Enhancement of beta-catenin in cardiomyocytes suppresses survival protein expression but promotes apoptosis and fibrosis

Background: Beta-catenin has been implicated in cell-cell communication in a wide variety of developmental and physiological processes. Defective Wnt signaling could result in various cardiac and vascular abnormalities. Little is known regarding Wnt/frizzled pathway in cardiomyocyte apoptosis. Methods: In this study, the role of b-catenin in apoptosis was investigated in H9c2 cardiomyocytes and primary cardiomyocytes isolated in diabetic Wistar rats. The cardiomyocytes were transfected with porcine cytomegalovirus (pCMV)-b-catenin plasmid in order to overexpress b-catenin. Results: The transcription factor displayed a significant nuclear localization in Wistar rats with cardiac hypertension. Transfection of b-catenin plasmid induced apoptosis and reduced expression of survival pathway markers in cardiomyocytes in a dose-dependent manner. Furthermore, expression of fibrosis protein markers was upregulated by the overexpression. Conclusions: Taken together, these results revealed that altered Wnt/b-catenin signaling might provoke heart failure. (Cardiol J 2017; 24, 2: 195–205

DC-SIGN (CD209) Promoter −336 A/G Polymorphism Is Associated with Dengue Hemorrhagic Fever and Correlated to DC-SIGN Expression and Immune Augmentation

Dengue fever (DF) is an arthropod-borne disease that is prevalent in tropical and subtropical regions of the world. DC-SIGN [dendritic cell-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing non-integrin] is a major receptor for dengue infection. DC-SIGN, also called CD209, expresses on dendritic cells (DCs) that bind to ICAM-3, which is expressed on T cells to facilitate the initial interaction between DCs and T cells. Variations in the CD209 promoter (−336 A/G; rs4804803) genotype are involved in the pathogenesis of human infectious diseases. Here we found that patients with dengue hemorrhagic fever (DHF) had a higher frequency of the AG or GG genotype of rs4804803 than DF or controls. Functional studies determined that monocyte-derived DCs (MDDCs) from individuals with AG genotype had significantly higher cell surface DC-SIGN expression, associated with higher TNFα, IL-12p40, and IP-10 production, but lower viral replication than those with AA genotype. An increase in DEN-2 replication in MDDCs was observed following the addition of anti-IP-10 neutralizing antibody. These findings highlight the fact that the rs4804803 SNP in the CD209 promoter is associated with DHF and correlated to DC-SIGN expression and immune augmentation

The relationship between preoperative American Society of Anesthesiologists Physical Status Classification scores and functional recovery following hip-fracture surgery

Abstract Background Little is known about the relationship of the American Society of Anesthesiologists Physical Status Classification scores (ASA scores) on patient outcomes following hip fracture surgery in Asian countries. Therefore, this study explored the association of patients’ preoperative ASA scores on trajectories of recovery in physical functioning and health outcomes during the first year following postoperative discharge for older adults with hip-fracture surgery in Taiwan. Methods The data for this study was generated from three prior studies. Participants (N = 226) were older hip-fracture patients from an observational study (n = 86) and two clinical trials (n = 61 and n = 79). Participants were recruited from the trauma wards of one medical center in northern Taiwan and data was collected prior to discharge and at 1, 3, 6, and 12 months after hospital discharge. Participants were grouped as ASA class 1–2 (50.5%; ASA Class 1, n = 7; ASA Class 2, n = 107) and ASA class 3 (49.5%, n = 112). Measures for mortality, service utilization, activities of daily living (ADL), measured by the Chinese Barthel Index, and health related quality of life, measured by Medical Outcomes Study Short Form-36, were assessed for the two groups. Generalized estimating equations (GEE) were used to analyze the changes over time for the two groups. Results During the first year following hip-fracture surgery, ASA class 1–2 participants had significantly fewer rehospitalizations (6%, p = .02) and better scores for mental health (mean = 70.29, standard deviation = 19.03) at 6- and 12-months following discharge than those classified as ASA 3. In addition, recovery of walking ability (70%, p = .001) and general health (adjusted mean = 58.31, p = .003) was also significantly better than ASA 3 participants. Conclusions There was a significant association of hip-fracture patients classified as ASA 1–2 with better recovery and service utilization during the first year following surgery. Interventions for hip fractured patients with high ASA scores should be developed to improve recovery and quality of life.https://deepblue.lib.umich.edu/bitstream/2027.42/138818/1/12891_2017_Article_1768.pd

Risk factors associated with symptomatic cholelithiasis in Taiwan: a population-based study

<p>Abstract</p> <p>Background</p> <p>Cholelithiasis has become a major health problem in Taiwan. The predominant type of gallstone found in Asian populations differs from that in the West, indicating possible differences in the etiology and risk factors for cholelithiasis. The aim of this study is to investigate the risk factors for cholelithiasis using data representative of the general population.</p> <p>Methods</p> <p>We performed a population-based, case-control study in which we analyzed medical data for 3725 patients newly diagnosed with cholelithiasis and 11175 gender- and age-matched controls with no history of cholelithiasis, using information obtained from the 2005 Registry for Beneficiaries of the National Health Insurance Research Database. Coexisting medical conditions were included in the analysis. Relative risks were estimated by adjusted odds ratio (OR) and 95% confidence interval (CI) using a multivariate logistic regression analysis.</p> <p>Results</p> <p>After controlling for the other covariates, multivariate logistic regression analysis identified the following as risk factors for cholelithiasis (in descending order of contribution): Among all patients - hepatitis C (OR = 2.78), cirrhosis (OR = 2.47), hepatitis B (OR = 2.00), obesity (OR = 1.89), and hyperlipidemia (OR = 1.54); Among women - hepatitis C (OR = 3.05), cirrhosis (OR = 1.92), obesity (OR = 1.91), menopause (OR = 1.61), hepatitis B (OR = 1.54), and hyperlipidemia (OR = 1.49). Diabetes mellitus appeared to have a marked influence on the development of cholelithiasis but was not identified as a significant independent risk factor for cholelithiasis.</p> <p>Conclusions</p> <p>The risk factors for cholelithiasis were obesity, hyperlipidemia, hepatitis B infection, hepatitis C infection, and cirrhosis in both genders, and menopause in females. Despite differences in the predominate type of gallstone in Asian versus Western populations, we identified no unique risk factors among the population of Taiwan.</p

COVID-19 Antibody Surveillance Among Healthcare Workers in A Non-COVID designated Cardiology Centre

BACKGROUND: Reports on healthcare worker antibody response to COVID-19 infection are scarce. We aim to determine theCOVID-19 antibody prevalence among healthcare workers in a cardiology centre and the relationship between case definitioncriteria with the COVID-19 antibody result. METHODS: Convenience sampling was applied. Healthcare workers in SarawakHeart Centre (SHC) cardiology, radiology, and emergency unit were recruited. A survey form on clinical symptoms and closecontact history was distributed. HEALGEN COVID-19 IgG/IgM rapid test was performed using serum/ whole blood specimen.Staff with positive COVID-19 antibody results were referred to the infectious disease specialist for assessment. RESULTS: Atotal of 310 staff were screened. 220(71%) were female, and the mean age was 36±7.7 years old. 46(14.8%) staff reported havingclinical symptoms at some stage from the end of January 2020 to the time of this surveillance. Number of staff who had a historyof overseas travel, close contact with confirmed COVID-19 patients, or had visited places with identified COVID-19 clusterswere 4(1.3%), 24(7.7%) and 24(7.7%) respectively. There were 14 staff (4.5%) with positive tests positive, 2 for IgM, and 12for IgG. All those with positive antibody were subsequently tested negative with RT-PCR test. The history of having clinicalsymptoms and exposure to COVID-19 cluster area were independently associated with a positive IgG result. CONCLUSION:The application of COVID-19 antibody serology rapid tests could determine true exposure of staff to the infection and allowus to reassess existing measures of infection control within the hospital

Clinical Outcomes and Predictors of Improved Left Ventricular Ejection Fraction in Heart Failure with Reduced Ejection Fraction due to Non-Ischemic Cardiomyopathy

Background: Left ventricular ejection fraction (LVEF) improvement is the cornerstone of LV reverse remodelling. It prognosticates heart failure with reduced ejection fraction (HFrEF). There is limited data on the clinical factors that predict LVEF improvement among non-ischemic cardiomyopathy (NICM) patients in Malaysia. Objective: To determine the 3-year outcomes and predictors of LVEF improvement in patients with (NICM) and HFrEF. Materials &amp; Methods: We recruited patients with NICM and HFrEF (LVEF &lt;40%) between 2016 and 2018. NICM was defined as HF with 1) normal coronary arteries or 2) any coronary artery stenosis not involving the proximal left anterior descending artery (LAD) and without transmural fibrosis in the LAD territory from cardiac magnetic resonance (CMR) imaging to account for the impaired LVEF. Clinical and imaging parameters were assessed using logistic regression statistics to determine the predictors of LVEF improvement. LVEF improvement is defined as a recovery of EF to &gt; 40% with at least a 10-point increment from baseline. The clinical outcomes at three year were 1) change in NYHA class and 2) composite of all-cause mortality, unscheduled clinic or emergency department visits, readmission and/or ventricular arrhythmia. Results: 43 patients were recruited. The mean duration of follow-up and echocardiographic assessment interval were 46 and 23 months, respectively. The cohort had a mean age of 46±13 years, and were mostly male (72%). More patients had NYHA 1 at the end of the study (37% vs 86%). 11 patients (25%) recorded composite outcomes. 62.8% had LVEF improvement. Patients with LVEF improvement had a lower incidence of late gadolinium enhancement (51.7% vs 85.7%, odds 5.6 ,p=0.045) and midwall fibrosis on CMR (18.5% vs 62.5%, odds 7.3, p=0.003). LVEF improvement did not affect the functional NYHA recovery (92% vs 81%, p=0.28). Patients with less LVEF improvement had higher incidence of composite outcome (18.5% vs 37.5%, p=0.168). Other characteristics were not significantly different between the groups. Conclusion: Patients with NICM and LVEF improvement had lower composite outcome. Absence of late gadolinium enhancement, particularly midwall fibrosis was an independant predictor of LVEF improvement. This underscores the importance of CMR tissue characterisation to refine the prognostication of NICM patients

Antitumor Effect of Malaria Parasite Infection in a Murine Lewis Lung Cancer Model through Induction of Innate and Adaptive Immunity

BACKGROUND: Lung cancer is the most common malignancy in humans and its high fatality means that no effective treatment is available. Developing new therapeutic strategies for lung cancer is urgently needed. Malaria has been reported to stimulate host immune responses, which are believed to be efficacious for combating some clinical cancers. This study is aimed to provide evidence that malaria parasite infection is therapeutic for lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: Antitumor effect of malaria infection was examined in both subcutaneously and intravenously implanted murine Lewis lung cancer (LLC) model. The results showed that malaria infection inhibited LLC growth and metastasis and prolonged the survival of tumor-bearing mice. Histological analysis of tumors from mice infected with malaria revealed that angiogenesis was inhibited, which correlated with increased terminal deoxynucleotidyl transferase-mediated (TUNEL) staining and decreased Ki-67 expression in tumors. Through natural killer (NK) cell cytotoxicity activity, cytokine assays, enzyme-linked immunospot assay, lymphocyte proliferation, and flow cytometry, we demonstrated that malaria infection provided anti-tumor effects by inducing both a potent anti-tumor innate immune response, including the secretion of IFN-γ and TNF-α and the activation of NK cells as well as adaptive anti-tumor immunity with increasing tumor-specific T-cell proliferation and cytolytic activity of CD8(+) T cells. Notably, tumor-bearing mice infected with the parasite developed long-lasting and effective tumor-specific immunity. Consequently, we found that malaria parasite infection could enhance the immune response of lung cancer DNA vaccine pcDNA3.1-hMUC1 and the combination produced a synergistic antitumor effect. CONCLUSIONS/SIGNIFICANCE: Malaria infection significantly suppresses LLC growth via induction of innate and adaptive antitumor responses in a mouse model. These data suggest that the malaria parasite may provide a novel strategy or therapeutic vaccine vector for anti-lung cancer immune-based therapy

Characterizing and Prognosticating Heart Failure with Improved Ejection Fraction Using NT-proBNP, Growth Differentiation Factor 15 and Global Longitudinal Strain

Background: Heart failure with improved ejection fraction (HFiEF) is a novel heart failure (HF) subgroup. There are sparse data on using NT-proBNP, growth differentiation factor 15 (GDF15) and global longitudinal strain (GLS) to characterize and prognosticate HFiEF patients. Objectives: (1) To determine the level and correlation between NT-proBNP, GDF-15 and GLS in HFiEF patients. (2) To examine the correlation of each marker with NYHA, MAGGIC prognostic score, HF etiologies, comorbidities status, degree of LVEF/ LV end-diastolic diameter change from baseline and diastolic dysfunction. (3) To look for association of each marker with follow-up LVEF change and 1-year composite mortality or HF events outcome. Materials & Methods: This was a cross-sectional observational study in Sarawak Heart Centre HF clinic. 53 HfiEF patients who had NT-proBNP and GDF15 tests performed were selected. This cohort had no HF events in the past 6 months during the blood tests. Clinical characteristics, echocardiography parameters, and 1-year composite clinical outcome were analyzed retrospectively. Results: The mean age of the cohort was 52 years old and 81% were male. The cohort was highly comorbid (hypertension 71%; diabetes 45.3%; AF 17.3%). Most of the patients (87%) were asymptomatic by NYHA (I) and low rate of composite outcome was observed, 5.7%. The mean NT-proBNP, GDF-15, GLS were 357 pg/ml, 1572 pg/ml, and -12.1% respectively. There were significant moderate correlation between GDF15 with NT-proBNP (r=0.414) and NT-proBNP with GLS (r=-0.351). Higher NT-proBNP and GDF15 levels were associated with poorer MAGGIC prognostic scores (r=0.549, 0.41 respectively). NT-proBNP was the only marker associated with a higher degree of LVEF improvement compare to baseline echocardiography. NT-proBNP was also related to severe diastolic echo parameters. Hypertension and diabetes were strongly associated with higher elevated GDF15 levels. The lower mean GLS level was significantly associated with the presence of composite outcome (-6.45% vs -12.47%, p=0.0). Patients with NT-proBNP levels below the median cutoff had favourable follow-up LVEF improvement (+9.73%, p=0.035). Conclusion: In our HFiEF study cohort, NT-proBNP best correlate and prognosticate future LV remodelling. GDF15 was closely related to systemic illnesses such as diabetes. The role of GLS in our HFiEF cohort remains uncertain