Early MicroRNA expression profile as a prognostic biomarker for the development of pelvic inflammatory disease in a mouse model of chlamydial genital infection

It is not currently possible to predict the probability of whether a woman with a chlamydial genital infection will develop pelvic inflammatory disease (PID). To determine if specific biomarkers may be associated with distinct chlamydial pathotypes, we utilized two Chlamydia muridarum variants (C. muridarum Var001 [CmVar001] and CmVar004) that differ in their abilities to elicit upper genital tract pathology in a mouse model. CmVar004 has a lower growth rate in vitro and induces pathology in only 20% of C57BL/6 mouse oviducts versus 83.3% of oviducts in CmVar001-infected mice. To determine if chemokine and cytokine production within 24 h of infection is associated with the outcome of pathology, levels of 15 chemokines and cytokines were measured. CmVar004 infection induced significantly lower levels of CXCL1, CXCL2, tumor necrosis factor alpha (TNF-α), and CCL2 in comparison to CmVar001 infection with similar rRNA (rs16) levels for Chlamydiae. A combination of microRNA (miRNA) sequencing and quantitative real-time PCR (qRT-PCR) analysis of 134 inflammation-related miRNAs was performed 24 h postinfection to determine if the chemokine/cytokine responses would also be reflected in miRNA expression profiles. Interestingly, 12 miRNAs (miR-135a-5p, miR298-5p, miR142-3p, miR223-3p, miR299a-3p, miR147-3p, miR105, miR325-3p, miR132-3p, miR142-5p, miR155-5p, and miR-410-3p) were overexpressed during CmVar004 infection compared to CmVar001 infection, inversely correlating with the respective chemokine/cytokine responses. To our knowledge, this is the first report demonstrating that early biomarkers elicited in the host can differentiate between two pathological variants of chlamydiae and be predictive of upper tract disease. © 2014 Yeruva et al

Parents’ experiences of health visiting for children with Down syndrome

© MA Healthcare Limited.Children with Down syndrome have an increased likelihoodof experiencing serious health conditions. Health visitors canhave an important role in monitoring and promoting healthand development for young children with Down syndrome.This study aimed to explore parents’ experiences of healthvisiting services for children with Down syndrome. Twentyfour parents of children with Down syndrome aged 0–5 yearscompleted a brief questionnaire about the number and natureof visits from health visitors in the previous 12 months andtheir support needs. Some parents commented that otherprofessionals met the needs of their child, whereas others saidthat they would like more advice and support from healthvisitors. A further exploration of broader health serviceprovision, including health visiting, for young children withDown syndrome is needed.Peer reviewedFinal Accepted Versio

Time to Update and Quantitative Changes in the Results of Cochrane Pregnancy and Childbirth Reviews

BACKGROUND: The recommended interval between updates for systematic reviews included in The Cochrane Library is 2 years. However, it is unclear whether this interval is always appropriate. Whereas excessive updating wastes time and resources, insufficient updating allows out-of-date or incomplete evidence to guide clinical decision-making. We set out to determine, for Cochrane pregnancy and childbirth reviews, the frequency of updates, factors associated with updating, and whether updating frequency was appropriate. METHODOLOGY/PRINCIPAL FINDINGS: Cochrane pregnancy and childbirth reviews published in Issue 3, 2007 of the Cochrane Database of Systematic Reviews were retrieved, and data were collected from their original and updated versions. Quantitative changes were determined for one of the primary outcomes (mortality, or the outcome of greatest clinical significance). Potential factors associated with time to update were assessed using the Cox proportional hazard model. Among the 101 reviews in our final sample, the median time before the first update was 3.3 years (95% CI 2.7-3.8). Only 32.7% had been updated within the recommended interval of 2 years. In 75.3% (76/101), a median of 3 new trials with a median of 576 additional participants were included in the updated versions. There were quantitative changes in 71% of the reviews that included new trials (54/76): the median change in effect size was 18.2%, and the median change in 95% CI width was 30.8%. Statistical significance changed in 18.5% (10/54) of these reviews, but conclusions were revised in only 3.7% (2/54). A shorter time to update was associated with the same original review team at updating. CONCLUSIONS/SIGNIFICANCE: Most reviews were updated less frequently than recommended by Cochrane policy, but few updates had revised conclusions. Prescribed time to update should be reconsidered to support improved decision-making while making efficient use of limited resources

Magnesium intake and colorectal cancer risk in the Netherlands Cohort Study

Energy-adjusted magnesium intake was nonsignificantly inversely related to risk of colorectal cancer (n=2328) in the Netherlands Cohort Study on Diet and Cancer that started in 1986 (n=58 279 men and 62 573 women). Statistically significant inverse trends in risk were observed in overweight subjects for colon and proximal colon cancer across increasing quintiles of magnesium uptake (P-trend, 0.05 and 0.02, respectively). Although an overall protective effect was not afforded, our results suggest an effect of magnesium in overweight subjects, possibly through decreasing insulin resistance

Trend-TDT – a transmission/disequilibrium based association test on functional mini/microsatellites

<p>Abstract</p> <p>Background</p> <p>Minisatellites and microsatellites are associated with human disease, not only as markers of risk but also involved directly in disease pathogenesis. They may play significant roles in replication, repair and mutation of DNA, regulation of gene transcription and protein structure alteration. Phenotypes can thus be affected by mini/microsatellites in a manner proportional to the length of the allele. Here we propose a new method to assess the linear trend toward transmission of shorter or longer alleles from heterozygote parents to affected child.</p> <p>Results</p> <p>This test (trend-TDT) performs better than other TDT (Transmission/Disequilibrium Test) type tests, such as TDT_maxand TDT_L/S, under most marker-disease association models.</p> <p>Conclusion</p> <p>The trend-TDT test is a more powerful association test when there is a biological basis to suspect a relationship between allele length and disease risk.</p

Dairy consumption and ovarian cancer risk in the Netherlands Cohort Study on Diet and Cancer

Ovary cancer risk in relation to consumption of dairy products was investigated using a self-administered questionnaire on dietary habits and other risk factors for cancer, which was completed in 1986 by 62 573 postmenopausal women participating in the Netherlands Cohort Study. Follow-up for cancer was implemented by annual record linkage with the Netherlands Cancer Registry and a nationwide pathology registry. After 11.3 years of follow-up, data of 252 incident epithelial ovarian cancer cases and 2216 subcohort members were available for analysis. No association was seen between consumption of milk, yoghurt, cheese or fermented dairy products and ovarian cancer risk. The multivariable adjusted relative risk of epithelial ovarian cancer for women in the highest compared to the lowest quintile of intake of lactose or dairy fat was 0.93 (95% confidence interval (CI)=0.60–1.45; Ptrend=0.32) and 1.53 (95% CI=1.00–2.36; Ptrend=0.11), respectively. Lactose or dairy fat intakes were not associated with serous ovarian cancer risk. Our results do not support an association between consumption of dairy products or lactose intake and ovarian cancer

Accelerating Policy Decisions to Adopt Haemophilus influenzae Type b Vaccine: A Global, Multivariable Analysis

Jessica Shearer and colleagues analyze data from 147 countries to identify factors that influence the time taken to introduce routine vaccination against Haemophilus influenzae type b (Hib)

Exposure to Non-Steroidal Anti-Inflammatory Drugs during Pregnancy and the Risk of Selected Birth Defects: A Prospective Cohort Study

Contains fulltext : 97906.pdf (publisher's version ) (Open Access)BACKGROUND: Since use of non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy is common, small increases in the risk of birth defects may have significant implications for public health. Results of human studies on the teratogenic risks of NSAIDs are inconsistent. Therefore, we evaluated the risk of selected birth defects after prenatal exposure to prescribed and over-the-counter NSAIDs. METHODS AND FINDINGS: We used data on 69,929 women enrolled in the Norwegian Mother and Child Cohort Study between 1999 and 2006. Data on NSAID exposure were available from a self-administered questionnaire completed around gestational week 17. Information on pregnancy outcome was obtained from the Medical Birth Registry of Norway. Only birth defects suspected to be associated with NSAID exposure based upon proposed teratogenic mechanisms and previous studies were included in the multivariable logistic regression analyses. A total of 3,023 women used NSAIDs in gestational weeks 0-12 and 64,074 women did not report NSAID use in early pregnancy. No associations were observed between overall exposure to NSAIDs during pregnancy and the selected birth defects separately or as a group (adjusted odds ratio 0.7, 95% confidence interval 0.4-1.1). Associations between maternal use of specific types of NSAIDs and the selected birth defects were not found either, although an increased risk was seen for septal defects and exposure to multiple NSAIDs based on small numbers (2 exposed cases; crude odds ratio 3.9, 95% confidence interval 0.9-15.7). CONCLUSIONS: Exposure to NSAIDs during the first 12 weeks of gestation does not seem to be associated with an increased risk of the selected birth defects. However, due to the small numbers of NSAID-exposed infants for the individual birth defect categories, increases in the risks of specific birth defects could not be excluded

Delay to celiac disease diagnosis and its implications for health-related quality of life

<p>Abstract</p> <p>Background</p> <p>To determine how the delay in diagnosing celiac disease (CD) has developed during recent decades and how this affects the burden of disease in terms of health-related quality of life (HRQoL), and also to consider differences with respect to sex and age.</p> <p>Methods</p> <p>In collaboration with the Swedish Society for Coeliacs, a questionnaire was sent to 1,560 randomly selected members, divided in equal-sized age- and sex strata, and 1,031 (66%) responded. HRQoL was measured with the EQ-5D descriptive system and was then translated to quality-adjusted life year (QALY) scores. A general population survey was used as comparison.</p> <p>Results</p> <p>The mean delay to diagnosis from the first symptoms was 9.7 years, and from the first doctor visit it was 5.8 years. The delay has been reduced over time for some age groups, but is still quite long. The mean QALY score during the year prior to initiated treatment was 0.66; it improved after diagnosis and treatment to 0.86, and was then better than that of a general population (0.79).</p> <p>Conclusions</p> <p>The delay from first symptoms to CD diagnosis is unacceptably long for many persons. Untreated CD results in poor HRQoL, which improves to the level of the general population if diagnosed and treated. By shortening the diagnostic delay it is possible to reduce this unnecessary burden of disease. Increased awareness of CD as a common health problem is needed, and active case finding should be intensified. Mass screening for CD might be an option in the future.</p

Expression of yeast lipid phosphatase Sac1p is regulated by phosphatidylinositol-4-phosphate

<p>Abstract</p> <p>Background</p> <p>Phosphoinositides play a central role in regulating processes at intracellular membranes. In yeast, a large number of phospholipid biosynthetic enzymes use a common mechanism for transcriptional regulation. Yet, how the expression of genes encoding lipid kinases and phosphatases is regulated remains unknown.</p> <p>Results</p> <p>Here we show that the expression of lipid phosphatase Sac1p in the yeast <it>Saccharomyces cerevisiae </it>is regulated in response to changes in phosphatidylinositol-4-phosphate (PI(4)P) concentrations. Unlike genes encoding enzymes involved in phospholipid biosynthesis, expression of the <it>SAC1 </it>gene is independent of inositol levels. We identified a novel 9-bp motif within the 5' untranslated region (5'-UTR) of <it>SAC1 </it>that is responsible for PI(4)P-mediated regulation. Upregulation of <it>SAC1 </it>promoter activity correlates with elevated levels of Sac1 protein levels.</p> <p>Conclusion</p> <p>Regulation of Sac1p expression via the concentration of its major substrate PI(4)P ensures proper maintenance of compartment-specific pools of PI(4)P.</p