BackgroundIncreased awareness amongst large population groups is a major determinant for the prevention of diabetes and its complications as well as related metabolic disorders. Knowledge and attitude are the principal markers of awareness that need to be studied in various population groups in specific racial and cultural contexts. The present study was undertaken to explore knowledge, attitude and practice (KAP) regarding -diabetes mellitus (DM) among nondiabetic (nonDM) and type 2 diabetes mellitus (T2DM) patients in Bangladesh.MethodsA cross-sectional study was conducted among 18,697 adults (aged 18 years and above; 7796 male and 10,901 female; 6780 nonDM and 11,917 T2DM) selected purposively from the OPD of 19 healthcare centres in and around Dhaka and in northern parts of Bangladesh. KAP were assessed by a pre-structured, interviewer-administered questionnaire and categorised using predefined scores of poor (mean + 1 SD). Univariate and bivariate statistical analysis were done as appropriate. Multivariate linear regression was done to examine the association between diabetes related KAP and other covariates.ResultsThe mean (±SD) age (years) of all the study participants was 46 ± 14, mean BMI 24.4 ± 4.1 and mean waist-hip ratio (WHR) was 0.93 ± 0.07. The proportion of poor, average and good knowledge scores among T2DM subjects were 17%, 68% and 15% respectively. The corresponding values for attitude score were 23%, 67% and 10% respectively. The KAP regarding diabetes was found to be better among people who were living with diabetes compared to their counterparts. DM males showed better knowledge and practice regarding diabetes, compared to nonDM counterparts (M ± SD; 44.18 ± 16.13 vs 40.88 ± 15.62, p = <0.001; 66.00 ± 29.68 vs 64.21 ± 31.79, p < 0.001, respectively). Females showed better attitude score compared to males. Overall KAP were found to be significantly higher (p < 0.001) in middle aged (31–50 years) participants in each group. Participants from urban residents, higher educational background and upper socio-economic class demonstrated significantly greater score in terms of KAP in both nonDM and T2DM groups (p < 0.001). On linear regression analysis, knowledge scores correlated strongly with education, income, residence, diabetic state, BMI and attitude.ConclusionsThe overall level of knowledge and practice concerning diabetes among Bangladeshi population is average, but the overall level of attitude is good both in nonDM and T2DM subjects. To prevent diabetes and its complications there is an urgent need for coordinated educational campaigns with a prioritized focus on poorer, rural and less educated groups.

Polymyxin B and colistin were examined for their ability to inhibit the type II NADH-quinone oxidoreductases (NDH-2) of three species of Gram-negative bacteria. Polymyxin B and colistin inhibited the NDH-2 activity in preparations from all of the isolates in a concentration-dependent manner. The mechanism of NDH-2 inhibition by polymyxin B was investigated in detail with E. coli inner membrane preparations and conformed to a mixed inhibition model with respect to ubiquinone-1 and a non-competitive inhibition model with respect to NADH. These suggest inhibition of vital respiratory enzymes in the bacterial inner membrane represents one of the secondary modes of action for polymyxins.

The dry antibiotic development pipeline coupled with the emergence of multidrug resistant Gram-negative ‘superbugs’ has driven the revival of the polymyxin lipopeptide antibiotics. Polymyxin resistance implies a total lack of antibiotics for the treatment of life-threatening infections. The lack of molecular imaging probes that possess native polymyxin-like antibacterial activity is a barrier to understanding the resistance mechanisms and the development of a new generation of polymyxin lipopeptides. Here we report the regioselective modification of the polymyxin B core scaffold at the N-terminus with the dansyl fluorophore to generate an active probe that mimics polymyxin B pharmacologically. Time-lapse laser scanning confocal microscopy imaging of the penetration of probe (1) into Gram-negative bacterial cells revealed that the probe initially accumulates in the outer membrane and subsequently penetrates into the inner membrane and finally the cytoplasm. The implementation of this polymyxin-mimetic probe will advance the development of platforms for the discovery of novel polymyxin lipopeptides with efficacy against polymyxin-resistant strains.

BackgroundMaternal anaemia is a common problem in pregnancy, particularly in developing countries. The study was aimed at determining the factors associated with anaemia among a group of pregnant mothers who attended an antenatal clinic in Dhaka city.MethodsThis cross-sectional study included 224 pregnant women, who visited the antenatal clinic of the Marie Stops, Dhaka. Demographic data and information on maternal age, gestational age, educational and income level, and socioeconomic status were collected from all the subjects. Haemoglobin status was measured to assess their anaemia. A qualified technician drew venous blood samples from them. The reference values of haemoglobin were categorized according to the World Health Organization (WHO) criteria as follows: normal (11 g/dL or higher), mild (10–10.9 g/dL), and moderate (7–9.9 g/dL). Mild and moderate levels of haemoglobin were defined as anaemic (haemoglobin levels of <11 g/dL). The SPSS software (Windows version 16.0. SPSS Inc, Chicago, USA) was used for analyzing data.ResultsThe mean (±SD) age of the subjects was 26.4 ± 2.81 years. Sixty-three percent of the subjects had normal level of haemoglobin, and 37 % were anaemic 26 % mild and 11 % moderate. Maternal anaemia was significantly associated with age (p = 0.036), education (p = 0.002), income (p = 0.001), living area (p = 0.031). Results of binary logistic regression analysis showed that maternal anaemia was also significantly associated with age (p = 0.006), educational status (primary to 8th grade, p = 0.004; secondary and above, p = 0.002), living area (0.022), and income (0.021).DiscussionA significant proportion of pregnant women were found anaemic. Most data showed education has animpact on awareness to use of health services and iron supplementation should be encouraged to improve the haemoglobin levels in pregnancy.ConclusionsThe results indicate that anaemia is alarmingly high among pregnant women in Dhaka city. Maternal anaemia is associated with age, education level, income level, and living area. The results suggest that pregnant women and members of their families should be urgently educated to understand the importance of antenatal care.

Human anaplastic lymphoma kinase (ALK) has been identified as an oncogene that is mutated or amplified in NBLs. To obtain a better understanding of the molecular events associated with ALK in the pathogenesis of NBL, it is necessary to clarify how ALK gene contributes to NBL progression. In the present study, we found that ALK expression was significantly high in NBL clinical samples with amplified MYCN (n = 126, P < 0.01) and in developing tumors of MYCN-transgenic mice. Indeed, promoter analysis revealed that ALK is a direct transcriptional target of MYCN. Overexpression and knockdown of ALK demonstrated its function in cell proliferation, migration and invasion. Moreover, treatment with an ALK inhibitor, TAE-684, efficiently suppressed such biological effects in MYCN amplified cells and tumor growth of the xenograft in mice. Our present findings explore the fundamental understanding of ALK in order to develop novel therapeutic tools by targeting ALK for aggressive NBL treatment.

The polycomb repressor complex 2 molecule EZH2 is now known to play a role in essential cellular processes, namely, cell fate decisions, cell cycle regulation, senescence, cell differentiation, and cancer development/progression. EZH2 inhibitors have recently been developed; however, their effectiveness and underlying molecular mechanisms in many malignancies have not yet been elucidated in detail. Although the functional role of EZH2 in tumorigenesis in neuroblastoma (NB) has been investigated, mutations of EZH2 have not been reported. A Kaplan–Meier analysis on the event free survival and overall survival of NB patients indicated that the high expression of EZH2 correlated with an unfavorable prognosis. In order to elucidate the functional roles of EZH2 in NB tumorigenesis and its aggressiveness, we knocked down EZH2 in NB cell lines using lentivirus systems. The knockdown of EZH2 significantly induced NB cell differentiation, e.g., neurite extension, and the neuronal differentiation markers, NF68 and GAP43. EZH2 inhibitors also induced NB cell differentiation. We performed a comprehensive transcriptome analysis using Human Gene Expression Microarrays and found that NTRK1 (TrkA) is one of the EZH2-related suppression targets. The depletion of NTRK1 canceled EZH2 knockdown-induced NB cell differentiation. Our integrative methylome, transcriptome, and chromatin immunoprecipitation assays using NB cell lines and clinical samples clarified that the NTRK1 P1 and P2 promoter regions were regulated differently by DNA methylation and EZH2-related histone modifications. The NTRK1 transcript variants 1/2, which were regulated by EZH2-related H3K27me3 modifications at the P1 promoter region, were strongly expressed in favorable, but not unfavorable NB. The depletion and inhibition of EZH2 successfully induced NTRK1 transcripts and functional proteins. Collectively, these results indicate that EZH2 plays important roles in preventing the differentiation of NB cells and also that EZH2-related NTRK1 transcriptional regulation may be the key pathway for NB cell differentiation.

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bIdentifying the pathways involved in the apoptotic cell death that is associated with polymyxin-induced nephrotoxicity is crucial for the development of strategies to ameliorate this dose-limiting side effect and for the development of novel safer polymyxins. The primary aim of this study was to identify the major pathways which lead to polymyxin-induced apoptosis in cultured rat kidney proximal tubular cells (NRK-52E). Caspase-3, -8, and -9 were activated by polymyxin B treatment in a concentrationdependent manner. Concentration-and time-dependent expression of FasL and deformation of mitochondrial morphology were revealed following polymyxin B treatment. The proportion of cells with filamentous mitochondria (regular morphology) following an 8-h treatment with 1.0 mM polymyxin B was 56.2% ؎ 9.7% (n ‫؍‬ 3). This was decreased to 30.7% ؎ 7.5% when the polymyxin B concentration was increased to 2.0 mM. The mitochondrial membrane potential (⌬ m ) decreased to 14.1% ؎ 2.9% in the cells treated with 1.0 mM polymyxin B for 24 h (n ‫؍‬ 3) compared to that in the untreated control group. Concomitantly, concentration-and time-dependent production of mitochondrial superoxide was also observed. This study is the first to have demonstrated that polymyxin-induced apoptosis is mediated through both the death receptor and mitochondrial pathways in cultured renal tubular cells. It provides key information not only for the amelioration of polymyxin-induced nephrotoxicity but also for the discovery of novel safer polymyxin-like antibiotics against Gram-negative "superbugs."