The metabolic syndrome: prevalence, associated factors, and impact on survival among older persons in rural Bangladesh

Objectives

To describe the prevalence of the metabolic syndrome (MetS) among older persons in rural Bangladesh, to investigate whether the prevalence varies by age, sex, literacy, marital status, nutritional status and socio-economic status, and to assess the impact of MetS on survival.

Methods

The study consisted of 456 persons who were aged ≥60 years living in a rural area of Bangladesh during July 2003–March 2004. Data were collected through interview, clinical examination, and laboratory tests, and their survival status until 30^th June 2009 was ascertained through the Matlab surveillance system. We defined MetS following the NCEP ATP III criteria, with minor modifications, i.e., presence of any three of the following: hypertension (BP ≥130/85 mm Hg); random blood glucose (RBG) level ≥7.0 mmol/L; hyper-triglyceridemia (≥2.28 mmol/L); low level of HDL-cholesterol (<1.04 mmol/L for men and <1.29 mmol/L for women); and BMI ≥25.0 kg/m². Data were analysed with logistic regressions for the influential factors of MetS, and with Cox models for the association of MetS with the survival status.

Findings

The overall prevalence of MetS was 19.5%, 20.8% in women, and 18.0% in men. Asset-index and nutritional status were independently associated with MetS. During 4.93 years of follow-up, 18.2% died. In the presence of high RBG, MetS has a significant negative effect on survival (69.4% vs 95.2%, log rank p = 0.02).

Conclusion

This study highlights the importance of the metabolic syndrome in rural Bangladesh. Our findings suggest that there is a need for screening programmes involving the metabolic syndrome to prevent diabetes and cardiovascular diseases.     

Bacterial community diversity in the rhizosphere of nickel hyperaccumulator plant species from Borneo Island (Malaysia)

The Island of Borneo is a major biodiversity hotspot, and in the Malaysian state of Sabah, ultramafic soils are extensive and home to more than 31 endemic nickel hyperaccumulator plants. The aim of this study was to characterize the structure and the diversity of the rhizosphere bacterial communities of several of these nickel hyperaccumulator plants and factors that affect these bacterial communities in Sabah. The most abundant phyla were Proteobacteria, Acidobacteria and Actinobacteria. At family level, Burkholderiaceae and Xanthobacteraceae (Proteobacteria phylum) were the most abundant families in the hyperaccumulator rhizospheres. Redundancy analysis based on soil chemical analyses and relative abundances of the major bacterial phyla showed that abiotic factors of the studied sites drove the bacterial diversity. For all R. aff. bengalensis rhizosphere soil samples, irrespective of studied site, the bacterial diversity was similar. Moreover, the Saprospiraceae family showed a high representativeness in the R. aff. bengalensis rhizosphere soils and was linked with the nickel availability in soils. The ability of R. aff. bengalensis to concentrate nickel in its rhizosphere appears to be the major factor driving the rhizobacterial community diversity unlike for other hyperaccumulator species.     

Ontological model of multi-agent Smart-system for predicting drug properties based on modified algorithms of artificial immune systems

Estimating HIV incidence is crucial for monitoring the epidemiology of this infection, planning screening and intervention campaigns, and evaluating the effectiveness of control measures. However, owing to the long and variable period from HIV infection to the development of AIDS and the introduction of highly active antiretroviral therapy, accurate incidence estimation remains a major challenge. Numerous estimation methods have been proposed in epidemiological modeling studies, and here we review commonly-used methods for estimation of HIV incidence. We review the essential data required for estimation along with the advantages and disadvantages, mathematical structures and likelihood derivations of these methods. The methods include the classical back-calculation method, the method based on CD4+ T-cell depletion, the use of HIV case reporting data, the use of cohort study data, the use of serial or cross-sectional prevalence data, and biomarker approach. By outlining the mechanistic features of each method, we provide guidance for planning incidence estimation efforts, which may depend on national or regional factors as well as the availability of epidemiological or laboratory datasets.     

Characterization of methylglyoxal-modified human IgG by physicochemical methods

Human IgG is a defence protein and quite reactive to dicarbonyls. In this study, methylglyoxal-induced modification of IgG was examined by various biochemical and biophysical methods. The methylglyoxal-induced changes in IgG were monitored by UV-visible and fluorescence spectroscopy, Fourier transform infrared spectroscopy, 1-anilinonaphthalene-8-sulfonic acid (ANS), and thermal denaturation studies. Aggregate formation was studied by Thioflavin T (ThT), Congo red (CR) and scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Spectroscopic studies suggested gross changes in MGO-modified IgG. Fluorogenic AGEs appeared during modification and the MGO-modified IgG gained thermostability. The reaction produced oxidative stress in the medium because carbonyl content increased manifold and sulfhydryl groups decreased. Enhanced binding of the MGO-modified IgG by Congo red and Thioflavin T suggests crosslinking and aggregation. This was supported by SEM and TEM results.     

Docking and molecular dynamics simulation studies on glycation-induced conformational changes of human paraoxonase 1

Human paraoxonase 1 (huPON1) is a calcium-dependent esterase responsible for hydrolysis of a wide variety of substrates including organophosphates, esters, lactones, and paraoxon. Although its natural substrate is unknown, the action of PON as an antioxidant is well documented. Because recent reports have suggested glycation may induce reduced PON activity in diabetes, we investigated the structural features of huPON1 and its glycated mutant by template-based modeling, docking, and molecular dynamics (MD) simulations. Our results corroborated the importance of the His115–His134 dyad in both the lactonase and paraoxonase activity of huPON1. Structural alterations in the glycated model reflected weak interactions between the docked substrate and the active site cleft. We also used MD simulation to gain insight into glycation-induced conformational changes of huPON1 and the implication of this on depleted enzymatic activity. The catalytic calcium found on the surface interacts with the side chain oxygen of residues, including Asn224, Asn270, Asn168, Asp269, and Glu53, and this interaction with the respective residues undergoes minor displacement on glycation. The root-mean-square fluctuation had high motional flexibility in the non-glycated model whereas the conformation of the glycated structure was comparatively stable. Our findings emphasize the consequence of glycation-induced alterations and their effect on overall enzymatic activity.     

Sheep erythrocyte demonstrated better effect than IL-2 and IFN-gamma as biological response modifier against glioma in experimental model

The significant insights into the immunobiology of central nervous system (CNS) and brain tumor have opened up the feasibility of applying 'Immunotherapy' as an alternative to the poor prognosis of malignant brain tumor with conventional therapeutic approaches. Though cytokines like IL-2 and IFN-gamma used against glioma showed some favorable results by eliciting Th1 type immune response, a proper immunotherapeutic agent is still to be searched for. Sheep erythrocyte (SRBC), a corpuscular antigen showed a better therapeutic efficacy in terms of enhanced survival and augmentation of cell mediated immunity (CMI) in a glioma model developed by chemical carcinogen ethyl nitrosourea. Histological findings revealed most efficient glioma rejection in SRBC and combination biological response modifier (BRM) treated groups. Simultaneously E-rosetting, cytotoxicity of lymphocytes, phagocytosis and antigen presenting capacity of myeloid cells established the better therapeutic efficacy of SRBC alone than other BRMs viz. IL-2 and IFN-gamma. Even the effect of combination therapy of different BRMs showed marginal differences in facilitating glioma reduction than the single use of SRBC. These findings emphasized the application of SRBC as an exogenous BRM having the potential as a rational therapeutic adjunct against glioma.     

Three-dimensional model and quaternary structure of the human eye lens protein gamma S-crystallin based on beta- and gamma-crystallin X-ray coordinates and ultracentrifugation.

A 3-dimensional model of the human eye lens protein gamma S-crystallin has been constructed using comparative modeling approaches encoded in the program COMPOSER on the basis of the 3-dimensional structure of gamma-crystallin and beta-crystallin. The model is biased toward the monomeric gamma B-crystallin, which is more similar in sequence. Bovine gamma S-crystallin was shown to be monomeric by analytical ultracentrifugation without any tendency to form assemblies up to concentrations in the millimolar range. The connecting peptide between domains was therefore built assuming an intramolecular association as in the monomeric gamma-crystallins. Because the linker has 1 extra residue compared with gamma B and beta B2, the conformation of the connecting peptide was constructed by using a fragment from a protein database. gamma S-crystallin differs from gamma B-crystallin mainly in the interface region between domains. The charged residues are generally paired, although in a different way from both beta- and gamma-crystallins, and may contribute to the different roles of these proteins in the lens.     

Identification of novel large genomic rearrangements at the BRCA1 locus in Malaysian women with breast cancer

Background: The incidence of breast cancer has been on the rise in Malaysia. It is suggested that a subset of breast cancer cases were associated with germline mutation in breast cancer susceptibility (BRCA) genes. Most of the BRCA mutations reported in Malaysia were point mutations, small deletions and insertions. Here we report the first study of BRCA large genomic rearrangements (LGRs) in Malaysia. We aimed to detect the presence of LGRs in the BRCA genes of Malaysian patients with breast cancer. Methods: Multiplex ligation-dependent probe amplification (MLPA) for BRCA LGRs was carried out on 100 patients (60 were high-risk breast cancer patients previously tested negative/positive for BRCA1 and BRCA2 mutations, and 40 were sporadic breast cancer patients), recruited from three major referral centres, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Hospital Kuala Lumpur (HKL) and Hospital Putrajaya (HPJ). Results: Two novel BRCA1 rearrangements were detected in patients with sporadic breast cancer; both results were confirmed by quantitative PCR. No LGRs were found in patients with high-risk breast cancer. The two large genomic rearrangements detected were genomic amplifications of exon 3 and exon 10. No BRCA2 genomic rearrangement was found in both high-risk and sporadic breast cancer patients. Conclusion: These results will be helpful to understand the mutation spectrum of BRCA1 and BRCA2 genes in Malaysian patients with breast cancer. Further studies involving larger samples are required to establish a genetic screening strategy for both high-risk and sporadic breast cancer patients.     

An oral cancer biobank initiative: a platform for multidisciplinary research in a developing country

Identification of diagnostic markers for early detection and development of novel and therapeutic agents for effective patient management are the main motivation for cancer research. Biological specimens from large cohort and case-control studies which are crucial in providing successful research outcomes are often the limiting factor that hinders research efforts, especially in developing countries. Therefore, the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS) were established to systematically collect large number of samples with comprehensive sociodemographic, clinicopathological, management strategies, quality of life and associated patient follow-up data to facilitate oral cancer research in Malaysia. The MOCDTBS also promotes sharing among researchers and the development of a multidisciplinary research team. The following article aims to describe the process of setting-up and managing the MOCDTBS.     

From clinical and biochemical to molecular genetic diagnosis of Wilson disease in Latvia

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism characterized by hepatic and/or neurological damage. More than 300 mutations in gene ATP7B causing this defect have been reported. The data on correlation between WD patient genotypes and clinical presentation are controversial. In this paper, the results of ATP7B mutation analysis by testing for mutation H1069Q and direct sequencing of six exons together with the clinical data of 40 Latvian WD patients are presented. Two previously described and two novel mutations as well as one previously reported polymorphism were identified. The H1069Q mutation was present at 52.5% of the disease alleles. One individual among 157 healthy Latvians was also found to be a mutation H1069Q carrier. The estimated incidence of WD in Latvia is ∼1 in 25600. Wide clinical variability was observed among individuals with the same ATP7B genotype, thus supporting the suggestion that modifying factors play an additional role in the pathogenesis of WD. An algorithm for the diagnosis of WD, including testing for mutation H1069Q, is recommended for the populations where mutation H1069Q accounts for 50% of WD alleles or more. The text was submitted authors English.