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There is increasing interest in the extra-skeletal roles of vitamin D for health and well-being. Poor vitamin D status has been associated with obesity, cardiovascular disease, type 2 diabetes and mental health. Endothelial dysfunction may underscore insulin resistance and hence predispose to both cardiovascular disease (CVD) and type 2 diabetes. The objective of this review was to gain an appreciation of the recent causative evidence linking vitamin D and endothelial function. The PubMed database was searched from 2009 to date. Key words used were vitamin D, supplementation, systemic inflammation, endothelium, endothelial dysfunction and humans. Selected articles were restricted to the English language and to randomized control trials (RCTs) of vitamin D supplementation with direct measures of endothelial function. Final inclusion was based on a quality rating ≥ 3, based on the Jadad score. Ten RCTs met these criteria and were summarized for their outcomes. Only two studies showed an improvement in flow mediated dilatation with vitamin D. Three other studies reported decreases in C-reactive protein, platelet activation inhibitor-1, tissue plasminogen activator or B type natriuretic peptide. Recent evidence from good quality RCTs did not support a beneficial effect of vitamin D on vascular reactivity. Future intervention studies may need to target a higher vitamin D status and longer duration to determine whether the vitamin has a regulatory role in endothelial function.

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Background & objectives: Information on drug resistance tuberculosis is sparse from North-East (N-E) States of India. We undertook this study to detect multi-drug resistant tuberculosis (MDR-TB) among MDR-TB suspects, and common mutations among MDR-TB cases using GenoType MTBDRplus. Methods: All MDR suspect patients deposited sputum samples to peripheral designated microscopy centres (DMC) in North-East States. The district TB officers (DTOs) facilitated the transport of samples collected during January 2012 to August 2012 to our laboratory. The line probe assay to detect common mutations in the rpoB gene for rifampicin (RIF) and katG and inhA genes for isoniazid (INH), respectively was performed on 339 samples or cultures. Results: A total of 553 sputum samples from MDR suspects were received of which, 181 (32.7%) isolates were found to be multi-drug resistant. Missing WT8 along with mutation in codon S531L was commonest pattern for rifampicin resistant isolates (65.1%) and missing WT along with mutations in codon S315T1 of katG gene was commonest pattern for isoniazid resistant isolates (86.2%). Average turn-around time for dispatch of LPA result to these States from cultures and samples was 23.4 and 5.2 days, respectively. Interpretations & conclusions: The MDR-TB among MDR-TB suspects in North-Eastern States of India was found to be 32.7 per cent. The common mutations obtained for RIF and INH in the region were mostly similar to those reported earlier.

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Background & objectives: The presence of CD4+CD8+ (double positive) T cells (DPT) in the target organs of several autoimmune diseases has been reported. The aim of this study was to investigate the pathogenic role of DPT in systemic lupus erythematosus (SLE). Methods: A total of 175 SLE cases and 125 matched healthy controls were investigated for CD3+, CD4+, CD8+ lymphocytes and DPT by flow cytometry. Serum samples from SLE patients and controls were tested for antinuclear antibody (ANA), anti-double strain deoxyribonucleic acid (anti-dsDNA), anti-U1 ribonucleoprotein (anti-U1 RNP), anti-sjogren syndrome A (anti-SSA), anti-ribosomal P protein (anti-rib-P), anti-Smith (anti-Sm), anti-Sjogren syndrome B (anti-SSB), complement 3 (C3) and complement 4 (C4). Results: The DPT median and 5-95 per cent range of SLE cases and healthy controls were 0.50 [0.10-2.60] and 0.80 [0.20-2.74] respectively (P<0.001). SLE patients were divided into a ≥1:1000 subgroup and a <1:1000 subgroup according to the ANA titre. The DPT of the former subgroup was significantly lower than that of the latter (P=0.032). The DPT medians of positive subgroups with anti-dsDNA (P<0.001), anti-U1RNP (P=0.018), anti-SSA (P=0.021) or anti-rib-P (P=0.039) were also significantly lower than the negative subgroups. Likewise, DPT was significantly lower in SLE subgroups with low concentration of C3 or C4 than those with high concentration (P<0.006). Interpretation & conclusions: Our findings show that the DPT cells may play a key suppressive role in the production of autoantibodies in SLE. Direct evidence that DPT regulates the pathogenesis of SLE needs to be investigated in future work.

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Background & objectives: Deficiency of vitamin D, an immunomodulator agent, is associated with increased susceptibility to tuberculosis in adults, but only limited studies are available in the paediatric age group, especially regarding association of vitamin D with type and outcome of tuberculosis. We conducted this study to determine the baseline 25-hydroxy vitamin D levels in children suffering from intrathoracic tuberculosis and its association with type and outcome of tuberculosis. Methods: Children with intrathoracic tuberculosis, diagnosed on the basis of clinico-radiological criteria, were enrolled as part of a randomized controlled trial on micronutrient supplementation in paediatric tuberculosis patients. Levels of 25-hydroxy vitamin D were measured in serum samples collected prior to starting antitubercular therapy by chemiluminescent immunoassay technology. Results: Two hundred sixty six children (mean age of 106.9 ± 43.7 months; 57.1% girls) were enrolled. Chest X-ray was suggestive of primary pulmonary complex, progressive disease and pleural effusion in 81 (30.5%), 149 (56%) and 36 (13.5%) subjects, respectively. Median serum 25-hydroxy vitamin D level was 8 ng/ml (IQR 5, 12). One hundred and eighty six (69.9%) children were vitamin D deficient (serum 25-hydroxy vitamin D <12 ng/ml), 55 (20.7%) were insufficient (12 to <20 ng/ml) and 25 (9.4%) were vitamin D sufficient (≥ 20 ng/ml). Levels of 25-hydroxy vitamin D were similar in all three types of intrathoracic tuberculosis, and in microbiologically confirmed and probable cases. Levels of 25-hydroxy vitamin D did not significantly affect outcome of the disease. Children who were deficient or insufficient were less likely to convert (become smear/culture negative) at two months as compared to those who were 25-hydroxy vitamin D sufficient ( p <0.05). Interpretation & conclusions: Majority of Indian children with newly diagnosed intrathoracic tuberculosis were deficient in vitamin D. Type of disease or outcome was not affected by 25-hydroxy vitamin D levels in these children. However, children who did not demonstrate sputum conversion after intensive phase of antitubercular therapy had lower baseline 25-hydroxy vitamin D levels as compared to those who did.

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Background & objectives: The National AIDS Control Organization (NACO) of India has been providing free ARV (antiretroviral) drugs since 2004. b0 y 2012, 486,173 patients had received treatment through the antiretroviral therapy (ART) centres. The objective of this observational study was to assess the factors determining survival of patients on ART under routine programme conditions in an ART centre in north India five years after its inception. Methods: Treatment naive HIV positive patients who were enrolled in the ART centre between May 2009 and May 2010 and started on ART as per the Revised NACO guidelines 2009, were included in the study and outcome was assessed after two years of follow up. Results: A total of 1689 patients were included in the analysis, of whom 272 (16.10%) expired, 205 (12.13%) were lost to follow up (LFU), 526 (31.14%) were transferred out to other facilities and 686 (40.63%) were alive at the end of two years. Majority (92%) of the deaths occurred in the first six months of therapy. Age >30 yr, male gender, poor functional status, haemoglobin level <11 g/dl, body weight <45 kg and CD4 count <100/μl at baseline had significantly higher relative hazard of death. Most LFU also occurred in the first six months and these patients had significantly low CD4 count, weight, haemoglobin level and higher number of patients in Stages III and IV as compared to those who survived. Interpretation & conclusions: The study findings revealed poor survival in the first six months of therapy especially in those with severe immunosuppression. This emphasizes the need for early enrolment into the programme. The high LFU occurring early after initiation of therapy suggests the urgent need to build an efficient patient retrieval system in the programme.

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Background & objectives: New Delhi metallo β-lactamase-1 (NDM-1) producing Pseudomonas aeruginosa isolates are potential threat to human health. This study was conducted to detect the presence of bla_NDM-1 in carbapenem resistant P. aeruginosa in a tertiary care center in southern India. Methods: Sixty one carbapenem resistant clinical isolates of a total of 212 P. aeruginosa isolates cultured during the study period were screened for the presence of NDM-1by PCR. Clinical characteristics of the NDM-1 positive isolates were studied and outcome of the patients was followed up. Results: Of the 61 isolates, NDM-1 was detected in four isolates only. These were isolated from patients in the intensive care units and chest medicine ward. The source specimens were pus, sputum, bronchoalveolar lavage and endotracheal aspirate. The NDM-1 producers were susceptible only to polymyxin B. Only one patient responded to polymyxin B therapy, while the others succumbed to the infection. Conclusion: These findings reveal that NDM-1 is not a major mechanism mediating carbapenem resistance in P. aeruginosa in this centre. However, continuous surveillance and screening are necessary to prevent their dissemination.

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Background & objectives: Leptin resistance oriented hyperleptinaemia is a common problem in obese subjects in association with hypercholesterolaemia. The most common target for hypercholesterolaemia is impaired low density lipoprotein receptor (LDLR). This study was carried out to investigate whether any alteration in LDLR expression could explain the occurrence of hypercholesterolaemia in the event of hyperleptinaemia. Methods: Expression of LDLR and SREBP2 (sterol regulatory element binding protein 2) were examined in HepG2 cells by RT-PCR and Western blotting. JAK2 inhibitor II was used to verify the effect of JAK-STAT (Janus Kinase-Signal Transducer and Activator of Transcription) pathway (common mediator for cytokine signaling). Co-localization of LDLR and insulin receptor (IR) was examined by confocal microscopy. Results: Leptin was found to reduce the expression of LDLR and its transcription factor SREBP2. On the other hand, a weak signal for stimulation of LDLR by leptin was noted to be mediated by JAK2 pathway. But the joint effect of the two signaling pathways kept LDLR only in depressed mode in presence of leptin. Confocal microscopy showed that LDLR made an intensively co-localized complex with insulin receptor in presence of leptin. Interpretation & conclusions: Our results show that though leptin stimulates LDLR expression very weakly through JAK-STAT signaling pathway, it mainly imposes inhibition on LDLR expression by inhibiting transcription factor SREBP2. The inter-association between LDLR and IR may be a reason to render LDLR functionally inactive in presence of leptin.

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Background & objectives: Serum prostate specific antigen (PSA) levels are known to vary with race and ethnicity, environmental factors, lifestyle, metabolic and physiologic changes and advancing age. This study was designed to determine age specific serum PSA level in healthy Indian men and its comparison with that reported in different populations of the world. Methods: A total of 1300 adult men who attended Executive Health Check-up programme in a tertiary care hospital in Haryana, India, were included in the study. Forty seven men were excluded from the analysis because of urological conditions affecting PSA values. Overall, 1253 men were analyzed for age specific PSA values. Results: The age specific reference range of serum PSA values was 0.71 ng/ml in those younger than 40 yr; 0.85 ng/ml in 40-49 yr; 1.13ng/ml in 50-59 yr group; 1.45 ng/ml in 60-69 yr group; 1.84 ng/ml in 70-79 yr group and 2.35 ng/ml in men older than 80 yr. Interpretation & conclusions: Our study provided the age-specific reference range of serum PSA in healthy men in India. The data suggested that the PSA levels were associated with increasing age.

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Background & objectives: Candida albicans is the most common aetiological agent in funguria cases commonly observed in hospitalized patients. But a few reports are available from India where non-albicans Candida species have accounted for >50 per cent of urinary Candida isolates. We undertook this study to know the fungal profile amongst funguria cases. Methods: A total of 123 consecutive fungal isolates obtained from clinically suspected cases of urinary tract infection from April to September, 2013, were included. Yeast species was identified by standard phenotypic methods. Antifungal susceptibility testing of yeast was performed for fluconazole (25 μg) by disc diffusion method as per Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: The male to female ratio was 0.92. The mean age of patients was 42.7 ± 18.9 yr. C. tropicalis (58.5%) was the most common fungal agent followed by C. albicans (30.1%). Only one isolate of C. tropicalis was resistant to fluconazole. Interpretation & conclusions: C. tropicalis and C. albicans were the predominant fungal pathogens responsible for urinary tract infection. Less resistance to fluconazole observed in the study may be due to restricted use of fluconazole in this area.

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Background & objectives: Immune activation and inflammation play critical roles in the stressful environmental conditions like high altitude, extreme cold, etc. Human leukocyte antigen-G (HLA-G) is a non classical major histocompatiblity complex class I (MHC class- I) protein, upregulated in the context of transplantation, malignancy and inflammation. We hypothesized serum HLA-G as a possible stress biomarker and studied levels of soluble form of HLA-G (sHLA-G) in Indian Antarctic expeditioners. Methods: sHLA-G ELISA was performed in the serum of summer (n=27) and winter (n=22) Indian Antarctic expeditioners. The summer expeditioners were evaluated at three different time points, i.e. before leaving India, after one month ship borne journey, and after staying one month at Indian research base, Maitri in Antarctica, while winter expeditioners were evaluated at five different time points, i.e. before leaving India, and in the month of March, May, August and November at Antarctica. Results: o0 ne month ship borne journey did not cause any significant change in the sHLA-G level as compared to the baseline level of the summer expeditioners. sHLA-G levels were not changed significantly in the months of March, May, August and November as compared to the baseline level of the winter expeditioners. Interpretation & conclusions: Our results indicated that the extreme conditions of Antarctica did not cause any significant change in the sHLA-G level in both summer and winter expeditioners.

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Background & objectives: Culex quinquefasciatus is the principal vector of lymphatic filariasis (LF). Application of alternative vector control methodologies are aimed at reduction of mosquito breeding sites and biting activity through the use of biological control methods. In the present study, functional response of aquatic Hemipteran backswimmer, Anisops sardea was assessed against Cx. quinquefasciatus larvae in laboratory bioassay. Methods: The functional respons of A. sardea was assessed against III ^rd instar larvae of Cx. quinquefasciatus. Respective handling times and coefficient of attack rates were determined by a non linear polynomeal regression equation. Results: The results of rates of predation in variable prey densities exhibited a 'linear rise to plateau curve', associated with 'Type -II' functional response. The logistic regression estimated a significant negative linear parameter (P ₁ <0) which also supported the same observation. Associated 'attack rates' and 'handling times' were also calculated using the Holling Disc Equation. Interpretation & conclusions: The results of present experiments indicate that A. sardea can be used as a biocontrol agent against the larval forms of Cx. quinquefasciatus in temporarily available breeding places of mosquito with relatively clear water. However, a detailed field study has to be done to confirm these findings.

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Background & objectives: Selection of an insecticide and its appropriate formulation is a prerequisite of formulating any chemical control strategy against vectors. A hut scale field trial was carried out to study the effectiveness of house spraying with capsule suspension (CS) formulation of lambdacyhalothrin in comparison with its wettable powder (WP) formulation on mortality, density and behaviour of malaria vector in Malkangiri district, Odisha, India. Methods: The two formulations were tested at 20 and 30 mg (a.i.)/m ² for their effectiveness in terms of deterrence, excito-repellency, blood-feeding success, mortality and residual activity against Anopheles fluviatilis, the major malaria vector, in experimental huts in Malkangiri district, Odisha State, India. Results: Both CS and WP formulations prevented the entry of An. fluviatilis in to the sprayed huts by >90 per cent for >6 months, the entire peak malaria transmission season in the area. The exit rate increased (90-99%) with different treatments and the feeding rate was reduced (91-97%). There was no significant difference between WP 30, CS 20 and CS 30 mg/m ² in these respects. However, WP 20 mg/m ² caused a lesser effect than the other three groups. The formulations or the dosages differed only in causing vector mortalities. Overall, the total mortality rate of An. fluviatilis was higher in the huts sprayed with CS 30 (58%) than the huts sprayed with CS 20 (48%), WP 20 (37%) and WP 30 mg/m ² (47%). Interpretation & conclusions: Considering the duration of residual action and the effect on entry, exit, feeding and mortality of An. fluviatilis, the dosage 20 mg/m ² of CS formulation of lambdacyhalothrin could be considered for further use.

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