Role of PPARα and Its Agonist in Renal Diseases

Peroxisome proliferator-activated receptor (PPAR)-α, a member of a large nuclear receptor superfamily, plays a major role in the regulation of lipid metabolism. Recently, PPARα activation has been shown to confer additional benefits on endothelial function, kidney function, and anti-inflammation, suggesting that PPARα agonists may be good candidates for treating acute renal failure. In clinical application, PPAR-α activators, such as hypolipidemic drugs in fibric acid class, were proven to have therapeutic effects on metabolic syndrome and cardiovascular disease. This paper focuses on signaling pathways, ligand selectivity, and physio-pathological roles of PPARα in kidney diseases and the therapeutic utility of PPARα modulators in the treatment of diabetes and inflammation-induced nephropathy. Implication of new and more potent PPAR-α activators could provide important insights into the overall benefits of activating PPAR-α clinically for the treatment of dyslipidemia and the prevention of diabetic or inflammation-induced nephropathy in the future

Dermatofibrosarcoma protuberans: A 10-year experience

SummaryBackgroundProviding soft-tissue coverage after wide excision of dermatofibrosarcoma protuberans (DFSP) is always challenging; according to the literature, a skin graft is often chosen as the first option. However, possible suboptimal functional and cosmetic results have been noted.Aims and objectivesWe present our 10-year experience using pedicled or free flaps for reconstruction after a wide excision of DFSP to provide adequate soft-tissue augmentation and enhanced esthetic results.Materials and methodsThis was a retrospective study comprising 14 DFSP patients who were treated between February 2003 and December 2013. All patients underwent a wide excision with a 3-cm safe margin with immediate reconstruction, and a negative deep margin confirmed with a frozen section. The reconstruction method included nine pedicled perforator flaps and five free perforator flaps. All patients received adjuvant radiotherapy after surgery.ResultsThe peak incidence that occurred in this series was the highest in patients younger than 30 years. None of the 14 patients exhibited recurrence, and the mean follow-up time was 30 months. Half of the patients exhibited DFSP distributed over the trunk; the patients in the series were predominantly male. A total of 13 flaps were successful except for one pedicled flap that failed from venous congestion; we used it in a salvage procedure by using full-thickness skin graft for coverage.ConclusionA wide excision with a 3-cm margin of safety with immediate reconstruction is a reliable method for DFSP resection. Initiating adjuvant radiotherapy might reduce the chance of local recurrence. To minimize the complications of skin graft, pedicled, or free flaps provide superior functional outcome, soft-tissue augmentation, and esthetic results

Size, Temperature, and Strain-Rate Dependence on Tensile Mechanical Behaviors of Ni 3

This study focuses on exploring the mechanical properties and nonlinear stress-strain behaviors of monoclinic Ni3Sn4 single crystals under uniaxial tensile test and also their size, temperature, and strain-rate dependence through constant temperature molecular dynamics (MD) simulation using Berendsen thermostat. The deformation evolution of the Ni3Sn4 atomic nanostructure during the tensile test is observed. In addition, the tensile yield strains of various Ni3Sn4 single crystals at different strain rates and temperatures are characterized through unloading process. At last, by way of linear regression analysis, the corresponding normal elastic stiffness constants are approximated and then compared with the literature theoretical data. The radial distribution function analysis shows that Ni3Sn4 single crystal in a one-dimensional nanowire configuration would become a highly disordered structure after thermal equilibration, thereby possessing amorphous-like mechanical behaviors and properties. The initial elastic deformation of Ni3Sn4 single crystal is governed by the reconfiguration of surface atoms, and its deformation evolution after further uniaxial tensile straining is characterized by Ni=Sn bond straightening, bond breakage, inner atomic distortion, cross-section shrinking, and rupture. The calculated normal elastic constants of Ni3Sn4 single crystal are found to be consistent with the literature theoretical data

EFFECTS OF WHOLE BODY VIBRATION TRAINING ON KNEE EXTENSOR MUSCLE STRENGTH AND RATE OF FORCE DEVELOPMENT

This study compared the effects of 8-week whole-body vibration (WBV) training programs on knee extensor muscle strength and rate of force development. Twenty physically active male subjects were randomly assigned to a whole-body vibration training group (WBV; n =10) or a sham training group (SHAM; n = 10). Maximal voluntary isometric joint moment, rate of force development (RFD) and contractile impulse of the knee extensors were assessed before and after the training period. There were significant differences between WBV and sham groups on improvement percentage of maximum joint moment, RFD and contractile impulse in knee extensor. We concluded that not only knee extensor muscle strength could be enhanced but also muscle contractile abilty could be faster after a 8-week WBV training program

Temporal and Spatial Properties of Arterial Pulsation Measurement Using Pressure Sensor Array

Conventionally, a pulse taking platform is based on a single sensor, which initiates a feasible method of quantitative pulse diagnosis. The aim of this paper is to implement a pulse taking platform with a tactile array sensor. Three-dimensional wrist pulse signals are constructed, and the length, width, ascending slope, and descending slope are defined following the surface of the wrist pulse. And the pressure waveform of the wrist pulse obtained through proposed pulse-taking platform has the same performance as the single sensor. Finally, the results of a paired samples t-test reveal that the repeatability of the proposal platform is consistent with clinical experience. On the other hand, the results of ANOVA indicate that differences exist among different pulse taking depths, and this result is consistent with clinical experience in traditional Chinese medicine pulse diagnosis (TCMPD). Hence, the proposed pulse taking platform with an array sensor is feasible for quantification in TCMPD

Association between health examination items and body mass index among school children in Hualien, Taiwan

BACKGROUND: To assess the prevalence of obesity and major physical examination items including dental caries, myopia, pinworm, hematuria, and proteinuria among school children in Hualien, Taiwan. In addition, the health status differences between gender, grader, levels of residence urbanization, and body mass index (BMI) were examined. METHODS: Cross-sectional studies with a total of 11,080 students (age, 7–14 years) in grades 1, 4, and 7 were evaluated for weight, height, routine physical examination, and urine analysis during the 2010 Student Health Examination in Hualien. Frequencies, Chi-square test, and logistic regression were conducted using SPSS. RESULTS: Of the 11,080 students evaluated, 1357 (12.2%) were overweight, and 1421 (12.8%) were obese. There were significant differences in overweight/obese prevalence by gender, by grader, and by levels of residence urbanization. Dental caries, myopia, and obesity were the most prevalent health problems among these students (75.6%, 33.0%, and 12.8%, respectively). In crude and adjusted analyses, research results showed that there were significant differences in the prevalence of major physical examination items between different gender, grader, levels of residence urbanization, and BMI groups. Girls had a higher prevalence of dental caries, myopia, and hematuria than boys (all p < 0.01), whereas boys had a higher prevalence of pinworm than girls (p = 0.02). Students in higher grades had significantly higher prevalence of myopia, hematuria, and proteinuria (all p < 0.01), whereas students in lower grades had higher prevalence of dental caries and pinworm (p < 0.01). Students with abnormal BMI had lower prevalence of pinworm (p < 0.01). Students residing in suburban and rural areas had higher prevalence of dental caries, pinworm, and hematuria (all p < 0.01), and lower prevalence of myopia than students residing in urban areas (all p < 0.01). CONCLUSION: Routine health examination provides an important way to detect students’ health problems. Our study elucidated major health problems among school children in Hualien, Taiwan. In addition, the results also indicated that the prevalence of health problems had a significant relationship with gender, grader, levels of residence urbanization, and BMI. It is suggested that school health interventions should consider students’ health profiles along with their risk factors status in planning

Metabolic Stress-Induced Phosphorylation of KAP1 Ser473 Blocks Mitochondrial Fusion in Breast Cancer Cells

Mitochondrial dynamics during nutrient starvation of cancer cells likely exert profound effects on their capability for metastatic progression. Here, we report that KAP1 (TRIM28), a transcriptional coadaptor protein implicated in metastatic progression in breast cancer, is a pivotal regulator of mitochondrial fusion in glucose-starved cancer cells. Diverse metabolic stresses induced Ser473 phosphorylation of KAP1 (pS473-KAP1) in a ROS- and p38-dependent manner. Results from live-cell imaging and molecular studies revealed that during the first 6 to 8 hours of glucose starvation, mitochondria initially underwent extensive fusion, but then subsequently fragmented in a pS473-KAP1-dependent manner. Mechanistic investigations using phosphorylation-defective mutants revealed that KAP1 Ser473 phosphorylation limited mitochondrial hyperfusion in glucose-starved breast cancer cells, as driven by downregulation of the mitofusin protein MFN2, leading to reduced oxidative phosphorylation and ROS production. In clinical specimens of breast cancer, reduced expression of MFN2 corresponded to poor prognosis in patients. In a mouse xenograft model of human breast cancer, there was an association in the core region of tumors between MFN2 downregulation and the presence of highly fragmented mitochondria. Collectively, our results suggest that KAP1 Ser473 phosphorylation acts through MFN2 reduction to restrict mitochondrial hyperfusion, thereby contributing to cancer cell survival under conditions of sustained metabolic stress

Effectiveness of mechanical chest compression for out-of-hospital cardiac arrest patients in an emergency department

AbstractBackgroundTo increase the chance of restoring spontaneous circulation, cardiopulmonary resuscitation (CPR) with high-quality chest compressions is needed. We hypothesized that, in a municipal hospital emergency department, the outcome in nontraumatic out-of-hospital cardiac arrest patients treated with standard CPR followed by mechanical chest compression (MeCC) was not inferior to that followed by manual chest compression (MaCC). The purposes of the study were to test our hypothesis and investigate whether the use of MeCC decreased human power demands for CPR.MethodsA total of 455 consecutive out-of-hospital cardiac arrest patients of presumed cardiac etiology were divided into two groups according to the chest compressions they received (MaCC or MeCC) in this retrospective review study. Human power demand for CPR was described according to the Basic Life Support/Advanced Cardiovascular Life Support guidelines and the device handbook. The primary endpoint was recovery of spontaneous circulation during resuscitation, and the secondary endpoints were survival to hospital admission and medical human power demands.ResultsIn this study, recovery of spontaneous circulation was achieved in 33.3% of patients in the MeCC group and in 27.1% in the MaCC group (p = 0.154), and the percentages of patients who survived hospitalization were 22.2% and 17.6%, respectively (p = 0.229). A ratio of 2:4 for the human power demand for CPR between the groups was found. Independent predictors of survival to hospitalization were ventricular fibrillation/pulseless ventricular tachycardia as initial rhythm and recovery of spontaneous circulation.ConclusionNo difference was found in early survival between standard CPR performed with MeCC and that performed with MaCC. However, the use of the MeCC device appears to promote staff availability without waiving patient care in the human power-demanding emergency departments of Taiwan hospitals

Pathological Ace2-to-Ace enzyme switch in the stressed heart is transcriptionally controlled by the endothelial Brg1–FoxM1 complex

Genes encoding angiotensin-converting enzymes (Ace and Ace2) are essential for heart function regulation. Cardiac stress enhances Ace, but suppresses Ace2, expression in the heart, leading to a net production of angiotensin II that promotes cardiac hypertrophy and fibrosis. The regulatory mechanism that underlies the Ace2-to-Ace pathological switch, however, is unknown. Here we report that the Brahma-related gene-1 (Brg1) chromatin remodeler and forkhead box M1 (FoxM1) transcription factor cooperate within cardiac (coronary) endothelial cells of pathologically stressed hearts to trigger the Ace2-to-Ace enzyme switch, angiotensin I-to-II conversion, and cardiac hypertrophy. In mice, cardiac stress activates the expression of Brg1 and FoxM1 in endothelial cells. Once activated, Brg1 and FoxM1 form a protein complex on Ace and Ace2 promoters to concurrently activate Ace and repress Ace2, tipping the balance to Ace2 expression with enhanced angiotensin II production, leading to cardiac hypertrophy and fibrosis. Disruption of endothelial Brg1 or FoxM1 or chemical inhibition of FoxM1 abolishes the stress-induced Ace2-to-Ace switch and protects the heart from pathological hypertrophy. In human hypertrophic hearts, BRG1 and FOXM1 expression is also activated in endothelial cells; their expression levels correlate strongly with the ACE/ACE2 ratio, suggesting a conserved mechanism. Our studies demonstrate a molecular interaction of Brg1 and FoxM1 and an endothelial mechanism of modulating Ace/Ace2 ratio for heart failure therapy