Background & objectives: The risk estimation for foetal aneuploidies in the first trimester of pregnancy uses reference curves based on western data. The objective of this study was to construct the reference curves of first-trimester foetal aneuploidy screening parameters for the Indian women. Methods: Cross-sectional data were obtained from 1204 singleton pregnancies between the crown-rump length (CRL) of 40-84 mm. Linear regression models were constructed; the mean, median and standard deviation were derived as a function of CRL. Results: The mean value of CRL was 61.3 mm. The regression analysis showed a significant correlation between all variables and CRL (P< 0.001). There was a positive correlation of CRL with nuchal translucency (NT) (y=0.010x+0.629, R²=0.116) and pregnancy-associated plasma protein-A (PAPP-A) (y=0.107x−1.079, R²=0.173), whereas inverse correlation was seen with free β-human chorionic gonadotropin (β-hCG) (y=−0.409x+75.025, R²=0.018) and Doppler parameters pulsatility index (PI) (y=−0.008x+1.924 R²=0.053). The centile charts of NT, PAPP-A, free β-hCG and uterine artery (Ut A) Doppler PI were constructed. Interpretation & conclusions: The reference centile charts of first trimester aneuploidy screening along with Doppler parameters were derived in Indian pregnant women. These centile charts may be used as a reference for clinical use in Indian population.

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Background & objectives: Smokeless tobacco (SLT) consumption is a global health issue with about 350 million users and numerous adverse health consequences like oral cancer and myocardial disorders. Hence, cessation of SLT use is as essential as smoking cessation. An update on the available literature on SLT cessation intervention studies is provided here. Methods: Through an extensive literature search on SLT cessation intervention studies, using keywords such as smokeless tobacco, cessation, interventions, quitlines, brief advice, nicotine replacement therapy, nicotine gum, nicotine lozenge, nicotine patch, bupropion, varenicline, mHealth, etc., 59 eligible studies were selected. Furthermore, efficacy of the interventions was assessed from the reported risk ratios (RRs) [confidence intervals (CIs)] and quit rates. Results: Studies were conducted in Scandinavia, India, United Kingdom, Pakistan and the United States of America, with variable follow up periods of one month to 10 years. Behavioural interventions alone showed high efficacy in SLT cessation; most studies were conducted among adults and showed positive effects, i.e. RR [CI] 0.87 [0.7, 1.09] to 3.84 [2.33, 6.33], quit rate between 9-51.5 per cent, at six months. Regular telephone support/quitlines also proved beneficial. Among pharmacological modalities, nicotine lozenges and varenicline proved efficacious in SLT cessation. Interpretation & conclusions: Globally, there is limited information available on SLT cessation intervention trials, research on which must be encouraged, especially in the low-resource, high SLT burden countries; behavioural interventions are most suitable for such settings. Appropriate training/sensitization of healthcare professionals, and school-based SLT use prevention and cessation programmes need to be encouraged.

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Human parvovirus B19 (B19V) causes myriads of clinical diseases; however, owing to lack of awareness and undetermined clinical impact, it has failed to become a virus pathogen of global concern. Cryptically, B19V causes significant morbidity and mortality. Half of the world population and 60 per cent of Indians are known to be serologically naive and are at risk of acquiring B19V infections. Cumulatively, our data showed 21.3 per cent B19V-infected patients with juvenile chronic arthropathy, recurrent abortions, multi-transfused thalassaemia and leukaemia. In addition, B19V-infected cases that ended fatally included patients with pure red cell aplasia, fulminant hepatitis and haemophagocytic syndrome. Novel clinical associations of B19V observed were amegakaryocytic thrombocytopaenia, myositis and non-occlusive ischaemic gangrene of bowel. B19V possesses multiple receptors which are distributed widely in human tissues. Vascular endothelial cell infection by B19V causes endothelialitis and vasculitic injuries besides antibody-dependent enhancement which empowered B19V to cause multiorgan diseases. Owing to lack of suitable animal model for B19V, true causal role remains to be determined, but numerous reports on B19V infections substantiate a causal role in multiorgan diseases. Hence, B19V infections need to be recognized, investigated and treated besides making efforts on vaccine developments.

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Background & objectives: Psoriasis is a chronic inflammatory skin disease with unknown aetiology. So far studies have confirmed that interleukins, pro-inflammatory factors and T-cell activation play major role in the development of disease. Interleukin-17 (IL-17) a T helper inflammatory cytokine, was found to be positively correlated with severity of psoriasis. However, the specific mechanism has not been clarified. IL-17A and IL-17F are group members of IL17 family cytokines and found to be located adjacent to one another on the same human chromosome, 6p12. The present study was designed to identify the association between IL-17A and IL-17F gene polymorphism with susceptibility of psoriasis in north Indian population. Methods: A total of 166 psoriasis patients and 150 healthy controls were genotyped for IL-17A and IL-17F gene polymorphism by amplification refractory mutation system-polymerase chain reaction method. One single nucleotide polymorphism (SNP) was analysed in IL-17A (rs10484879) and one SNP in IL-17F (rs763780) to look for an association with psoriasis. Results: Our study indicated decreased frequency of IL-17A (rs10484879) G allele (51.8 vs. 65.0%), and IL-17F (rs763780) C allele (36.5 vs. 45.7%) in psoriatic patients as compared to healthy controls. Interpretation & conclusions: The present findings suggest that IL-17A (rs10484879) G/T and IL-17F (rs763780) C/T gene polymorphisms may contribute in pathogenesis of psoriasis. Further studies need to be done to confirm these findings.

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Background & objectives: Although febrile illnesses are a frequent cause of consultation and hospitalization in low- and middle-income countries (LMICs), research has mainly focused on acute febrile illnesses (AFIs). In contrast, there are limited data on the causes of persistent febrile illnesses (PFIs) in LMIC. Lack of clarity on the differential diagnosis of PFIs in the rural tropics leads to the absence of diagnostic guidance tools. Methods: In this study, a review of the potential causes of persistent fever defined as fever of more than seven days was done in Nepal, with a focus on nine pathogen-specific conditions. The current knowledge on their burden, distribution and diagnosis was summarized. Results: Limited data were found on the incidence and public health burden of leptospirosis, murine typhus and brucellosis due to the absence of diagnostic tools outside reference laboratories and the overlap of signs and symptoms with other febrile conditions. The incidence of malaria and visceral leishmaniasis (VL) was found to be decreasing in Nepal, with some changes of the geographical areas at risk. Interpretation & conclusions: This review indicates a need for more research on the causes of PFIs in Nepal and in the region and for the development of clinical guidance tailored to current local epidemiology. Guidance tools should include specific clinical features (e.g. eschar), results of rapid diagnostic tests (e.g. malaria, VL), appropriate indications for more sophisticated tests (e.g. abdominal ultrasound, polymerase chain reaction) and recommendations for adequate use of empirical treatment.

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Background & objectives: The diagnostic value of fractional exhaled nitric oxide (FeNO) in patients with asthma remains controversial. This study was aimed to re-evaluate the diagnostic value of FeNO in specific groups with asthma and identify potential factors associated with FeNO. Methods: FeNO measurement and bronchial provocation test (BPT) or bronchodilator test (BDT) were performed in patients with suggestive symptoms for asthma. Correlation analysis was performed, and receiver-operating characteristic (ROC) curves and area under the curve (AUC) were calculated to evaluate the accuracy of FeNO in diagnosis. Results: A total of 265 (66.3%) patients with asthma were identified in 400 individuals suspected to have asthma from October 2014 to June 2015. Positive correlations of gender (r=0.138, P=0.005), atopy (r=0.598, P <0.001) and rhinitis (r=0.485, P <0.001) but negative correlations of age (r=−0.220, P <0.001) and the cumulative methacholine dosage with a 20 per cent decrease in forced expiratory volume in one second (r=−0.197, P <0.001) with FeNO were found. AUC of FeNO in whole population and patients with atopy and rhinitis was 0.728 [95% confidence interval (CI) 0.675-0.781, P <0.001] and 0.752 (95% CI 0.640-0.865, P <0.001), while the cut-offs were 23.5 and 44.5 parts per billion (ppb), respectively, rendering sensitivities, specificities, positive predictive value and negative predictive value of 79.9, 54.7, 77.9, 58.1 and 78.7, 67.9, 89.2 and 48.7 per cent, respectively. The cut-off of FeNO with specificity of 90 per cent (FeNO₉₀) for all patients and a sub-group of patients with atopy and rhinitis was 59.5 and 90.5 ppb, respectively, while FeNO₉₀decreased by 12 ppb with every 10 years. Interpretation & conclusions: Our findings show that the diagnostic value of FeNO varies in different groups of patients with asthma, thus, the cut-off point should be adjusted in different asthmatic sub-populations. A cut-off point of FeNO with a specificity >90 per cent could decrease the false-positive rate.

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Background & objectives: Dyslipidaemia is a major contributor to cardiovascular morbidity, which is increased in HIV. Data on dyslipidaemia in Indians with HIV are scant. This study was undertaken to determine the predictors of dyslipidaemia and lipoatrophy in Indians with HIV infection and their relation with body composition parameters. Methods: A total of 382 consecutive patients with HIV infection were screened, of whom 257 clinically stable patients, without any acute comorbidity, having at least one year follow up underwent biochemical and DEXA analysis. Results: The most common dyslipidaemia was hypertriglyceridaemia (47.08%), followed by hypercholesterolaemia [total cholesterol (TC)] (38.91%) and low high-density lipoprotein (HDL) cholesterol (38.52%), in patients having median age 37 (32-42) yr and HIV duration 57 (33-101) months. Patients with at least one dyslipidaemia (78.99%) had significantly higher insulin resistance (IR), per cent body fat, per cent trunk fat (PTF) and trunk limb fat ratio (TLFR). Baseline CD4 count and delta CD4 count (change in CD4 count 6-12 months following ART) had significant inverse correlation with triglycerides and TC. Patients with highest triglycerides and cholesterol quartiles had significantly higher immune reconstitution, metabolic syndrome, IR, trunk fat mass (FM), PTF and TLFR, with comparable total FM. Logistic regression revealed that body mass index, HIV duration and PTF were independent predictors of hypertriglyceridaemia, with only PTF being significant predictor of hypercholesterolaemia. Every unit increase in PTF was associated with 13 and 4.1 per cent increased hypertriglyceridaemia and hypercholesterolaemia. Lipoatrophy was present in 8.57 per cent patients and was a poor predictor of dyslipidaemia. Interpretation & conclusions: High occurrence of dyslipidaemia was observed in patients with HIV on anti retroviral therapy. Central adiposity (TFM) was the most important predictor of dyslipidaemia in these patients.

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Background & objectives: Oxidative stress (OS) is associated with numerous components of metabolic syndrome (MetS). This study was aimed to investigate if hydrogen peroxide (H₂O₂) as the reactive oxygen species was capable of depicting OS in MetS, and If MetS patients showed DNA damage in the form of DNA strand breaks (DSB). Methods: A total of 160 participants (90 males, 70 females) ≥20 yr of age were categorized into four groups based on the number of MetS risk parameters (n=40 in each group). Sugar and lipid profile, H₂O₂concentration in blood and DNA-strand breaks were measured. Results: DSB was significantly more in those with MetS (n=40) than those without (n=120) whereas H₂O₂levels were the same in both the study groups. The number of DSB differed significantly between the control and 3 risk factor groups. DSB was also higher in groups with 2 and 1 risk factors compared to 0 risk but the difference was not significant. H₂O₂ level was higher in groups with 3, 2 and 1 risk factors compared to 0 risk group but the difference was not significant. The H₂O₂level correlated positively with triglyceride values but not with other MetS risk parameters. There was no significant correlation between DSB and MetS risk parameters. Interpretation & conclusions: Our findings showed a cumulative and synergistic effect of the risk factors of MetS on DSB. Individuals with three risk parameters had a greater effect on DNA damage than in those with two or one risk parameter. Although plasma H₂O₂level increased with an increase in the fat depots, use of H₂O₂to depict OS in MetS should be coupled with an adjunct and estimation of DSB in peripheral blood lymphocytes may be used as indicator of OS in MetS patients.

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