CydDC-mediated reductant export in Escherichia coli controls the transcriptional wiring of energy metabolism and combats nitrosative stress

The glutathione/cysteine exporter CydDC maintains redox balance in Escherichia coli. A cydD mutant strain was used to probe the influence of CydDC upon reduced thiol export, gene expression, metabolic perturbations, intracellular pH homeostasis, and tolerance to nitric oxide (NO). Loss of CydDC was found to decrease extracytoplasmic thiol levels, whereas overexpression diminished the cytoplasmic thiol content. Transcriptomic analysis revealed a dramatic up-regulation of protein chaperones, protein degradation (via phenylpropionate/phenylacetate catabolism), ?-oxidation of fatty acids, and genes involved in nitrate/nitrite reduction. 1H NMR metabolomics revealed elevated methionine and betaine and diminished acetate and NAD+ in cydD cells, which was consistent with the transcriptomics-based metabolic model. The growth rate and ?pH, however, were unaffected, although the cydD strain did exhibit sensitivity to the NO-releasing compound NOC-12. These observations are consistent with the hypothesis that the loss of CydDC-mediated reductant export promotes protein misfolding, adaptations to energy metabolism, and sensitivity to NO. The addition of both glutathione and cysteine to the medium was found to complement the loss of bd -type cytochrome synthesis in a cydD strain (a key component of the pleiotropic cydDC phenotype), providing the first direct evidence that CydDC substrates are able to restore the correct assembly of this respiratory oxidase. These data provide an insight into the metabolic flexibility of E. coli , highlight the importance of bacterial redox homeostasis during nitrosative stress, and report for the first time the ability of periplasmic low molecular weight thiols to restore haem incorporation into a cytochrome complex

Solving Einstein's equations for rotating spacetimes: Evolution of relativistic star clusters

A numerical relativity code designed to evolve rotating axisymmetric spacetimes is constructed. Both polarization states of gravitational radiation can be tracked. The source of the gravitational field is chosen to be a configuration of collisionless particles. The code is used to evaluate the stability of polytropic and toroidal star clusters. The formation of Kerr black holes by the collapse of unstable clusters is demonstrated. Unstable clusters with J/(M^2) 1 collapse to new equilibrium configurations

Sepsis biomarkers in unselected patients on admission to intensive or high-dependency care

Although many sepsis biomarkers have shown promise in selected patient groups, only C-reactive protein and procalcitonin (PCT) have entered clinical practice. The aim of this study was to evaluate three promising novel sepsis biomarkers in unselected patients at admission to intensive care. We assessed the performance of pancreatic stone protein (PSP), soluble CD25 (sCD25) and heparin binding protein (HBP) in distinguishing patients with sepsis from those with a non-infective systemic inflammatory response and the ability of these markers to indicate severity of illness. METHODS: Plasma levels of the biomarkers, PCT and selected inflammatory cytokines were measured in samples taken from 219 patients during the first six hours of admission to intensive or high dependency care. Patients with a systemic inflammatory response were categorized as having sepsis or a non-infective aetiology, with or without markers of severity, using standard diagnostic criteria. RESULTS: Both PSP and sCD25 performed well as biomarkers of sepsis irrespective of severity of illness. For both markers the area under the receiver operating curve (AUC) was greater than 0.9; PSP 0.927 (0.887 to 0.968) and sCD25 0.902 (0.854 to 0.949). Procalcitonin and IL6 also performed well as markers of sepsis whilst in this intensive care unit (ICU) population, HBP did not: PCT 0.840 (0.778 to 0.901), IL6 0.805 (0.739 to 0.870) and HBP 0.607 (0.519 to 0.694). Levels of both PSP and PCT reflected severity of illness and both markers performed well in differentiating patients with severe sepsis from severely ill patients with a non-infective systemic inflammatory response: AUCs 0.955 (0.909 to 1) and 0.837 (0.732 to 0.941) respectively. Although levels of sCD25 did not correlate with severity, the addition of sCD25 to either PCT or PSP in a multivariate model improved the diagnostic accuracy of either marker alone. CONCLUSIONS: PSP and sCD25 perform well as sepsis biomarkers in patients with suspected sepsis at the time of admission to intensive or high dependency care. These markers warrant further assessment of their prognostic value. Whereas previously published data indicate HBP has clinical utility in the emergency department, it did not perform well in an intensive-care population

Substance Use as a Longitudinal Predictor of the Perpetration of Teen Dating Violence

The final publication is available at Springer via http://dx.doi.org/10.1007/s10964-012-9877-1.The prevention of teen dating violence is a major public health priority. However, the dearth of longitudinal studies makes it difficult to develop programs that effectively target salient risk factors. Using a school-based sample of ethnically diverse adolescents, this longitudinal study examined whether substance use (alcohol, marijuana, and hard drugs) and exposure to parental violence predicted the perpetration of physical dating violence over time. 1,042 9th and 10th grade high schools students were recruited and assessed in the spring of 2010, and 93% of the original sample completed the 1-year follow-up in the spring of 2011. Participants who had begun dating at the initial assessment and who self-identified as African American (n = 263; 32%), Caucasian (n = 272; 33%), or Hispanic (n = 293; 35%) were included in the current analyses (n = 828; 55% female). Slightly more than half of the adolescents who perpetrated dating violence at baseline reported past year dating violence at follow-up, relative to only 11% of adolescents who did not report perpetrating dating violence at baseline. Structural equation modeling revealed that the use of alcohol and hard drugs at baseline predicted the future perpetration of physical dating violence, even after accounting for the effects of baseline dating violence and exposure to interparental violence. Despite differences in the prevalence of key variables between males and females, the longitudinal associations did not vary by gender. With respect to race, exposure to mother-to-father violence predicted the perpetration of dating violence among Caucasian adolescents. Findings from the current study indicate that targeting substance use, and potentially youth from violent households, may be viable approaches to preventing the perpetration of teen dating violence

The role of discharge variability in determining alluvial stratigraphy

We illustrate the potential for using physics-based modeling to link alluvial stratigraphy to large river morphology and dynamics. Model simulations, validated using ground penetrating radar data from the Río Paraná, Argentina, demonstrate a strong relationship between bar-scale set thickness and channel depth, which applies across a wide range of river patterns and bar types. We show that hydrologic regime, indexed by discharge variability and flood duration, exerts a first-order influence on morphodynamics and hence bar set thickness, and that planform morphology alone may be a misleading variable for interpreting deposits. Indeed, our results illustrate that rivers evolving under contrasting hydrologic regimes may have very similar morphology, yet be characterized by marked differences in stratigraphy. This realization represents an important limitation on the application of established theory that links river topography to alluvial deposits, and highlights the need to obtain field evidence of discharge variability when developing paleoenvironmental reconstructions. Model simulations demonstrate the potential for deriving such evidence using metrics of paleocurrent variance

Evaluating Adults With Idiopathic Pancreatitis for Genetic Predisposition: Higher Prevalence of Abnormal Results With Use of Complete Gene Sequencing

OBJECTIVES: In adults with unexplained pancreatitis, the yield of complete gene versus select exosome sequencing on mutation detection and distinguishing clinical characteristics associated with mutations requires clarification. We sought to (1) compare frequency of mutations identified using different techniques and (2) compare clinical characteristics between adults with and without mutations. METHODS: This is a cohort study of adults with unexplained pancreatitis who underwent genetic testing between January 2008 and December 2012. We compare probabilities of having a positive mutation with complete gene sequencing versus alternatives and describe differences in characteristics among patients with and without mutations. RESULTS: Of the 370 patients, 67 (18%) had a genetic mutation; 24 (6%) were of high risk. Mutations were significantly more prevalent with use of complete sequencing (42%) versus other approaches (8%, P < 0.0001). Most (44/67, 66%) with a mutation had no family history. Those with high-risk mutations were more likely to have a family history of chronic pancreatitis (21% vs 4%, P = 0.002). Patients with pancreas divisum were more likely to have mutations (27% vs 14%, P = 0.0007). CONCLUSION: Among individuals with adult-onset pancreatic disease, the probability of finding any mutation, including high risk, is significantly higher using complete gene sequencing. The impact on patients and providers requires further investigation

Sleep regularity and predictors of sleep efficiency and sleep duration in elite team sport athletes

Background Many elite athletes have suboptimal sleep duration and efficiency, potentially due to factors that may impact sleep onset and offset times. Variability in sleep onset and offset may negatively influence sleep. The sleep regularity index (SRI) is a novel metric for sleep regularity, however there are no published descriptions of SRI in elite athletes. Further, contributors to sleep efficiency and duration in elite athletes using objective measures have not been explored. Methods Sleep was monitored over a minimum of seven consecutive days (7 to 43)—in 203 elite team sport athletes (age range = 19–36 years; female, n = 79; male, n = 124, total sleep nights = 1975) using activity monitoring and sleep diaries. The sleep regularity index (SRI) was calculated to reflect the night-to-night shifts in sleep by accounting for changes in sleep onset and sleep offset. Sleep characteristics were compared between regular and irregular sleepers and important contributors to sleep efficiency and total sleep time were assessed using multiple linear regression models. Results The median sleep regularity index and interquartile range were 85.1 (81.4 to 88.8). When compared to irregular sleepers, regular sleepers demonstrated (1) significantly greater sleep efficiency (p = 0.006; 0.31 medium effect size [ES]), (2) significantly less variability in total sleep time (− p ≤ 0.001; − 0.69, large ES) and sleep efficiency (− 0.34, small ES), (3) similar total sleep time and (4) significantly less variation in sleep onset (p ≤ 0.001; − 0.73, large ES) and offset (p ≤ 0.001; − 0.74, large ES) times. Sleep characteristics explained 73% and 22% of the variance in total sleep time and sleep efficiency, respectively. The most important contributor to total sleep time was a later sleep offset time, while the most important contributors to sleep efficiency were an earlier bedtime and less variable sleep onset times. Conclusions Bedtime and a consistent sleep onset time are important factors associated with sleep efficiency in athletes, while sleep offset is an important factor for total sleep time. Coaches and staff can assist their athletes by providing training schedules that allow for both regularity and sufficiency of time in bed where possible

Endoscopic papillectomy: risk factors for incomplete resection and recurrence during long-term follow-up

Background Endoscopic papillectomy is increasingly used as an alternative to surgery for ampullary adenomas and other noninvasive ampullary lesions. Objective To measure short-term safety and efficacy of endoscopic papillectomy, define patient and lesion characteristics associated with incomplete endoscopic resection, and measure adenoma recurrence rates during long-term follow-up. Design Retrospective cohort study. Setting Tertiary-care academic medical center. Patients All patients who underwent endoscopic papillectomy for ampullary lesions between July 1995 and June 2012. Intervention Endoscopic papillectomy. Main Outcome Measurements Patient and lesion characteristics associated with incomplete endoscopic resection and ampullary adenoma-free survival analysis. Results We identified 182 patients who underwent endoscopic papillectomy, 134 (73.6%) having complete resection. Short-term adverse events occurred in 34 (18.7%). Risk factors for incomplete resection were jaundice at presentation (odds ratio [OR] 0.21, 95% confidence interval [CI] 0.07–0.69; P = .009), occult adenocarcinoma (OR 0.06, 95% CI, 0.01–0.36; P = .002), and intraductal involvement (OR 0.29, 95% CI, 0.11–0.75; P = .011). The en bloc resection technique was strongly associated with a higher rate of complete resection (OR 4.05, 95% CI, 1.71–9.59; P = .001). Among patients with ampullary adenoma who had complete resection (n = 107), 16 patients (15%) developed recurrence up to 65 months after resection. Limitations Retrospective analysis. Conclusion Jaundice at presentation, occult adenocarcinoma in the resected specimen, and intraductal involvement are associated with a lower rate of complete resection, whereas en bloc papillectomy increases the odds of complete endoscopic resection. Despite complete resection, recurrence was observed up to 5 years after papillectomy, confirming the need for long-term surveillance

Psychological Abuse, Mental Health, and Acceptance of Dating Violence Among Adolescents

Purpose Existing literature indicates that acceptance of dating violence is a significant and robust risk factor for psychological dating abuse perpetration. Past work also indicates a significant relationship between psychological dating abuse perpetration and poor mental health. However, no known research has examined the relationship between acceptance of dating violence, perpetration of dating abuse, and mental health. In addition to exploring this complex relationship, the present study examines whether psychological abuse perpetration mediates the relationship between acceptance of dating violence and mental health (i.e., internalizing symptoms of depression, anxiety, and hostility). Methods Three waves of longitudinal data were obtained from 1,042 ethnically diverse high school students in Texas. Participants completed assessments of psychological dating abuse perpetration, acceptance of dating violence, and internalizing symptoms (hostility and symptoms of anxiety and depression). Results As predicted, results indicated that perpetration of psychological abuse was significantly associated with acceptance of dating violence and all internalizing symptoms. Furthermore, psychological abuse mediated the relationship between acceptance of dating violence and internalizing symptoms. Conclusions Findings from the present study suggest that acceptance of dating violence is an important target for the prevention of dating violence and related emotional distress