Short-Term Serial Sampling of Natriuretic Peptides in Patients Presenting With Chest Pain

ObjectivesThe purpose of this study was to characterize the diagnostic and prognostic utility of short-term dynamic changes in natriuretic peptides in patients presenting with chest pain.BackgroundAlthough single levels of natriuretic peptides in patients admitted for acute coronary syndromes (ACS) have important prognostic value, it is unclear whether serial sampling of natriuretic peptides might have both diagnostic and prognostic value in the setting of chest pain.MethodsWe followed 276 patients for 90 days who presented to the emergency department with chest pain. We sampled brain natriuretic peptide (BNP) and amino-terminal (NT)-proBNP up to 5 times within 24 h of presentation and again at discharge. Follow-up data was collected at 30 and 90 days after admission. Adverse events included emergency department visits for chest pain, cardiac readmission, and death. We assessed the prognostic and diagnostic value of baseline natriuretic peptide measurements with receiver-operating characteristic analyses.ResultsNatriuretic peptides were diagnostic for congestive heart failure (CHF) and new-onset CHF but less so for ACS. The prognostic utility of serial sampling was evaluated through testing the statistical contribution of each future time point (as well as variability over time) over and above the baseline values in logistic regression models.ConclusionsBaseline elevated BNP and NT-proBNP concentrations were predictive of adverse events at 30 and 90 days. Serial sampling did not improve the prognostic value of BNP or NT-proBNP

Mapping genomic and transcriptomic alterations spatially in epithelial cells adjacent to human breast carcinoma.

Almost all genomic studies of breast cancer have focused on well-established tumours because it is technically challenging to study the earliest mutational events occurring in human breast epithelial cells. To address this we created a unique dataset of epithelial samples ductoscopically obtained from ducts leading to breast carcinomas and matched samples from ducts on the opposite side of the nipple. Here, we demonstrate that perturbations in mRNA abundance, with increasing proximity to tumour, cannot be explained by copy number aberrations. Rather, we find a possibility of field cancerization surrounding the primary tumour by constructing a classifier that evaluates where epithelial samples were obtained relative to a tumour (cross-validated micro-averaged AUC = 0.74). We implement a spectral co-clustering algorithm to define biclusters. Relating to over-represented bicluster pathways, we further validate two genes with tissue microarrays and in vitro experiments. We highlight evidence suggesting that bicluster perturbation occurs early in tumour development

The Effect of Cataract on Color Vision Measurement with the Low-Vision Cambridge Colour Test

Purpose: To quantify the effect of cataract on colour vision as measured by the low vision Cambridge Colour Test (lvCCT). A secondary aim of our study was to understand whether different types and severities of cataract have different effects on colour vision. Design: Cohort study Subjects: Patients aged 18 - 95 years attending for routine cataract surgery at the Oxford Eye Hospital. Methods: The lvCCT was performed to measure colour sensitivity in both eyes in a cohort of patients undergoing routine cataract surgery both pre-operatively and post-operatively. The crystalline lens was examined and graded according to the Lens Opacities Classification System III (LOCS III) to determine the type and severity of cataract. Measures of repeatability were performed for the data to explore test-retest bias using Bland-Altman analysis. The Wilcoxon signed-rank test was performed to assess the effect of cataract on colour vision by comparing control and surgical test measurements. Three multiple linear regressions were performed to relate cataract grading or severity to colour vision measurements. Main outcome measures: Colour discrimination along each of the protan, deutan, and tritan confusion lines. Results: The Wilcoxon signed-rank test showed a statistically significant difference in both the protan (P=0.024) and tritan (P=0.020) axes upon comparison of control and surgical test measurements. As severity of cataract increased colour vision sensitivity was more greatly affected, and nuclear sclerotic cataract had the most profound effect upon colour vision sensitivity in the lvCCT. The linear regression models though showed these observations did not reach statistical significance. Conclusions: Cataract surgery has a statistically significant effect upon colour vision in both the protan and tritan axes. The effects of specific subtypes of cataract and different severities could not be elucidated due to the high prevalence of patients presenting with mixed cataract. LvCCT colour sensitivity measurements are regularly used as outcome measures in clinical gene therapy trials involving vitreoretinal surgery, and vitrectomy accelerates cataract formation. Therefore, it is important to quantify the effect of cataract upon colour vision measurements so it may be taken into account when used as an outcome measure in clinical trials. We were unable to derive a precise correction factor for cataract on color vision measurements

DNA replication stress restricts ribosomal DNA copy number

Ribosomal RNAs (rRNAs) in budding yeast are encoded by ~100–200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA) locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how “normal” copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen a yeast conditional temperature-sensitive mutant collection of essential genes. Our screen revealed that low rDNA copy number is associated with compromised DNA replication. Further, subculturing yeast under two separate conditions of DNA replication stress selected for a contraction of the rDNA array independent of the replication fork blocking protein, Fob1. Interestingly, cells with a contracted array grew better than their counterparts with normal copy number under conditions of DNA replication stress. Our data indicate that DNA replication stresses select for a smaller rDNA array. We speculate that this liberates scarce replication factors for use by the rest of the genome, which in turn helps cells complete DNA replication and continue to propagate. Interestingly, tumors from mini chromosome maintenance 2 (MCM2)-deficient mice also show a loss of rDNA repeats. Our data suggest that a reduction in rDNA copy number may indicate a history of DNA replication stress, and that rDNA array size could serve as a diagnostic marker for replication stress. Taken together, these data begin to suggest the selective pressures that combine to yield a “normal” rDNA copy number

Antecedent Avian Immunity Limits Tangential Transmission of West Nile Virus to Humans

Background: West Nile virus (WNV) is a mosquito-borne flavivirus maintained and amplified among birds and tangentially transmitted to humans and horses which may develop terminal neuroinvasive disease. Outbreaks typically have a three-year pattern of silent introduction, rapid amplification and subsidence, followed by intermittent recrudescence. Our hypothesis that amplification to outbreak levels is contingent upon antecedent seroprevalence within maintenance host populations was tested by tracking WNV transmission in Los Angeles, California from 2003 through 2011. Methods: Prevalence of antibodies against WNV was monitored weekly in House Finches and House Sparrows. Tangential or spillover transmission was measured by seroconversions in sentinel chickens and by the number of West Nile neuroinvasive disease (WNND) cases reported to the Los Angeles County Department of Public Health. Results: Elevated seroprevalence in these avian populations was associated with the subsidence of outbreaks and in the antecedent dampening of amplification during succeeding years. Dilution of seroprevalence by recruitment resulted in the progressive loss of herd immunity following the 2004 outbreak, leading to recrudescence during 2008 and 2011. WNV appeared to be a significant cause of death in these avian species, because the survivorship of antibody positive birds significantly exceeded that of antibody negative birds. Cross-correlation analysis showed that seroprevalence was negatively correlated prior to the onset of human cases and then positively correlated, peaking at 4–6 weeks after the onse

The places parents go: understanding the breadth, scope, and experiences of activity spaces for parents

The final publication is available at Springer via https://doi.org/10.1007/s10708-015-9690-yNeighborhood environments are related to parenting behaviors, which in turn have a life-long effect on children’s health and well-being. Activity spaces, which measure individual routine patterns of movement, may be helpful in assessing how physical and social environments shape parenting. In this study we use qualitative data and GIS mapping from four California cities to examine parental activity spaces. Parents described a number of factors that shape their activity spaces including caregiving status, the age of their children, and income. Parental activity spaces also varied between times (weekends vs. weekdays) and places (adult-only vs. child-specific places). Knowing how to best capture and study parental activity spaces could identify mechanisms by which environmental factors influence parenting behaviors and child health

Erratum: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls.

This corrects the article DOI: 10.1038/sdata.2017.179

Clinically relevant safety issues associated with St. John's wort product labels

<p>Abstract</p> <p>Background</p> <p>St. John's wort (SJW), used to treat depression, is popular in the USA, Canada, and parts of Europe. However, there are documented interactions between SJW and prescription medications including warfarin, cyclosporine, indinavir, and oral contraceptives. One source of information about these safety considerations is the product label. The aim of this study was to evaluate the clinically relevant safety information included on labeling in a nationally representative sample of SJW products from the USA.</p> <p>Methods</p> <p>Eight clinically relevant safety issues were identified: drug interactions (SJW-HIV medications, SJW-immunosupressants, SJW-oral contraceptives, and SJW-warfarin), contraindications (bipolar disorder), therapeutic duplication (antidepressants), and general considerations (phototoxicity and advice to consult a healthcare professional (HCP)). A list of SJW products was identified to assess their labels. Percentages and totals were used to present findings.</p> <p>Results</p> <p>Of the seventy-four products evaluated, no product label provided information for all 8 evaluation criteria. Three products (4.1%) provided information on 7 of the 8 criteria. Four products provided no safety information whatsoever. Percentage of products with label information was: SJW-HIV (8.1%), SJW-immunosupressants (5.4%), SJW-OCPs (8.1%), SJW-warfarin (5.4%), bipolar (1.4%), antidepressants (23.0%), phototoxicity (51.4%), and consult HCP (87.8%). Other safety-related information on labels included warnings about pregnancy (74.3%), lactation (64.9%), discontinue if adverse reaction (23.0%), and not for use in patients under 18 years old (13.5%). The average number of <it>a priori </it>safety issues included on a product label was 1.91 (range 0–8) for 23.9% completeness.</p> <p>Conclusion</p> <p>The vast majority of SJW products fail to adequately address clinically relevant safety issues on their labeling. A few products do provide an acceptable amount of information on clinically relevant safety issues which could enhance the quality of counseling by HCPs and health store clerks. HCPs and consumers may benefit if the FDA re-examined labeling requirements for dietary supplements.</p