobial stewardship programme (AMSP) in India for 2013. A total of 20 health care institutions (HCI) responded to a detailed questionnaire. All the institutions contacted were tertiary care HCI, of which 12 were funded by government (GHCI) and 8 were corporate/private HCI (PHCI). Further, all catered to both rural and urban populations and were spread across the country. Written documents were available with 40 per cent for AMSP, 75 per cent for hospital infection control (HIC) and HIC guidelines and 65 per cent for antimicrobial agents (AMA) prescription guidelines. Records were maintained for health care associated infections (HCAI) by 60 per cent HCI. Antimicrobial resistance (AMR) data were being analysed by 80 per cent HCI. AMA usage data were analysed by only 25 per cent HCI and AMA prescription audit and feedback by 30 per cent. PHCI performed better than GHCI across all fields of AMSP. The main contributory factor was possibly the much higher level of accreditation of PHCI hospitals and their diagnostic laboratories. The absence of infectious diseases physicians and clinical pharmacists is worrying and demands careful attention.

Background & objectives: Overweight and obesity are rapidly increasing in countries like India. This study was aimed at determining the prevalence of generalized, abdominal and combined obesity in urban and rural India. Methods: Phase I of the ICMR-INDIAB study was conducted in a representative population of three s0 tates [Tamil Nadu (TN), Maharashtra (MH) and Jharkhand (JH)] and one Union Territory (UT)[Chandigarh (CH)] of India. A stratified multi-stage sampling design was adopted and individuals ≥20 yr of age were included. WHO Asia Pacific guidelines were used to define overweight [body mass index (BMI) ≥23 kg/m ^[2] but <25 kg/m ^[2]], generalized obesity (GO, BMI≥25kg/m ^[2] , abdominal obesity (AO, waist circumference ≥90 cm for men and ≥80cm for women) and combined obesity (CO, GO plus AO). Of the 14,277 participants, 13,800 subjects (response rate, 96.7%) were included for the analysis (urban: n=4,063; rural: n=9737). Results: The prevalence of GO was 24.6, 16.6, 11.8 and 31.3 per cent among residents of TN, MH, JH and CH, while the prevalence of AO was 26.6, 18.7, 16.9 and 36.1 per cent, respectively. CO was present in 19.3, 13.0, 9.8 and 26.6 per cent of the TN, MH, JH and CH population. The prevalence of GO, AO and CO were significantly higher among urban residents compared to rural residents in all the four regions studied. The prevalence of overweight was 15.2, 11.3, 7.8 and 15.9 per cent among residents of TN, MH, JH and CH, respectively. Multiple logistic regression analysis showed that female gender, hypertension, diabetes, higher socio-economic status, physical inactivity and urban residence were significantly associated with GO, AO and CO in all the four regions studied. Age was significantly associated with AO and CO, but not with GO. Interpretation & conclusions: Prevalence of AO as well as of GO were high in India. Extrapolated to the whole country, 135, 153 and 107 million individuals will have GO, AO and CO, respectively. However, these figures have been estimated from three States and one UT of India and the results may be viewed in this light.

Background & objectives: Despite remarkable progress in airborne, vector-borne and waterborne diseases in India, the morbidity associated with these diseases is still high. Many of these diseases are controllable through awareness and preventive practice. This study was an attempt to evaluate the effectiveness of a preventive care awareness campaign in enhancing knowledge related with airborne, vector-borne and waterborne diseases, carried out in 2011 in three rural communities in India (Pratapgarh and Kanpur-Dehat in Uttar Pradesh and Vaishali in Bihar). Methods: Data for this analysis were collected from two surveys, one done before the campaign and the other after it, each of 300 randomly selected households drawn from a larger sample of Self-Help Groups (SHGs) members invited to join community-based health insurance (CBHI) schemes. Results: The results showed a significant increase both in awareness (34%, p<0.001) and in preventive practices (48%, P=0.001), suggesting that the awareness campaign was effective. However, average practice scores (0.31) were substantially lower than average awareness scores (0.47), even in post-campaign. Awareness and preventive practices were less prevalent in vector-borne diseases than in airborne and waterborne diseases. Education was positively associated with both awareness and practice scores. The awareness scores were positive and significant determinants of the practice scores, both in the pre- and in the post-campaign results. Affiliation to CBHI had significant positive influence on awareness and on practice scores in the post-campaign period. Interpretation & conclusions: The results suggest that well-crafted health educational campaigns can be effective in raising awareness and promoting health-enhancing practices in resource-poor settings. It also confirms that CBHI can serve as a platform to enhance awareness to risks of exposure to airborne, vector-borne and waterborne diseases, and encourage preventive practices.

Background & objectives: Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 Χ 10 ^[8] autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy. Methods: In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI). Results: On intention-to-treat analysis the infusion of MNCs had no positive impact on LVEF improvement of ≥ 5 per cent. The improvement in LVEF after six months was 5.17 ± 8.90 per cent in non SCT group and 4.82 ± 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of ≥ 5 X 10 ^[8] (n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study. Interpretation & conclusions:Infusion of stem cells was found to have no benefit in ST elevation AMI. However, the procedure was safe. A possible benefit was seen when the predefined cell dose was administered which was noted upto three weeks post AMI, but this was not significant and needs confirmation by larger trials.

Background & objectives: Imatinib is the standard first-line treatment for chronic myeloid leukaemia (CML) patients. About 20 to 30 per cent patients develop resistance to imatinib and fail imatinib treatment. One of the mechanisms proposed is varying expression levels of the drug transporters. This study was aimed to determine the expression levels of imatinib transporter genes (OCT1, ABCB1, ABCG2) in CML patients and to correlate these levels with molecular response. Methods: Sixty three CML chronic phase patients who were on 400 mg/day imatinib for more than two years were considered for gene expression analysis study for OCT1, ABCB1 and ABCG2 genes. These were divided into responders and non-responders. The relative transcript expression levels of the three genes were compared between these two categories. The association between the expression values of these three genes was also determined. Results: No significant difference in the expression levels of OCT1, ABCB1 and ABCG2 was found between the two categories. The median transcript expression levels of OCT1, ABCB1 and ABCG2 genes in responders were 26.54, 10.78 and 0.64 versus 33.48, 7.09 and 0.53 in non-responders, respectively. A positive association was observed between the expression of the ABCB1 and ABCG2 transporter genes (r=0.407, P<0.05) while no association was observed between the expression of either of the ABC transporter genes with the OCT1 gene. Interpretation & conclusions: Our findings demonstrated that the mRNA expression levels of imatinib transporter genes were not correlated with molecular response in CML patients. Further studies need to be done on a large sample of CML patients to confirm these findings.

Background & objectives: Inequity in the use of health care services is an important factor affecting the maternal and child survival. In southern Odisha, India, the health indicators remained below compared to the s0 tate and national average. This study identifies various equity issues at individual and community levels that influence women's choice affecting the utilization of maternal health services in a district in southern Odisha. Methods: A qualitative study was carried out in Gajam district, rural region of south Odisha. Ten in-depth interviews were carried out till data saturation with women having less than one year child and 10 focus group discussions with the average eight women in each group having less than five year old child, community and health care providers separately. A total of 120 respondents were included in the study using in-depth interview and focus group discussions. Results: The important determinants in utilization of health care services by women emerging from the study were transportation and financial constraints. In addition, it was found that divergent aetiological concepts and low perceived hospital benefits of the women and community were equally important determinants. Further, community had different perceptions and interpretations of danger signs influencing the risk approach and health care seeking behaviour. Interpretation & conclusions: Our findings show that to increase the utilization of health care services, the grass root health workers should be made aware of specific social determinants of risk, perceptions and preferences. m0 ore attention should be given to the transportation system, and its operational feasibility. The husband of the women and the elders of the family should be considered as an important unit of interjection. A more individualized antenatal consultation could be provided by taking into account women's perception of risk and their explanatory models.

Background & objectives: Amyloid β-peptide (Aβ) has been shown to be responsible for senile plaque formation and cell damage in Alzheimer's disease (AD). This study was aimed to explore the role of natural compound icariin on the aggregation and the cytotoxicity of Aβ in vitro. Methods: Thioflavin T (ThT) fluorescence assay and transmission electron microscopy (TEM) imaging were done to determine the influence of icariin on the aggregation of Aβ_1-42 peptide. MTT assay was used to evaluate the protective effect of icariin on Aβ_1-42 induced cytotoxicity in neuroblastoma SH-SY5Y cells. Results: Icariin inhibited Aβ_1-42 aggregation in a dose-dependent manner. Additionally, icariin also prevented the cytotoxicity of Aβ_1-42 in SH-SY5Y cells by decreasing the production of peroxide hydrogen during the aggregation of this peptide. Interpretation & conclusions: The results indicated a novel antagonistic role of icariin in the neurotoxicity of Aβ_1-42 via inhibiting its aggregation, suggesting that icariin might have potential therapeutic benefits to delay or modify the progression of AD.

Background & objectives: Anthrax caused by Bacillus anthracis is primarily a disease of herbivorous animals, although several mammals are vulnerable to it. ELISA is the most widely accepted serodiagnostic assay for large scale surveillance of cutaneous anthrax. The aims of this study were to develop and evaluate a quantitative ELISA for determination of IgG antibodies against B. anthracis protective antigen (PA) in human cutaneous anthrax cases. Methods: Quantitative ELISA was developed using the recombinant PA for coating and standard reference serum AVR801 for quantification. A total of 116 human test and control serum samples were used in the study. The assay was evaluated for its precision, accuracy and linearity. Results: The minimum detection limit and lower limit of quantification of the assay for anti-PA IgG were 3.2 and 4 µg/ml, respectively. The serum samples collected from the anthrax infected patients were found to have anti-PA IgG concentrations of 5.2 to 166.3 µg/ml. The intra-assay precision per cent CV within an assay and within an operator ranged from 0.99 to 7.4 per cent and 1.7 to 3.9 per cent, respectively. The accuracy of the assay was high with a per cent error of 6.5 - 24.1 per cent. The described assay was found to be linear between the range of 4 to 80 ng/ml (R ^[2] =0.9982; slope=0.9186; intercept = 0.1108). Interpretation & conclusions: The results suggested that the developed assay could be a useful tool for quantification of anti-PA IgG response in human after anthrax infection or vaccination.

Background & objectives: Wolbachia-based vector control strategies have been proposed as a mean to augment the existing measures for controlling dengue vector. Prior to utilizing Wolbachia in novel vector control strategies, it is crucial to understand the Wolbachia-mosquito interactions. Many studies have only focused on the prevalence of Wolbachia in female Aedes albopictus with lack of attention on Wolbachia infection on the male Ae. albopictus which also affects the effective expression of Wolbachia induced- cytoplasmic incompatibility (CI). In this study, field surveys were conducted to screen for the infection status of Wolbachia in female and male Ae. albopictus from various habitats including housing areas, islands and seashore. Methods: Adult Ae. albopictus (n=104) were collected using human landing catches and hand aspirator. Standard ovitraps were also set in the selected areas for five days and the larvae were identified to species level. All the collected Ae. albopictus were screened for the presence of Wolbachia using multiplex polymerase chain reaction (PCR) and gene sequencing of Wolbachia surface protein (wsp) gene. Results: A 100 per cent positivity of Wolbachia infection was observed for individual Ae. albopictus screened. For pooled mosquitoes, 73 of the 76 pools (female) and 83 of the 87 pools (male) were positive with Wolbachia infection. The wsp gene sequence of the Wolbachia strain isolated from individual and pooled mosquitoes showed a 100 per cent homology with Wolbachia sp. of Ae. albopictus isolated from various geographical regions. Phylogenetic analysis based on wsp gene fragments showed that the isolates were clustered into groups A and B, respectively. Interpretation & conclusions: The results indicated that Wolbachia infection was widespread in Ae. albopictus population both in female and male Ae. albopictus. All the infected females were superinfected with both A and B strains while the infected males showed a combination of superinfection of A and B strains and single infection of B strain.

Background & objectives: Kala-azar or visceral leishmanisis (VL) is known to be endemic in several States of India including West Bengal (WB). Only meager information is available on the vector dynamics of its vector species, Phlebotomus argentipes particularly in relation to control measure from this State. Hence, a pilot study was undertaken to assess the control strategy and its impact on vector in two endemic districts of WB, India. Methods: Two villages each from the two districts, Maldah and Burdwan, were selected for the study. Seasonal variation of sandflies was observed during pre-monsoon, post-monsoon and winter seasons. Susceptibility test of P. argentipes against DDT and bioassay on DDT sprayed wall and on long lasting insecticide nets (LN) Perma Net ^[®] 2.0 were conducted as per the WHO standard methods. Results: P. argentipes density was high during March to October. Susceptibility status of P. argentipes ranged from 40 to 61.54 per cent. Bioassay test showed 57.89 per cent mortality against LN PermaNet ^[®] -2.0. and 50 per cent against DDT on wall within 30 min of exposure. Interpretation & conclusions: Despite the integrated vector management approach, the sandfly population was high in the study area. The reason could be development of resistance in P. argentipes against DDT and low effectiveness of LN PermaNet ^[®] -2.0. The more pragmatic step will be to conduct large studies to monitor the susceptibility level in P. argentipes against DDT.