Slow conduction and gap junction remodeling in murine ventricle after chronic alcohol ingestion

<p>Abstract</p> <p>Background</p> <p>Long-term heavy alcohol drinkers are prone to the development of cardiac arrhythmia. To understand the mechanisms, we evaluated the cardiac structural and electrophysiological changes in mice chronically drinking excessive alcohol.</p> <p>Results</p> <p>Male C57BL/6J mice were given 36% alcohol in the drinking water. Those given blank water were used as control. Twelve weeks later, the phenotypic characteristics of the heart, including gap junctions and electrical properties were examined. In the alcohol group the ventricles contained a smaller size of cardiomyocytes and a higher density of capillary networks, compared to the control. Western blots showed that, after drinking alcohol, the content of connexin43 (Cx43) protein in the left ventricle was increased by 18% (p < 0.05). Consistently, immunoconfocal microscopy demonstrated that Cx43 gap junctions were up-regulated in the alcohol group with a disorganized distribution, compared to the control. Optical mapping showed that the alcohol group had a reduced conduction velocity (40 ± 18 vs 60 ± 7 cm/sec, p < 0.05) and a higher incidence of ventricular tachyarrhythmia (62% vs 30%, p < 0.05).</p> <p>Conclusion</p> <p>Long-term excessive alcohol intake resulted in extensive cardiac remodeling, including changes in expression and distribution of gap junctions, growth of capillary network, reduction of cardiomyocyte size, and decrease of myocardial conduction.</p

Serine Protease PRSS23 Is Upregulated by Estrogen Receptor α and Associated with Proliferation of Breast Cancer Cells

Serine protease PRSS23 is a newly discovered protein that has been associated with tumor progression in various types of cancers. Interestingly, PRSS23 is coexpressed with estrogen receptor α (ERα), which is a prominent biomarker and therapeutic target for human breast cancer. Estrogen signaling through ERα is also known to affect cell proliferation, apoptosis, and survival, which promotes tumorigenesis by regulating the production of numerous downstream effector proteins

Assessing medical students' performance in core competencies using multiple admission programs for colleges and universities: From the perspective of multi-source feedback

Background: Since 1994, Taiwanese medical universities have employed the multiple application method comprising "recommendations and screening" and "admission application." The purpose of this study is to examine whether medical students admitted using different admission programs gave different performances. Methods: To evaluate the six core competencies for medical students proposed by Accreditation Council for Graduate Medical Education (ACGME), this study employed various assessment tools, including student opinion feedback, multi-source feedback (MSF), course grades, and examination results.MSF contains self-assessment scale, peer assessment scale, nursing staff assessment scale, visiting staff assessment scale, and chief resident assessment scale. In the subscales, the CronbachÊs alpha were higher than 0.90, indicating good reliability. Research participants consisted of 182 students from the School of Medicine at Chang Gung University. Results: Regarding studentsÊ average grade for the medical ethics course, the performance of students who were enrolled through school recommendations exceeded that of students who were enrolled through the National College University Entrance Examination (NCUEE) p = 0.011), and all considered "teamwork" as the most important. Different entry pipelines of students in the "communication," "work attitude," "medical knowledge," and "teamwork" assessment scales showed no significant difference. The improvement rate of the students who were enrolled through the school recommendations was better than that of the students who were enrolled through the N CUEE in the "professional skills," "medical core competencies," "communication," and "teamwork" projects of self-assessment and peer assessment scales. However, the students who were enrolled through the NCUEE were better in the "professional skills," "medical core competencies," "communication," and "teamwork" projects of the visiting staff assessment scale and the chief resident assessment scale. Conclusion: Collectively, the performance of the students enrolled through recommendations was slightly better than that of the students enrolled through the NCUEE, although statistical significance was found in certain parts of the grades only

Candesartan Cilexetil Attenuates Arrhythmogenicity Following Pressure Overload in Rats via the Modulation of Cardiac Electrical and Structural Remodeling and Calcium Handling Dysfunction

Background Cardiac hypertrophy is associated with abnormal electrophysiology and increased arrhythmia risk. This study assessed whether candesartan cilexetil, an angiotensin II type 1 receptor blocker, could suppress arrhythmogenecity by attenuating cardiac electrical remodeling and calcium mishandling in rats with pressure‐overload hypertrophy. Methods and Results Male Sprague‐Dawley rats were randomly subjected to abdominal aorta banding or sham procedure and received either candesartan cilexetil (3.0 mg/kg per day) or vehicle by gavage for 5 weeks. Pressure overload was characterized by compensated left ventricular (LV) hypertrophy and fibrosis, increased LV pressure and its decay time, and prolonged corrected QT interval, all of which were attenuated by candesartan cilexetil treatment. Candesartan cilexetil–treated banded rat hearts displayed shorter QT intervals and lower vulnerability to atrial and ventricular tachyarrhythmias than vehicle‐treated banded hearts. Candesartan cilexetil prevented banding‐induced prolonged action potential duration and reduced the occurrence of triggered activity in LV papillary muscles. In addition, the prolonged time to 50% cell relengthening and calcium transient decay time were normalized in LV myocytes from candesartan cilexetil–treated banded rats, along with a normalization of decreased SERCA2a (sarco[endo]plasmic reticulum calcium‐ATPase) expression in LV tissues. Furthermore, candesartan cilexetil normalized depressed transient outward potassium current densities and protein and mRNA levels of both voltage‐gated potassium 4.2 and 4.3 channel subunits (Kv4.2 and Kv4.3) in banded rats. Conclusions Candesartan cilexetil protects the heart from pressure overload‐induced adverse electrical remodeling by preserving potassium channel densities. In addition, calcium handling and its molecular regulation also improved after treatment. These beneficial effects may contribute to a lower susceptibility to arrhythmias in hearts from candesartan cilexetil–treated pressure‐overloaded rats

In HCV-related liver cirrhosis, local pulse wave velocity increases and in decompensated patients correlates with poorer survival.

BackgroundCirrhotic cardiomyopathy (CCM) refers to cardiac dysfunction in patients with liver cirrhosis, in the absence of other known cardiac disease.MethodsControl group and patients diagnosed of liver cirrhosis without known cardiac disease or hepatocellular carcinoma were enrolled for this clinical observation study. Patients with diabetes mellitus, hypertension were excluded. Absolute global longitudinal strain, one-point carotid pulse wave velocity (one-point PWV) and various parameters were measured in resting status.ResultsThere were 29 participants in the control group and 80 patients in the liver cirrhosis group. 27.8% of cirrhotic patients presented with normal systolic but abnormal diastolic functions and QTc prolongation that were compatible with CCM. 34.2% of cirrhotic patients presented with diastolic dysfunction in resting state comparing to 24.1% in control group. Systolic functions did not show conspicuous difference between cirrhosis and control group nor between compensated and decompensated cirrhosis, neither. Furthermore, one-point PWV was significantly higher in liver cirrhosis than in control group and higher in CCM than in non-CCM patients. One-point PWV predicted CCM and diastolic dysfunction in cirrhosis. Most importantly, its value > 1370cm/s predicted overall mortalities in decompensated cirrhosis (multivariable Cox analysis OR = 6.941) in addition to CTP score specifically in HCV related cirrhotic patients (AUC = 0.817).ConclusionsIn patients with cirrhosis, 27.8% were diagnosed with CCM by resting cardiovascular parameters. One-point PWV increased in CCM, correlated with diastolic dysfunction. It also correlated with overall mortality in patients with hepatitis C virus (HCV) related decompensated cirrhosis. Further study may be needed to confirm its capability for assessing CV and mortality risks in HCV related decompensated cirrhotic patients