Examining relationships between resilience protective factors and moral distress among student nurses

Aim: The purpose of this study was to identify relationships between resilience protective factors (RPFs) and moral distress among baccalaureate nursing students. Background: Students report moral distress associated with clinical practicum experiences. Enhancing resilience may minimize moral distress and associated consequences. Method: Correlation, pilot study. Two previously tested instruments were used to measure moral distress (Moral Distress Thermometer) and RPFs (Scale of Protective Factors). Results: Aggregate mean more distress rating was 3.67. Two of four RPF subcategories demonstrated a significant inverse correlation with moral distress rating. Inverse correlations were found between social support and moral distress (r = -.27, p \u3c .05), and between goal efficacy and moral distress (r = -.37, p \u3c .01). Total resilience scores also demonstrated a weak inverse correlation with moral distress (r = -.24, p \u3c .05). Conclusions: Findings help educators prioritize resilience enhancing educational strategies

Global DNA methylation and cognitive and behavioral outcomes at 4 years of age: A cross‐sectional study

Background Accumulating evidence suggests that breastfeeding exclusivity and duration are positively associated with child cognition. This study investigated whether DNA methylation, an epigenetic mechanism modified by nutrient intake, may contribute to the link between breastfeeding and child cognition. The aim was to quantify the relationship between global DNA methylation and cognition and behavior at 4 years of age. Methods Child behavior and cognition were measured at age 4 years using the Wechsler Preschool and Primary Scale of Intelligence, third version (WPPSI‐III), and Child Behavior Checklist (CBC). Global DNA methylation (%5‐methylcytosines (%5mC)) was measured in buccal cells at age 4 years, using an enzyme‐linked immunosorbent assay (ELISA) commercial kit. Linear regression models were used to quantify the statistical relationships. Results Data were collected from 73 children recruited from the Women and Their Children's Health (WATCH) study. No statistically significant associations were found between global DNA methylation levels and child cognition or behavior (p > .05), though the estimates of effect were consistently negative. Global DNA methylation levels in males were significantly higher than in females (median %5mC: 1.82 vs. 1.03, males and females, respectively, (p < .05)). Conclusion No association was found between global DNA methylation and child cognition and behavior; however given the small sample, this study should be pooled with other cohorts in future meta‐analyses

The pestivirus N terminal protease N(pro) redistributes to mitochondria and peroxisomes suggesting new sites for regulation of IRF3 by N(pro.)

The N-terminal protease of pestiviruses, N(pro) is a unique viral protein, both because it is a distinct autoprotease that cleaves itself from the following polyprotein chain, and also because it binds and inactivates IRF3, a central regulator of interferon production. An important question remains the role of N(pro) in the inhibition of apoptosis. In this study, apoptotic signals induced by staurosporine, interferon, double stranded RNA, sodium arsenate and hydrogen peroxide were inhibited by expression of wild type N(pro), but not by mutant protein N(pro) C112R, which we show is less efficient at promoting degradation of IRF3, and led to the conclusion that N(pro) inhibits the stress-induced intrinsic mitochondrial pathway through inhibition of IRF3-dependent Bax activation. Both expression of N(pro) and infection with Bovine Viral Diarrhea Virus (BVDV) prevented Bax redistribution and mitochondrial fragmentation. Given the role played by signaling platforms during IRF3 activation, we have studied the subcellular distribution of N(pro) and we show that, in common with many other viral proteins, N(pro) targets mitochondria to inhibit apoptosis in response to cell stress. N(pro) itself not only relocated to mitochondria but in addition, both N(pro) and IRF3 associated with peroxisomes, with over 85% of N(pro) puncta co-distributing with PMP70, a marker for peroxisomes. In addition, peroxisomes containing N(pro) and IRF3 associated with ubiquitin. IRF3 was degraded, whereas N(pro) accumulated in response to cell stress. These results implicate mitochondria and peroxisomes as new sites for IRF3 regulation by N(pro), and highlight the role of these organelles in the anti-viral pathway

Intracellular interferons in fish : a unique means to combat viral infection

Peer reviewedPublisher PD

Azacytidine and Decitabine Induce Gene-Specific and Non-Random DNA Demethylation in Human Cancer Cell Lines

The DNA methyltransferase inhibitors azacytidine and decitabine represent archetypal drugs for epigenetic cancer therapy. To characterize the demethylating activity of azacytidine and decitabine we treated colon cancer and leukemic cells with both drugs and used array-based DNA methylation analysis of more than 14,000 gene promoters. Additionally, drug-induced demethylation was compared to methylation patterns of isogenic colon cancer cells lacking both DNA methyltransferase 1 (DNMT1) and DNMT3B. We show that drug-induced demethylation patterns are highly specific, non-random and reproducible, indicating targeted remethylation of specific loci after replication. Correspondingly, we found that CG dinucleotides within CG islands became preferentially remethylated, indicating a role for DNA sequence context. We also identified a subset of genes that were never demethylated by drug treatment, either in colon cancer or in leukemic cell lines. These demethylation-resistant genes were enriched for Polycomb Repressive Complex 2 components in embryonic stem cells and for transcription factor binding motifs not present in demethylated genes. Our results provide detailed insights into the DNA methylation patterns induced by azacytidine and decitabine and suggest the involvement of complex regulatory mechanisms in drug-induced DNA demethylation

Computer-aided assessment of diagnostic images for epidemiological research

<p>Abstract</p> <p>Background</p> <p>Diagnostic images are often assessed for clinical outcomes using subjective methods, which are limited by the skill of the reviewer. Computer-aided diagnosis (CAD) algorithms that assist reviewers in their decisions concerning outcomes have been developed to increase sensitivity and specificity in the clinical setting. However, these systems have not been well utilized in research settings to improve the measurement of clinical endpoints. Reductions in bias through their use could have important implications for etiologic research.</p> <p>Methods</p> <p>Using the example of cortical cataract detection, we developed an algorithm for assisting a reviewer in evaluating digital images for the presence and severity of lesions. Available image processing and statistical methods that were easily implementable were used as the basis for the CAD algorithm. The performance of the system was compared to the subjective assessment of five reviewers using 60 simulated images. Cortical cataract severity scores from 0 to 16 were assigned to the images by the reviewers and the CAD system, with each image assessed twice to obtain a measure of variability. Image characteristics that affected reviewer bias were also assessed by systematically varying the appearance of the simulated images.</p> <p>Results</p> <p>The algorithm yielded severity scores with smaller bias on images where cataract severity was mild to moderate (approximately ≤ 6/16^<it>ths</it>). On high severity images, the bias of the CAD system exceeded that of the reviewers. The variability of the CAD system was zero on repeated images but ranged from 0.48 to 1.22 for the reviewers. The direction and magnitude of the bias exhibited by the reviewers was a function of the number of cataract opacities, the shape and the contrast of the lesions in the simulated images.</p> <p>Conclusion</p> <p>CAD systems are feasible to implement with available software and can be valuable when medical images contain exposure or outcome information for etiologic research. Our results indicate that such systems have the potential to decrease bias and discriminate very small changes in disease severity. Simulated images are a tool that can be used to assess performance of a CAD system when a gold standard is not available.</p

Mitochondrial and Plasma Membrane Pools of Stomatin-Like Protein 2 Coalesce at the Immunological Synapse during T Cell Activation

Stomatin-like protein 2 (SLP-2) is a member of the stomatin – prohibitin – flotillin – HflC/K (SPFH) superfamily. Recent evidence indicates that SLP-2 is involved in the organization of cardiolipin-enriched microdomains in mitochondrial membranes and the regulation of mitochondrial biogenesis and function. In T cells, this role translates into enhanced T cell activation. Although the major pool of SLP-2 is associated with mitochondria, we show here that there is an additional pool of SLP-2 associated with the plasma membrane of T cells. Both plasma membrane-associated and mitochondria-associated pools of SLP-2 coalesce at the immunological synapse (IS) upon T cell activation. SLP-2 is not required for formation of IS nor for the re-localization of mitochondria to the IS because SLP-2-deficient T cells showed normal re-localization of these organelles in response to T cell activation. Interestingly, upon T cell activation, we found the surface pool of SLP-2 mostly excluded from the central supramolecular activation complex, and enriched in the peripheral area of the IS where signalling TCR microclusters are located. Based on these results, we propose that SLP-2 facilitates the compartmentalization not only of mitochondrial membranes but also of the plasma membrane into functional microdomains. In this latter location, SLP-2 may facilitate the optimal assembly of TCR signalosome components. Our data also suggest that there may be a net exchange of membrane material between mitochondria and plasma membrane, explaining the presence of some mitochondrial proteins in the plasma membrane

Charting the NF-κB Pathway Interactome Map

Inflammation is part of a complex physiological response to harmful stimuli and pathogenic stress. The five components of the Nuclear Factor κB (NF-κB) family are prominent mediators of inflammation, acting as key transcriptional regulators of hundreds of genes. Several signaling pathways activated by diverse stimuli converge on NF-κB activation, resulting in a regulatory system characterized by high complexity. It is increasingly recognized that the number of components that impinges upon phenotypic outcomes of signal transduction pathways may be higher than those taken into consideration from canonical pathway representations. Scope of the present analysis is to provide a wider, systemic picture of the NF-κB signaling system. Data from different sources such as literature, functional enrichment web resources, protein-protein interaction and pathway databases have been gathered, curated, integrated and analyzed in order to reconstruct a single, comprehensive picture of the proteins that interact with, and participate to the NF-κB activation system. Such a reconstruction shows that the NF-κB interactome is substantially different in quantity and quality of components with respect to canonical representations. The analysis highlights that several neglected but topologically central proteins may play a role in the activation of NF-κB mediated responses. Moreover the interactome structure fits with the characteristics of a bow tie architecture. This interactome is intended as an open network resource available for further development, refinement and analysis

Diagnosis and management of venereal campylobacteriosis in beef cattle

BACKGROUND: Bovine venereal campylobacteriosis is caused by Campylobacter fetus subsp. venerealis and its glycerine-tolerant variant Campylobacter fetus subsp. venerealis biovars intermedius. The disease can be economically important when present in cattle herds, causing poor reproductive performance, embryo mortality and abortion. Sensitive and specific diagnostic tests are required in the diagnosis of infection and to inform and monitor disease control. Current tests include bacterial culture and fluorescent antibody testing of preputial sheath washings and an enzyme-linked immunosorbent assay and an agglutination test on vaginal mucus, although the predictive values of these tests can be inadequate in field investigations. Artificial insemination is often considered as a simple control method for bovine venereal campylobacteriosis, but is impractical for many beef suckler herds where breeding takes place at pasture. Commercial vaccines are unavailable in the UK, while the efficacy of autogenous vaccines using a bacterial isolate from infected animals on a specific farm is at best unproven. Hence, for some infected herds, the development of an alternative control strategy based on segregation of potentially infected and uninfected animals in combination with culling or treatment would be desirable. This approach requires meticulous records and herd health management. CASE PRESENTATION: In this paper we highlight difficulties in diagnosing bovine venereal campylobacteriosis and demonstrate the benefits of good record keeping when investigating poor reproductive performance in a beef suckler herd and establishing a herd-specific approach to bio-containment of the infectious cause. CONCLUSIONS: Bovine venereal campylobacteriosis is an economically important disease that should be considered in investigations of suckler herd subfertility problems. Control of the disease based on segregation of potentially infected and uninfected animals in combination with extensive culling can be achieved without the use of artificial insemination or vaccination, but requires meticulous records and strict adherence to herd biosecurity practices