Molecular danger signals attract neutrophilic granulocytes (polymorphonuclear leukocytes (PMNs)) to sites of infection. The G protein-coupled receptor (GPR) 43 recognizes propionate and butyrate and is abundantly expressed on PMNs. The functional role of GPR43 activation for in vivo orchestration of immune response is unclear. We examined dextrane sodium sulfate (DSS)-induced acute and chronic intestinal inflammatory response in wild-type and Gpr43-deficient mice. The severity of colonic inflammation was assessed by clinical signs, histological scoring, and cytokine production. Chemotaxis of wild-type and Gpr43-deficient PMNs was assessed through transwell cell chemotactic assay. A reduced invasion of PMNs and increased mortality due to septic complications were observed in acute DSS colitis. In chronic DSS colitis, Gpr43−/− animals showed diminished PMN intestinal migration, but protection against inflammatory tissue destruction. No significant difference in PMN migration and cytokine secretion was detected in a sterile inflammatory model. Ex vivo experiments show that GPR43-induced migration is dependent on activation of the protein kinase p38α, and that this signal acts in cooperation with the chemotactic cytokine keratinocyte chemoattractant. Interestingly, shedding of L-selectin in response to propionate and butyrate was compromised in Gpr43−/− mice. These results indicate a critical role for GPR43-mediated recruitment of PMNs in containing intestinal bacterial translocation, yet also emphasize the bipotential role of PMNs in mediating tissue destruction in chronic intestinal inflammation.

Aims.To evaluate the prognostic value of the QT interval and QT interval dispersion in total and in cardiovascular mortality, as well as in cardiac morbidity, in a general population.Methods and results. The QT interval was measured in all leads from a standard 12-lead ECG in a random sample of 1658 women and 1797 men aged 30-60 years. QT interval dispersion was calculated from the maximal difference between QT intervals in any two leads. All cause mortality over 13 years, and cardiovascular mortality as well as cardiac morbidity over 11 years, were the main outcome parameters. Subjects with a prolonged QT interval (430 ms or more) or prolonged QT interval dispersion (80 ms or more) were at higher risk of cardiovascular death and cardiac morbidity than subjects whose QT interval was less than 360 ms, or whose QT interval dispersion was less than 30 ms. Cardiovascular death relative risk ratios, adjusted for age, gender, myocardial infarct, angina pectoris, diabetes mellitus, arterial hypertension, smoking habits, serum cholesterol level, and heart rate were 2·9 for the QT interval (95% confidence interval 1·1-7·8) and 4·4 for QT interval dispersion (95% confidence interval 1·0-19·1). Fatal and non-fatal cardiac morbidity relative risk ratios were similar, at 2·7 (95% confidence interval 1·4-5·5) for the QT interval and 2·2 (95% confidence interval 1·1-4·0) for QT interval dispersion. Conclusion.Prolongation of the QT interval and QT interval dispersion independently affected the prognosis of cardiovascular mortality and cardiac fatal and non-fatal morbidity in a general population over 11 years.

A long-standing challenge in optical neuroimaging has been the assessment of hemodynamics and oxygen metabolism in the awake rodent brain at the microscopic level. Here, we report first-of-a-kind head-restrained photoacoustic microscopy (PAM), which enables simultaneous imaging of the cerebrovascular anatomy, total concentration and oxygen saturation of hemoglobin, and blood flow in awake mice. Combining these hemodynamic measurements allows us to derive two key metabolic parameters—oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2). This enabling technology offers the first opportunity to comprehensively and quantitatively characterize the hemodynamic and oxygen-metabolic responses of the mouse brain to isoflurane, a general anesthetic widely used in preclinical research and clinical practice. Side-by-side comparison of the awake and anesthetized brains reveals that isoflurane induces diameter-dependent arterial dilation, elevated blood flow, and reduced OEF in a dose-dependent manner. As a result of the combined effects, CMRO2 is significantly reduced in the anesthetized brain under both normoxia and hypoxia, which suggests a mechanism for anesthetic neuroprotection. The head-restrained functional and metabolic PAM opens a new avenue for basic and translational research on neurovascular coupling without the strong influence of anesthesia and on the neuroprotective effects of various interventions, including but not limited to volatile anesthetics, against cerebral hypoxia and ischemia.

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Purpose More than 50,000 Americans were diagnosed with kidney and renal pelvis cancer in 2010. The National Program of Cancer Registries and SEER (Surveillance, Epidemiology and End Results) combined data include cancer incidences from the entire United States. Our study presents updated incidence data, evaluates trends and adds geographic distribution to the literature. Materials and Methods We examined invasive, microscopically confirmed kidney and renal pelvis cancers diagnosed from 2001 to 2010 that met United States Cancer Statistics reporting criteria for each year, excluding cases diagnosed by autopsy or death certificate. Histology codes classified cases as renal cell carcinoma. Rates and trends were estimated using SEER*Stat. Results A total of 342,501 renal cell carcinoma cases were diagnosed. The renal cell carcinoma incidence rate increased from 10.6/100,000 individuals in 2001 to 12.4/100,000 in 2010 and increased with age until ages 70 to 74 years. The incidence rate in men was almost double that in women. The annual percent change was higher in women than in men, in those 20 to 24 years old and in grade III tumors. Conclusions The annual percent change incidence increased from 2001 to 2010. Asian/Pacific Islanders and 20 to 24-year-old individuals had the highest annual percent change. While some increase resulted from localized disease, the highest annual percent change was in grade III tumors, indicating more aggressive disease. Continued monitoring of trends and epidemiological study are warranted to determine risk factors.

Transcatheter device closure and surgical repair are effective interventions with excellent midterm results for treating pmVSD in children. Transcatheter device closure has a lower incidence of myocardial injury, less blood transfused, faster recovery, shorter hospital stay, and lower medical expenses. (Transcatheter Closure Versus Surgery of Perimembranous Ventricular Septal Defects; NCT00890799).

Incorporating walnuts into the diet improved blood lipid profile without adversely affecting body weight or blood pressure.

Postoperative cognitive dysfunction is a commonly recognized complication after cardiac surgery. Intraoperative cerebral microembolism and hypoperfusion have been proposed to be the major mechanisms. The results of this study show that intraoperative administration of lidocaine decreased the occurrence of early postoperative cognitive dysfunction, perhaps because of its neuroprotective effects.