Citations

Rodent skeletal muscle mitochondrial DNA has been shown to be a potential site of oxidative damage during aging. Caloric restriction (CR) is reported to reduce oxidative stress and prolong life expectancy in rodents. Gene expression profiling and measurement of mitochondrial ATP production capacity were performed in skeletal muscle of male rats after feeding them either a control diet or calorie-restricted diet (60% of control diet) for 36 wk to determine the potential mechanism of the beneficial effects of CR. CR enhanced the transcripts of genes involved in reactive oxygen free radical scavenging function, tissue development, and energy metabolism while decreasing expression of those genes involved in signal transduction, stress response, and structural and contractile proteins. Real-time PCR measurments confirmed the changes in transcript levels of cytochrome- c oxidase III, superoxide dismutase (SOD)1, and SOD2 that were noted by the microarray approach. Mitochondrial ATP production and citrate synthase were unaltered by the dietary changes. We conclude that CR alters transcript levels of several genes in skeletal muscle and that mitochondrial function in skeletal muscle remains unaltered by the dietary intervention. Alterations in transcripts of many genes involved in reactive oxygen scavenging function may contribute to the increase in longevity reported with CR.

High-fat diets are reported to increase oxidative stress in a variety of tissues, whereas antioxidant supplementation prevents many diseases attributed to high-fat diet. Rodent skeletal muscle mitochondrial DNA has been shown to be a potential site of oxidative damage. We hypothesized that the effects of a high-fat diet on skeletal muscle DNA functions would be attenuated or partially reversed by antioxidant supplementation. Gene expression profiling and measurement of mitochondrial ATP production capacity were performed in skeletal muscle from male rats after feeding one of three diets (control, high-fat diet with or without antioxidants) for 36 wk. The high-fat diet altered transcript levels of 18 genes of 800 surveyed compared with the control-fed rats. Alterations included reduced expression of genes involved in free-radical scavenging and tissue development and increased expression of stress response and signal transduction genes. The magnitude of these alterations due to high-fat diet was reduced by antioxidant supplementation. Real-time PCR measurements confirmed the changes in transcript levels of cytochrome c oxidase subunit III and superoxide dismutase-1 and -2 noted by microarray approach. Mitochondrial ATP production was unaltered by dietary changes or antioxidant supplemention. It is concluded that the high-fat diet increases the transcription of genes involved in stress response but reduces those of free-radical scavenger enzymes, resulting in reduced DNA repair/metabolism (increased DNA damage). Antioxidants partially prevent these changes. Mitochondrial functions in skeletal muscle remain unaltered by the dietary intervention due to many adaptive changes in gene transcription.

Objectives: Brush cytology has a low sensitivity for the diagnosis of cholangiocarcinoma. This study aimed to compare the standard approach (brush cytology) with a triple modality approach utilizing brush cytology, forceps biopsy and fluorescence in situ hybridization in terms of sensitivity and specificity for the diagnosis of cholangiocarcinoma. Methods: In a retrospective study at a single academic center, 50 patients underwent triple modality testing. Additionally, 61 patients underwent brush cytology alone. Intervention was endoscopic retrograde cholangiopancreatography with brush cytology, fluorescence in situ hybridization, and forceps biopsy. The main outcome measures included sensitivity, specificity, positive predictive value and negative predictive value. Results: Overall, 50 patients underwent triple tissue sampling, and 61 patients underwent brush cytology alone. Twenty-two patients were eventually diagnosed with cholangiocarcinoma. Brush cytology had a sensitivity of 42%, specificity of 100%, positive predictive value of 100% and negative predictive value of 88%. Triple tissue sampling had an overall sensitivity of 82%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 87%. Within the triple test group, brush cytology had a sensitivity of 27%, forceps biopsy had a sensitivity of 50%, and fluorescence in situ hybridization analysis had a sensitivity of 59%. Conclusions: A triple modality approach results in a marked increase in sensitivity for the diagnosis of cholangiocarcinoma compared with single modality testing such as brush cytology and should be considered in the evaluation of indeterminate or suspicious biliary strictures.

Background— QRS prolongation is associated with adverse outcomes in mostly white populations, but its clinical significance is not well established for other groups. We investigated the association between QRS duration and mortality in African Americans. Methods and Results— We analyzed data from 5146 African Americans in the Jackson Heart Study stratified by QRS duration on baseline 12-lead ECG. We defined QRS prolongation as QRS≥100 ms. We assessed the association between QRS duration and all-cause mortality using Cox proportional hazards models and reported the cumulative incidence of heart failure hospitalization. We identified factors associated with the development of QRS prolongation in patients with normal baseline QRS. At baseline, 30% (n=1528) of participants had QRS prolongation. The cumulative incidences of mortality and heart failure hospitalization were greater with versus without baseline QRS prolongation: 12.6% (95% confidence interval [CI], 11.0–14.4) versus 7.1% (95% CI, 6.3–8.0) and 8.2% (95% CI, 6.9–9.7) versus 4.4% (95% CI, 3.7–5.1), respectively. After risk adjustment, QRS prolongation was associated with increased mortality (hazard ratio, 1.27; 95% CI, 1.03–1.56; P =0.02). There was a linear relationship between QRS duration and mortality (hazard ratio per 10 ms increase, 1.06; 95% CI, 1.01–1.12). Older age, male sex, prior myocardial infarction, lower ejection fraction, left ventricular hypertrophy, and left ventricular dilatation were associated with the development of QRS prolongation. Conclusions— QRS prolongation in African Americans was associated with increased mortality and heart failure hospitalization. Factors associated with developing QRS prolongation included age, male sex, prior myocardial infarction, and left ventricular structural abnormalities.

A point-of-care workflow checklist in the form of an iOS (iPhone Operating System) app for use by stroke providers was introduced with the objective of standardizing acute stroke evaluation and documentation at 2 affiliated academic medical centers. Providers used the app in unselected, consecutive patients undergoing acute stroke evaluation in an emergency department or hospital setting between August 2012 and January 2013 and August 2013 and February 2014. Satisfaction surveys were prospectively collected pre- and postintervention from residents, staff neurologists, and clinical data specialists. Residents (20 preintervention and 16 postintervention), staff neurologists (6 pre and 5 post), and clinical data specialists (4 pre and 4 post) participated in this study. All 16 (100%) residents had increased satisfaction with their ability to perform an acute stroke evaluation postintervention but only 9 (56%) of 16 felt the app was more help than hindrance. Historical controls aligned with preintervention results. Staff neurologists conveyed increased satisfaction with resident presentations and decision making when compared to preintervention surveys. Stroke clinical data specialists estimated a 50% decrease in data abstraction when the app data were used in the clinical note. Concomitant effect on door-to-needle (DTN) time at 1 site, although not a primary study measure, was also evaluated. At that 1 center, the mean DTN time decreased by 16 minutes when compared to the corresponding months from the year prior. The point-of-care acute stroke workflow checklist app may assist trainees in presenting findings in a standardized manner and reduce data abstraction time. The app may help reduce DTN time, but this requires further study.

BackgroundTo evaluate the reliability of MRE using a spin‐echo echo‐planar imaging (SE‐EPI) renal MRE technique in healthy volunteers.MethodsInstitutional review board approved prospective study in which all participants provided written informed consent. Sixteen healthy volunteers comprising seven males and nine females with a median age of 35 years (age range: 23 to 59 years) were included. Coronal 90 Hz and 60 Hz MRE acquisitions were performed twice within a 30‐min interval between examinations. Renal MRE reliability was assessed by (i) test–retest repeatability, and (ii) inter‐rater agreement between two independent readers. The MRE‐measured averaged renal stiffness values were evaluated using: intraclass correlation coefficient (ICC), Bland‐Altman and the within‐subject coefficient of variation (COV).ResultsFor test–retest repeatability, Bland‐Altman showed a mean stiffness difference between examinations of 0.07 kPa (95% limits of agreement: −1.41, 1.54) at 90 Hz and 0.01 kPa (95% limits of agreement: −0.51, 0.53) at 60 Hz. Coefficient of repeatability was 1.47 kPa and 0.52 kPa at 90 Hz and 60 Hz, respectively. The within‐subject COV was 13.6% and 7.7% at 90 Hz and 60 Hz, respectively. ICC values were 0.922 and 0.907 for test–retest repeatability and 0.998 and 0.989 for inter‐rater agreement, respectively (P < 0.001).ConclusionSE‐EPI renal MRE is a reliable technique. J. Magn. Reson. Imaging 2015;42:844–850.