Relationship of Enhanced Liver Fibrosis Score with Pediatric Nonalcoholic Fatty Liver Disease Histology and Response to Vitamin E or Metformin

OBJECTIVES: To study the diagnostic performance of the enhanced liver fibrosis score (ELF) for detecting different stages of fibrosis and its usefulness in detecting histologic response to vitamin E or metformin in children with nonalcoholic fatty liver disease who participated in the Vitamin E or Metformin for the Treatment Of NAFLD In Children (TONIC) trial. STUDY DESIGN: ELF was measured at baseline and weeks 24, 48, and 96 on sera from 166 TONIC participants. Associations between ELF with baseline and end of trial (EOT) fibrosis stages and other histologic features were assessed using χ2 tests and logistic regression models. RESULTS: ELF was significantly associated with severity of fibrosis at baseline and EOT. ELF areas under the curve for discriminating patients with clinically significant and advanced fibrosis were 0.70 (95% CI, 0.60-0.80) and 0.79 (95% CI, 0.69-0.89), respectively. A 1-unit decrease in ELF at EOT was associated with overall histologic improvement (OR, 1.86; 95% CI, 1.11-3.14; P = .02), resolution of steatohepatitis (OR, 1.88; 95% CI, 1.09-3.25; P = .02), improvement in steatosis grade (OR, 1.76; 95% CI, 1.06-2.82; P = .03), and hepatocellular ballooning (OR, 1.79; 95% CI, 1.06-3.00; P = .03), but not with improvement in fibrosis stage (OR, 1.26; 95% CI, 0.78-2.03; P = .34). CONCLUSIONS: ELF was associated with fibrosis stage in children who participated in TONIC. Although not associated with improvement in fibrosis, a decrease in ELF at EOT was associated with Nonalcoholic Steatohepatitis resolution and improvement in nonalcoholic fatty liver disease histology. ELF may be a useful noninvasive test to monitor treatment response in children with nonalcoholic fatty liver disease

Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection

Genetic algorithm learning as a robust approach to RNA editing site prediction

BACKGROUND: RNA editing is one of several post-transcriptional modifications that may contribute to organismal complexity in the face of limited gene complement in a genome. One form, known as C → U editing, appears to exist in a wide range of organisms, but most instances of this form of RNA editing have been discovered serendipitously. With the large amount of genomic and transcriptomic data now available, a computational analysis could provide a more rapid means of identifying novel sites of C → U RNA editing. Previous efforts have had some success but also some limitations. We present a computational method for identifying C → U RNA editing sites in genomic sequences that is both robust and generalizable. We evaluate its potential use on the best data set available for these purposes: C → U editing sites in plant mitochondrial genomes. RESULTS: Our method is derived from a machine learning approach known as a genetic algorithm. REGAL (RNA Editing site prediction by Genetic Algorithm Learning) is 87% accurate when tested on three mitochondrial genomes, with an overall sensitivity of 82% and an overall specificity of 91%. REGAL's performance significantly improves on other ab initio approaches to predicting RNA editing sites in this data set. REGAL has a comparable sensitivity and higher specificity than approaches which rely on sequence homology, and it has the advantage that strong sequence conservation is not required for reliable prediction of edit sites. CONCLUSION: Our results suggest that ab initio methods can generate robust classifiers of putative edit sites, and we highlight the value of combinatorial approaches as embodied by genetic algorithms. We present REGAL as one approach with the potential to be generalized to other organisms exhibiting C → U RNA editing

Nursing home administrators’ perspectives on a study feedback report : a cross sectional survey

BackgroundThis project is part of the Translating Research in Elder Care (TREC) program of research, a multi-level and longitudinal research program being conducted in 36 nursing homes in three Canadian Prairie Provinces. The overall goal of TREC is to improve the quality of care for older persons living in nursing homes and the quality of work life for care providers. The purpose of this paper is to report on development and evaluation of facility annual reports (FARs) from facility administrators&rsquo; perspectives on the usefulness, meaningfulness, and understandability of selected data from the TREC survey. MethodsA cross sectional survey design was used in this study. The feedback reports were developed in collaboration with participating facility administrators. FARs presented results in four contextual areas: workplace culture, feedback processes, job satisfaction, and staff burnout. Six weeks after FARs were mailed to each administrator, we conducted structured telephone interviews with administrators to elicit their evaluation of the FARs. Administrators were also asked if they had taken any actions as a result of the FAR. Descriptive and inferential statistics, as well as content analysis for open-ended questions, were used to summarize findings. ResultsThirty-one facility administrators (representing thirty-two facilities) participated in the interviews. Six administrators had taken action and 18 were planning on taking action as a result of FARs. The majority found the four contextual areas addressed in FAR to be useful, meaningful, and understandable. They liked the comparisons made between data from years one and two and between their facility and other TREC study sites in their province. Twenty-two indicated that they would like to receive information on additional areas such as aggressive behaviours of residents and information sharing. Twenty-four administrators indicated that FARs contained enough information, while eight found FARs &lsquo;too short&rsquo;. Administrators who reported that the FAR contained enough information were more likely to take action within their facilities than administrators who reported that they needed more information. ConclusionsAlthough the FAR was brief, the presentation of the four contextual areas was relevant to the majority of administrators and prompted them to plan or to take action within their facility. <br /

Electrophysiologic Studies and Radiofrequency Catheter Ablation of Ectopic Atrial Tachycardia in Children

Ectopic atrial tachycardia (EAT) often resists medical therapy, making radiofrequency catheter ablation (RFCA) the preferred treatment. This study reviewed the records of 35 patients who underwent electrophysiologic studies (EPS) and 39 RFCA procedures for EAT during a 10-year period. Of the 35 patients, 10 (28%) presented with decreased ventricular function and tachycardia-induced cardiomyopathy (TIC). The EAT originated on the right atrial side in 19 patients (54%) and on the left atrial side in the remaining 16 patients (46%). The right atrial sites included the right atrial appendage (RAA) (n = 9, 25%), the tricuspid annulus (n = 7, 20%), and the crista terminalis (n = 3). The left atrial sites included the left atrial appendage (LAA) (n = 6, 17%), the pulmonary veins (n = 5, 14%), the mitral annulus (n = 3), and the posterior wall of the left atrium (n = 2). The mechanism of all EAT probably is automaticity. All EATs could be abolished using RFCA. Follow-up data were available for all patients 2 to 8 years after RFCA. All 35 patients remained recurrence free, and ventricular function improved for all 10 patients with TIC. The origin of EAT in children differed from its origin in adults. The authors conclude that RFCA is a safe and effective treatment option for children with refractory EAT and should be considered early in the course of their illness

Smokers' reactions to FDA regulation of tobacco products: Findings from the 2009 ITC United States survey

<p>Abstract</p> <p>Background</p> <p>On June 22, 2009, the US FDA was granted the authority to regulate tobacco products through the Family Smoking Prevention and Tobacco Control Act (FSPTCA). The intent is to improve public health through regulations on tobacco product marketing and tobacco products themselves. This manuscript reports baseline data on smokers' attitudes and beliefs on specific issues relevant to the FSPTCA.</p> <p>Method</p> <p>Between November 2009 and January 2010, a telephone survey among a nationally representative sample of n = 678 smokers in the US was performed as part of the International Tobacco Control (ITC) United States Survey. Participants answered a battery of questions on their attitudes and beliefs about aspects of the FSPTCA.</p> <p>Results</p> <p>Most smokers were unaware of the new FDA tobacco regulations. Smokers indicated support for banning cigarette promotion and nearly a quarter supported requiring tobacco companies to sell cigarettes in plain packaging. Seventy two percent of smokers supported reducing nicotine levels to make cigarettes less addictive if nicotine was made easily available in non-cigarette form.</p> <p>Conclusion</p> <p>Most smokers were limited in their understanding of efforts to regulate tobacco products in general. Smokers were supportive of efforts to better inform the public about health risks, restrict advertising, and make tobacco products less addictive.</p

Do female association preferences predict the likelihood of reproduction?

Sexual selection acting on male traits through female mate choice is commonly inferred from female association preferences in dichotomous mate choice experiments. However, there are surprisingly few empirical demonstrations that such association preferences predict the likelihood of females reproducing with a particular male. This information is essential to confirm association preferences as good predictors of mate choice. We used green swordtails (&lt;i&gt;Xiphophorus helleri&lt;/i&gt;) to test whether association preferences predict the likelihood of a female reproducing with a male. Females were tested for a preference for long- or short-sworded males in a standard dichotomous choice experiment and then allowed free access to either their preferred or non-preferred male. If females subsequently failed to produce fry, they were provided a second unfamiliar male with similar sword length to the first male. Females were more likely to reproduce with preferred than non-preferred males, but for those that reproduced, neither the status (preferred/non-preferred) nor the sword length (long/short) of the male had an effect on brood size or relative investment in growth by the female. There was no overall preference based on sword length in this study, but male sword length did affect likelihood of reproduction, with females more likely to reproduce with long- than short-sworded males (independent of preference for such males in earlier choice tests). These results suggest that female association preferences are good indicators of female mate choice but that ornament characteristics of the male are also important

A False Start in the Race Against Doping in Sport: Concerns With Cycling’s Biological Passport

Professional cycling has suffered from a number of doping scandals. The sport’s governing bodies have responded by implementing an aggressive new antidoping program known as the biological passport. Cycling’s biological passport marks a departure from traditional antidoping efforts, which have focused on directly detecting prohibited substances in a cyclist’s system. Instead, the biological passport tracks biological variables in a cyclist’s blood and urine over time, monitoring for fluctuations that are thought to indirectly reveal the effects of doping. Although this method of indirect detection is promising, it also raises serious legal and scientific concerns. Since its introduction, the cycling community has debated the reliability of indirect biological-passport evidence and the clarity, consistency, and transparency of its use in proving doping violations. Such uncertainty undermines the legitimacy of finding cyclists guilty of doping based on this indirect evidence alone. Antidoping authorities should address these important concerns before continuing to pursue doping sanctions against cyclists solely on the basis of their biological passports