Dupuytren's disease in bosnia and herzegovina. An epidemiological study

BACKGROUND: It is generally held that Dupuytren's disease is more common in northern than in southern Europe, but there are very few studies from southern European countries. METHODS: We examined the hands of 1207 men and women over the age of 50 years in Bosnia and Herzegovina. RESULTS: The prevalence of Dupuytren's disease was highly age-dependent, ranging from 17% for men between 50–59 years to 60% in the oldest men. The prevalence among women was lower. The great majority only had palmar changes without contracture of the digit. The prevalence was significantly lower among Bosnian Muslim men than among Bosnian Croat and Serbian men and significantly increased among diabetics. No association could be detected between Dupuytren's disease and smoking, alcohol consumption or living in rural or urban areas. CONCLUSION: We conclude that, contrary to previous opinion, Dupuytren's disease is common in Bosnia and Herzegovina

Improved Culture Medium (TiKa) for Mycobacterium avium Subspecies Paratuberculosis (MAP) Matches qPCR Sensitivity and Reveals Significant Proportions of Non-viable MAP in Lymphoid Tissue of Vaccinated MAP Challenged Animals.

The quantitative detection of viable pathogen load is an important tool in determining the degree of infection in animals and contamination of foodstuffs. Current conventional culture methods are limited in their ability to determine these levels in Mycobacterium avium subspecies paratuberculosis (MAP) due to slow growth, clumping and low recoverability issues. The principle goal of this study was to evaluate a novel culturing process (TiKa) with unique ability to stimulate MAP growth from low sample loads and dilutions. We demonstrate it was able to stimulate a mean 29-fold increase in recoverability and an improved sensitivity of up to three logs when compared with conventional culture. Using TiKa culture, MAP clumping was minimal and produced visible colonies in half the time required by standard culture methods. Parallel quantitative evaluation of the TiKa culture approach and qPCR on MAP loads in tissue and gut mucosal samples from a MAP vaccine-challenge study, showed good correlations between colony counts (cfu) and qPCR derived genome equivalents (Geq) over a large range of loads with a 30% greater sensitivity for TiKa culture approach at low loads (two logs). Furthermore, the relative fold changes in Geq and cfu from the TiKa culture approach suggests that non-mucosal tissue loads from MAP infected animals contained a reduced proportion of non-viable MAP (mean 19-fold) which was reduced significantly further (mean 190-fold) in vaccinated "reactor" calves. This study shows TiKa culture equates well with qPCR and provides important evidence that accuracy in estimating viable MAP load using DNA tests alone may vary significantly between samples of mucosal and lymphatic origin

How DNA Barcodes Complement Taxonomy and Explore Species Diversity: The Case Study of a Poorly Understood Marine Fauna

BACKGROUND: The species boundaries of some venerids are difficult to define based solely on morphological features due to their indistinct intra- and interspecific phenotypic variability. An unprecedented biodiversity crisis caused by human activities has emerged. Thus, to access the biological diversity and further the conservation of this taxonomically muddling bivalve group, a fast and simple approach that can efficiently examine species boundaries and highlight areas of unrecognized diversity is urgently needed. DNA barcoding has proved its effectiveness in high-volume species identification and discovery. In the present study, Chinese fauna was chosen to examine whether this molecular biomarker is sensitive enough for species delimitation, and how it complements taxonomy and explores species diversity. METHODOLOGY/PRINCIPAL FINDINGS: A total of 315 specimens from around 60 venerid species were included, qualifying the present study as the first major analysis of DNA barcoding for marine bivalves. Nearly all individuals identified to species level based on morphological traits possessed distinct barcode clusters, except for the specimens of one species pair. Among the 26 individuals that were not assigned binomial names a priori, twelve respectively nested within a species genealogy. The remaining individuals formed five monophyletic clusters that potentially represent species new to science or at least unreported in China. Five putative hidden species were also uncovered in traditional morphospecies. CONCLUSIONS/SIGNIFICANCE: The present study shows that DNA barcoding is effective in species delimitation and can aid taxonomists by indicating useful diagnostic morphological traits, informing needful revision, and flagging unseen species. Moreover, the BOLD system, which deposits barcodes, morphological, geographical and other data, has the potential as a convenient taxonomic platform

Influence of advanced age of maternal grandmothers on Down syndrome

BACKGROUND: Down syndrome (DS) is the most common chromosomal anomaly associated with mental retardation. This is due to the occurrence of free trisomy 21 (92–95%), mosaic trisomy 21 (2–4%) and translocation (3–4%). Advanced maternal age is a well documented risk factor for maternal meiotic nondisjunction. In India three children with DS are born every hour and more DS children are given birth to by young age mothers than by advanced age mothers. Therefore, detailed analysis of the families with DS is needed to find out other possible causative factors for nondisjunction. METHODS: We investigated 69 families of cytogenetically confirmed DS children and constructed pedigrees of these families. We also studied 200 randomly selected families belonging to different religions as controls. Statistical analysis was carried out using logistic regression. RESULTS: Out of the 69 DS cases studied, 67 were free trisomy 21, two cases were mosaic trisomy 21 and there were none with translocation. The number of DS births was greater for the young age mothers compared with the advanced age mothers. It has also been recorded that young age mothers (18 to 29 years) born to their mothers at the age 30 years and above produced as high as 91.3% of children with DS. The logistic regression of case- control study of DS children revealed that the odds ratio of age of grandmother was significant when all the four variables were used once at a time. However, the effect of age of mother and father was smaller than the effect of age of maternal grandmother. Therefore, for every year of advancement of age of the maternal grandmother, the risk (odds) of birth of DS baby increases by 30%. CONCLUSION: Besides the known risk factors, mother's age, father's age, the age of the maternal grandmother at the time of birth of the mother is a risk factor for the occurrence of Down syndrome

CpG-Methylation Regulates a Class of Epstein-Barr Virus Promoters

DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian gene regulation. In general, cytosine-phosphatidyl-guanosine (CpG)-methylated promoters are transcriptionally repressed and nuclear proteins such as MECP2, MBD1, MBD2, and MBD4 bind CpG-methylated DNA and contribute to epigenetic silencing. Methylation of viral DNA also regulates gene expression of Epstein-Barr virus (EBV), which is a model of herpes virus latency. In latently infected human B cells, the viral DNA is CpG-methylated, the majority of viral genes is repressed and virus synthesis is therefore abrogated. EBV's BZLF1 encodes a transcription factor of the AP-1 family (Zta) and is the master gene to overcome viral gene repression. In a genome-wide screen, we now identify and characterize those viral genes, which Zta regulates. Among them are genes essential for EBV's lytic phase, which paradoxically depend on strictly CpG-methylated promoters for their Zta-induced expression. We identified novel DNA recognition motifs, termed meZRE (methyl-Zta-responsive element), which Zta selectively binds in order to ‘read’ DNA in a methylation- and sequence-dependent manner unlike any other known protein. Zta is a homodimer but its binding characteristics to meZREs suggest a sequential, non-palindromic and bipartite DNA recognition element, which confers superior DNA binding compared to CpG-free ZREs. Our findings indicate that Zta has evolved to transactivate cytosine-methylated, hence repressed, silent promoters as a rule to overcome epigenetic silencing

HOXB4 Gene Expression Is Regulated by CDX2 in Intestinal Epithelial Cells

The mammalian Caudal-related homeobox transcription factor 2 (CDX2) plays a key role in the homeobox regulatory network and is essential in regulating the expression of several homeobox (HOX) genes during embryonic development, particularly in the gut. Genome-wide CDX2 chromatin immunoprecipitation analysis and expression data from Caco2 cells also suggests a role for CDX2 in the regulation of HOXB4 gene expression in the intestinal epithelium. Thus, the aim of this study was to investigate whether HOXB4 gene expression is regulated by CDX2 in the intestinal epithelium. We demonstrated binding of CDX2 to four different CDX2 binding sites in an enhancer region located upstream of the HOXB4 transcription start site. Mutations in the CDX2 binding sites reduced HOXB4 gene activity, and knock down of endogenous CDX2 expression by shRNA reduced HOXB4 gene expression. This is the first report demonstrating the CDX2 regulation of HOXB4 gene expression in the developed intestinal epithelium, indicating a possible role for HOXB4 in intestinal homeostasis

Metabolic Effects Associated with ICS in Patients with COPD and Comorbid Type 2 Diabetes: A Historical Matched Cohort Study

Background Management guidelines for chronic obstructive pulmonary disease (COPD) recommend that inhaled corticosteroids (ICS) are prescribed to patients with the most severe symptoms. However, these guidelines have not been widely implemented by physicians, leading to widespread use of ICS in patients with mild-to-moderate COPD. Of particular concern is the potential risk of worsening diabetic control associated with ICS use. Here we investigate whether ICS therapy in patients with COPD and comorbid type 2 diabetes mellitus (T2DM) has a negative impact on diabetic control, and whether these negative effects are dose-dependent. Methods and Findings This was a historical matched cohort study utilising primary care medical record data from two large UK databases. We selected patients aged >= 40 years with COPD and T2DM, prescribed ICS (n = 1360) or non-ICS therapy (n = 2642) between 2008 and 2012. The primary endpoint was change in HbA(1c) between the baseline and outcome periods. After 1:1 matching, each cohort consisted of 682 patients. Over the 12-18-month outcome period, patients prescribed ICS had significantly greater increases in HbA1c values compared with those prescribed non-ICS therapies; adjusted difference 0.16% (95% confidence interval [Cl]: 0.05-0.27%) in all COPD patients, and 0.25% (95% Cl: 0.10-0.40%) in mild-to-moderate COPD patients. Patients in the ICS cohort also had significantly more diabetes-related general practice visits per year and received more frequent glucose strip prescriptions, compared with those prescribed non-ICS therapies. Patients prescribed higher cumulative doses of ICS (> 250 mg) had greater odds of increased HbA(1c) and/or receiving additional antidiabetic medication, and increased odds of being above the Quality and Outcomes Framework (QOF) target for HbA1c levels, compared with those prescribed lower cumulative doses ( Conclusion For patients with COPD and comorbid T2DM, ICS therapy may have a negative impact on diabetes control. Patients prescribed higher cumulative doses of ICS may be at greater risk of diabetes progression