Globally, tuberculosis (TB) still remains a major public health problem. India is a high TB burden country contributing to 26 per cent of global TB burden. During 1944-1980, TB became treatable and short-course chemotherapy emerged as the standard of care. When TB elimination seemed possible in the early 1980s, global human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) pandemic resulted in a resurgence of TB. Widespread occurrence of multidrug-resistant and extensively drug-resistant TB (M/XDR-TB) is threatening to destabilize TB control globally. Atypical clinical presentation still poses a challenge. Disseminated, miliary and cryptic TB are being increasingly recognized. Availability of newer imaging modalities has allowed more efficient localization of lesions and use of image guided procedures has facilitated definitive diagnosis of extrapulmonary TB. Introduction of liquid culture, rapid drug-susceptibility testing (DST), molecular diagnostic methods has helped in rapid detection, speciation and DST profiling of Mycobacterium tuberculosis isolates. While treatment of TB and HIV-TB co-infection has become simpler, efforts are on to shorten the treatment duration. However, drug toxicities and drug-drug interactions still constitute a significant challenge. Recently, there has been better understanding of anti-TB drug-induced hepatotoxicity and its frequent confounding by viral hepatitis, especially, in resource-constrained settings; and immune reconstitution inflammatory syndrome (IRIS) in HIV-TB. Quest for newer biomarkers for predicting a durable cure, relapse, discovery/repurposing of newer anti-TB drugs, development of newer vaccines continues to achieve the goal of eliminating TB altogether by 2050.

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Background & objectives: Little data are available regarding the frequencies of the blood group antigens other than ABO and RhD in the Indian population. Knowledge of the antigen frequencies is important to assess risk of antibody formation and to guide the probability of finding antigen-negative donor blood, which is especially useful when blood is required for a patient who has multiple red cell alloantibodies. This study was carried out to determine the frequencies of the D, C, c, E, e, K, k, Fy ^a , Fy ^b , Jk ^a , Jk ^b , M, N, S and s antigens in over 3,000 blood donors. Methods: Samples from randomly selected blood donors from Delhi and nearby areas (both voluntary and replacement) were collected for extended antigen typing during the period January 2009 to January 2010. Antigens were typed via automated testing on the Galileo instrument using commercial antisera. Results: A total of 3073 blood samples from donors were phenotyped. The prevalence of these antigens was found to be as follows in %: D: 93.6, C: 87, c: 58, E: 20, e: 98, K: 3.5, k: 99.97, Fy ^a : 87.4, Fy ^b : 57.6, Jk ^a : 81.5, Jk ^b : 67.4, M: 88.7, N: 65.4, S: 54.8 and s: 88.7. Interpretation & conclusions: This study found the prevalence of the typed antigens among Indian blood donors to be statistically different to those in the Caucasian, Black and Chinese populations, but more similar to Caucasians than to the other racial groups.

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Background & objectives: Patients with head and neck cancer (HNC) undergoing chemoradiotherapy (CRT) suffer from fatigue causing a decrease in functional capacity and quality of life (QoL). Limited research in the field of exercise training among these patients demanded the need for this study to assess the effects of exercise training on functional capacity and quality of life. Methods: A randomized controlled trial was conducted on 48 patients with HNC undergoing CRT. The exercise group received an individually tailored, supervised, exercise programme for six weeks, while the control group did not receive any form of exercise. Functional capacity and QoL were assessed at baseline and at the end of the intervention using the six minute walk distance (6MWD) and medical outcomes survey short form 36 (SF 36). Results: The mean age of patients was 52 yr with 42 males. After six weeks, the 6MWD improved by 42 metres (P<0.05) in the exercise group while the control group showed a decrease by 96 metres (P<0.001). There was an improvement on the mental component score (MCS) of SF36 for the exercise group (4.8; P<0.05) and the physical component score (PCS) remained almost the same, while a decrease in PCS and MCS was seen in the control group (-5.9; P=0.064 and -17.3; P<0.05). When 6MWD and SF36 were compared between the groups, there was a statistically significant difference (P<0.001) seen after six weeks. Interpretation & conclusions: Our results showed that the functional capacity and QoL decreased among those not receiving a supervised exercise program, while exercise training improved functional capacity and QoL in HNC patients undergoing CRT.

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Background & objectives: Banaba (Lagerstroemia speciosa L.) extracts have been used as traditional medicines and are effective in controlling diabetes and obesity. The aim of this study was to evaluate the anti-HIV property of the extracts prepared from the leaves and stems of banaba, and further purification and characterization of the active components. Methods: Aqueous and 50 per cent ethanolic extracts were prepared from leaves and stems of banaba and were evaluated for cytotoxicity and anti-HIV activity using in vitro reporter gene based assays. Further, three compounds were isolated from the 50 per cent ethanolic extract of banaba leaves using silica gel column chromatography and characterization done by HPLC, NMR and MS analysis. To delineate the mode of action of the active compounds, reverse transcriptase assay and protease assay were performed using commercially available kits. Results: All the extracts showed a dose dependent inhibition of HIV-1-infection in TZM-bl and CEM-GFP cell lines with a maximum from the 50 per cent ethanolic extract from leaves (IC ₅₀ = 1 to 25 μg/ml). This observation was confirmed by the virus load (p24) estimation in infected CEM-GFP cells when treated with the extracts. Gallic acid showed an inhibition in reverse transcriptase whereas ellagic acid inhibited the HIV-1 protease activity. Interpretation & conclusions: The present study shows a novel anti-HIV activity of banaba. The active components responsible for anti-HIV activity were gallic acid and ellagic acid, through inhibition of reverse transcriptase and HIV protease, respectively and hence could be regarded as promising candidates for the development of topical anti-HIV-1 agents.

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Background & objectives: Aplastic anaemia is a rare haematological disorder characterized by pancytopenia with a hypocellular bone marrow. It may be inherited/genetic or acquired. Acquired aplastic anaemia has been linked to many drugs, chemicals and viruses. Cytogenetic abnormalities have been reported infrequently with acquired aplastic anaemia. Majority of the studies are in adult patients from the West. We report here cytogenetic studies on paediatric patients with acquired aplastic anaemia seen in a tertiary care hospital in north India. Methods: Patients (n=71, age 4-14 yr) were diagnosed according to the guidelines of International Agranulocytosis and Aplastic Anaemia Study. Conventional cytogenetics with Giemsa Trypsin Giemsa (GTG) banding was performed. Karyotyping was done according to the International System for Human Cytogenetics Nomenclature (ISCN). Results: Of the 71 patients, 42 had successful karyotyping where median age was 9 yr; of these 42, 27 (64.3%) patients had severe, nine (21.4%) had very severe and six (14.3%) had non severe aplastic anaemia. Five patients had karyotypic abnormalities with trisomy 12 (1), trisomy 8 (1) and monosomy 7 (1). Two patients had non numerical abnormalities with del 7 q - and t (5:12) in one each. Twenty nine patients had uninformative results. There was no difference in the clinical and haematological profile of patients with normal versus abnormal cytogenetics although the number of patients was small in the two groups. Interpretation & conclusions: Five (11.9%) patients with acquired aplastic anaemia had chromosomal abnormalities. Trisomy was found to be the commonest abnormality. Cytogenetic abnormalities may be significant in acquired aplastic anaemia although further studies on a large sample are required to confirm the findings.

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Background & objectives: Human papillomavirus (HPV) is the necessary cause of cervical cancer and Chlamydia trachomatis (CT) is considered a potential cofactor in the development of cervical intraepithelial neoplasia (CIN). The objective of this pilot study was to determine the association of CT infection with HPV, other risk factors for cervical cancer, and CIN in symptomatic women. Methods: A total of 600 consecutively selected women aged 30-74 yr with persistent vaginal discharge, intermenstrual/postcoital bleeding or unhealthy cervix underwent conventional Pap smear, Hybrid Capture 2^® (HC2) testing for HPV and CT DNA and colposcopy, with directed biopsy of all lesions. Results: HPV DNA was positive in 108 (18.0%) women, CT DNA in 29 (4.8%) women. HPV/CT co-infection was observed in only four (0.7%) women. Of the 127 (21.2%) women with Pap >ASCUS, 60 (47.2%) were HPV positive and four (3.1%) were CT positive. Of the 41 women with CIN1 lesions, 11 (26.8%) were HPV positive, while two were CT positive. Of the 46 women with CIN2+ on histopathology, 41 (89.1%) were HPV positive, two (4.3%) were CT positive and one was positive for both. The risk of CIN2+ disease was significantly increased (P<0.05) by the following factors: age <18 yr at first coitus, HPV infection and a positive Pap smear. Older age (>35 yr), higher parity, use of oral contraceptives or smoking did not show any significant association with HPV or abnormal histopathology. Parity >5 was the only risk factor positivity associated with CT infection (P<0.05). Interpretation & conclusions: Our findings showed that CT infection was not significantly associated with CIN, and most of its risk factors, including HPV infection, in symptomatic women. Longitudinal studies with carefully selected study sample would be able to answer these questions.

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The need to focus healthcare expenditures on innovative and sustainable health systems that efficiently use existing effective therapies are the major drivers stimulating Comparative Effectiveness Research (CER) across the globe. Lack of adequate access and high cost of essential medicines and technologies in many countries increases morbidity and mortality and cost of care that forces people and families into poverty due to disability and out-of-pocket expenses. This review illustrates the potential of value-added global health care comparative effectiveness research in shaping health systems and health care delivery paradigms in the "global south". Enabling the development of effective CER systems globally paves the way for tangible local and regional definitions of equity in health care because CER fosters the sharing of critical assets, resources, skills, and capabilities and the development of collaborative of multi-sectorial frameworks to improve health outcomes and metrics globally.

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Background & objectives: ADAM33 is a member of a family of genes that encode membrane-anchored proteins with a disintegrin and a metalloprotease domain, primarily expressed in lung fibroblasts and bronchial smooth muscle cells. ADAM33 has been identified as a risk factor for asthma and is known as a gene associated with airway remodelling. The present study was conducted with the aims to investigate the expression of ADAM33 protein in patients of asthma and non-asthmatic controls, and to assess if the expression of ADAM33 protein relates with severity of asthma. Methods: A total of 35 subjects, including 27 patients with asthma and eight non-asthmatic controls were included using Global Initiative for Asthma guidelines 2005. Bronchial biopsy tissues were collected and paraffin sections were made to store all study samples. Immunohistochemistry was performed using standardized protocol. Results: An increase in expression of ADAM33 protein was observed in the epithelium, smooth muscle and mesenchymal cells of asthma cases when compared to controls but there was no relationship with severity of asthma. Interpretation & conclusions: A higher expression of ADAM33 protein was seen in asthma patients compared to controls. Large prospective studies need to be done with adequate study design to confirm these preliminary finding.

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Background & objectives: Drug resistance is the primary cause of failure in the treatment of cancers. It has been suggested that the enhancement of DNA repair capability may be responsible for the drug resistance of the tumour cells, and poly(ADP-ribosyl)ation plays an important role in DNA repair. This study investigated the effect of PARP inhibitor 3-aminobenzamide (3-AB) on the cisplatin resistance and proliferation of the cisplatin-resistant ovarian cancer C13 ^* cells in vitro. Methods: C13 ^* cells were treated with various concentrations of 3-AB in vitro. MTT assay was used to determine the effect of 3-AB on the cisplatin sensitivity and proliferation of cells. The expression levels of PARP-1 mRNA and protein in the C13 ^* cells were examined using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, and changes caused by 3-AB treatment were investigated. Immunofluorescence microscopy was used to detect the localization and expression of the PARP-1 proteins before and after treatment with 5 mmol/l 3-AB. Results: The inhibitory ratio and the cisplatin sensitivity of C13 ^* cells significantly increased with the increase of the concentration of 3-AB (P<0.05). The RT-PCR analysis revealed that the expression of PARP-1 mRNA was decreased when platinum (Pt) and 3-AB were combined. The expression levels of PARP-1 protein were decreased by 23.15 ± 2.53, 59.11 ± 2.23 and 73.24 ± 3.88 per cent, respectively, in C13 ^* cells with the increase of the concentration of 3-AB (P<0.05). The immunofluorescence microscopy results indicated that the expression level of PARP-1 protein was significantly decreased after treatment with 3-AB (P,<0.05). Interpretation & conclusions: 3-AB inhibited the proliferation activity of C13 ^* cells, and increased the cellular sensitivity to cisplatin. Our findings show that the PARP inhibitor 3-AB can downregulate the expression of PARP-1 at transcriptional and translational levels in C13 ^* cells.

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Background & objectives: Entomological surveillance of the dengue vectors using pupal productivity as indicators can be helpful in effective management. On this basis, an assessment was made on the relative importance of the larval habitats of Aedes mosquitoes in Kolkata, an endemic zone for dengue in West Bengal, India. Methods: Monthly collection of larvae and pupae of Aedes from larval habitats categorized as earthen, plastic and porcelain containers and tyres, was carried out from selected sites. Pupal weight was recorded and degree of sexual dimorphism was calculated. The data on pupal weight, sexual dimorphism and immature density were used for regression analysis. Results: The number of positive sites for each type of larval habitats varied with months and mosquito species. Based on mean density per month, the plastic containers were the most productive habitats and the tyres were least productive for both Aedes species. The pupal weight of both Ae. aegypti and Ae. albopictus varied with the relative density and type of larval habitats. Significant differences in pupal productivity, positive sites and the proportion of pupae were observed in the habitats. Species-specific differences in the degree of dimorphism were noted with the females being larger in size than males, irrespective of the habitats. Interpretation & conclusions: Pupal productivity of Aedes mosquitoes in Kolkata differed in terms of the type of the larval habitats with the immature density affecting the body size of the adults. This habitat-based study is a pioneer effort considering Kolkata and calls for a management plan for source reduction of these habitats to minimize Aedes mosquitoes and thus potential risk of dengue.

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