A prospective cohort study of dietary patterns of non-western migrants in the Netherlands in relation to risk factors for cardiovascular diseases: HELIUS-Dietary Patterns

<p>Abstract</p> <p>Background</p> <p>In Western countries the prevalence of cardiovascular disease (CVD) is often higher in non-Western migrants as compared to the host population. Diet is an important modifiable determinant of CVD. Increasingly, dietary patterns rather than single nutrients are the focus of research in an attempt to account for the complexity of nutrient interactions in foods. Research on dietary patterns in non-Western migrants is limited and may be hampered by a lack of validated instruments that can be used to assess the habitual diet of non-western migrants in large scale epidemiological studies. The ultimate aims of this study are to (1) understand whether differences in dietary patterns explain differences in CVD risk between ethnic groups, by developing and validating ethnic-specific Food Frequency Questionnaires (FFQs), and (2) to investigate the determinants of these dietary patterns. This paper outlines the design and methods used in the HELIUS-Dietary Patterns study and describes a systematic approach to overcome difficulties in the assessment and analysis of dietary intake data in ethnically diverse populations.</p> <p>Methods/Design</p> <p>The HELIUS-Dietary Patterns study is embedded in the HELIUS study, a Dutch multi-ethnic cohort study. After developing ethnic-specific FFQs, we will gather data on the habitual intake of 5000 participants (18-70 years old) of ethnic Dutch, Surinamese of African and of South Asian origin, Turkish or Moroccan origin. Dietary patterns will be derived using factor analysis, but we will also evaluate diet quality using hypothesis-driven approaches. The relation between dietary patterns and CVD risk factors will be analysed using multiple linear regression analysis. Potential underlying determinants of dietary patterns like migration history, acculturation, socio-economic factors and lifestyle, will be considered.</p> <p>Discussion</p> <p>This study will allow us to investigate the contribution of the dietary patterns on CVD risk factors in a multi-ethnic population. Inclusion of five ethnic groups residing in one setting makes this study highly innovative as confounding by local environment characteristics is limited. Heterogeneity in the study population will provide variance in dietary patterns which is a great advantage when studying the link between diet and disease.</p

BRIT1/MCPH1 Is Essential for Mitotic and Meiotic Recombination DNA Repair and Maintaining Genomic Stability in Mice

BRIT1 protein (also known as MCPH1) contains 3 BRCT domains which are conserved in BRCA1, BRCA2, and other important molecules involved in DNA damage signaling, DNA repair, and tumor suppression. BRIT1 mutations or aberrant expression are found in primary microcephaly patients as well as in cancer patients. Recent in vitro studies suggest that BRIT1/MCPH1 functions as a novel key regulator in the DNA damage response pathways. To investigate its physiological role and dissect the underlying mechanisms, we generated BRIT1−/− mice and identified its essential roles in mitotic and meiotic recombination DNA repair and in maintaining genomic stability. Both BRIT1−/− mice and mouse embryonic fibroblasts (MEFs) were hypersensitive to γ-irradiation. BRIT1−/− MEFs and T lymphocytes exhibited severe chromatid breaks and reduced RAD51 foci formation after irradiation. Notably, BRIT1−/− mice were infertile and meiotic homologous recombination was impaired. BRIT1-deficient spermatocytes exhibited a failure of chromosomal synapsis, and meiosis was arrested at late zygotene of prophase I accompanied by apoptosis. In mutant spermatocytes, DNA double-strand breaks (DSBs) were formed, but localization of RAD51 or BRCA2 to meiotic chromosomes was severely impaired. In addition, we found that BRIT1 could bind to RAD51/BRCA2 complexes and that, in the absence of BRIT1, recruitment of RAD51 and BRCA2 to chromatin was reduced while their protein levels were not altered, indicating that BRIT1 is involved in mediating recruitment of RAD51/BRCA2 to the damage site. Collectively, our BRIT1-null mouse model demonstrates that BRIT1 is essential for maintaining genomic stability in vivo to protect the hosts from both programmed and irradiation-induced DNA damages, and its depletion causes a failure in both mitotic and meiotic recombination DNA repair via impairing RAD51/BRCA2's function and as a result leads to infertility and genomic instability in mice

Natural History of Tuberculosis: Duration and Fatality of Untreated Pulmonary Tuberculosis in HIV Negative Patients: A Systematic Review

Background The prognosis, specifically the case fatality and duration, of untreated tuberculosis is important as many patients are not correctly diagnosed and therefore receive inadequate or no treatment. Furthermore, duration and case fatality of tuberculosis are key parameters in interpreting epidemiological data. Methodology and Principal Findings To estimate the duration and case fatality of untreated pulmonary tuberculosis in HIV negative patients we reviewed studies from the pre-chemotherapy era. Untreated smear-positive tuberculosis among HIV negative individuals has a 10-year case fatality variously reported between 53% and 86%, with a weighted mean of 70%. Ten-year case fatality of culture-positive smear-negative tuberculosis was nowhere reported directly but can be indirectly estimated to be approximately 20%. The duration of tuberculosis from onset to cure or death is approximately 3 years and appears to be similar for smear-positive and smear-negative tuberculosis. Conclusions Current models of untreated tuberculosis that assume a total duration of 2 years until self-cure or death underestimate the duration of disease by about one year, but their case fatality estimates of 70% for smear-positive and 20% for culture-positive smear-negative tuberculosis appear to be satisfactory

Microbiology of destructive periodontal disease in adolescent patients with congenital neutropenia - A report of 3 cases

Background, aims: Congenital neutropenia is one condition that may predispose for destructive periodontal disease at a young age. In this report, we describe the microbiology of 3 adolescent patients with congenital neutropenia two of whom suffered from severe periodontitis. Method: Microbiological testing of the parents was also performed in 1 case. DNA fingerprinting was used to study transmission of putative periodontal pathogens in this case. From 1 patient with periodontitis, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were isolated; a 2nd periodontitis patient was infected with P. gingivalis. A 3rd patient had gingivitis only and no A. actinomycetemcomitans or P. gingivalis were found. Results: Using the amplified fragment length polymorphism DNA fingerprinting technique, bacterial transmission between the father and a patient was shown for A. actinomycetemcomitans but not for P. gingivalis