Epidemiology, characteristics, and outcomes of patients with acute-on-chronic liver failure in Australia.

Background And Aim: Acute-on-chronic liver failure (ACLF) is distinct from acute decompensation (AD) of cirrhosis in its clinical presentation, pathophysiology, and prognosis. There are limited published Australian ACLF data.

Methods: We performed a single-center retrospective cohort study of all adults with cirrhosis admitted with a decompensating event to a liver transplantation (LT) centre between 2015 and 2020.

MELD-GRAIL and MELD-GRAIL-Na Are Not Superior to MELD or MELD-Na in Predicting Liver Transplant Waiting List Mortality at a Single-center Level.

Background: Controversy exists regarding the best predictive model of liver transplant waiting list (WL) mortality. Models for end-stage liver disease-glomerular filtration rate assessment in liver disease (MELD-GRAIL) and MELD-GRAIL-Na were recently described to provide better prognostication, particularly in females. We evaluated the performance of these scores compared to MELD and MELD-Na.

Narrow band imaging versus white light for detecting sessile serrated lesion: A prospective randomized multicenter study.

Objectives: Colonoscopy is the gold standard diagnostic test used to detect early colorectal lesions and prevent colorectal carcinoma. Narrow band imaging (NBI) is an imaging technique that provides improved image resolution of the mucosa during endoscopy. Whether NBI improves the detection of sessile serrated lesion (SSL) is controversial-our aim was to assess this during routine colonoscopy.

Electrophysiological and Structural Remodeling of the Atria in a Mouse Model of Troponin-I Mutation Linked Hypertrophic Cardiomyopathy: Implications for Atrial Fibrillation.

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disorder affecting one in 500 of the general population. Atrial fibrillation (AF) is the most common arrhythmia in patients with HCM. We sought to characterize the atrial electrophysiological and structural substrate in young and aging Gly203Ser cardiac troponin-I transgenic (HCM) mice.

The L-type Ca(2+) channel facilitates abnormal metabolic activity in the cTnI-G203S mouse model of hypertrophic cardiomyopathy.

Key Points: Genetic mutations in cardiac troponin I (cTnI) are associated with development of hypertrophic cardiomyopathy characterized by myocyte remodelling, disorganization of cytoskeletal proteins and altered energy metabolism. The L-type Ca(2+) channel is the main route for calcium influx and is crucial to cardiac excitation and contraction. The channel also regulates mitochondrial function in the heart by a functional communication between the channel and mitochondria via the cytoskeletal network.

The Role of the L-Type Ca Channel in Altered Metabolic Activity in a Murine Model of Hypertrophic Cardiomyopathy.

Heterozygous mice ( ) expressing the human disease-causing mutation exhibit cardinal features of hypertrophic cardiomyopathy (HCM) including hypertrophy, myocyte disarray, and increased myocardial fibrosis. Treatment of mice with the L-type calcium channel (I) antagonist diltiazem has been shown to decrease left ventricular anterior wall thickness, cardiac myocyte hypertrophy, disarray, and fibrosis. However, the role of the I in the development of HCM is not known.

Comparative transcriptome profiling in human bicuspid aortic valve disease using RNA sequencing.

Intrinsic valvular degeneration and dysfunction is the most common complication of bicuspid aortic valve (BAV) disease. Phenotypically, it ranges from calcific aortic stenosis to redundant or prolapsing regurgitant leaflets. The underlying molecular mechanism underpinning phenotype heterogeneity of valvular degeneration in BAV is poorly understood.

CCN2 plays a key role in extracellular matrix gene expression in severe hypertrophic cardiomyopathy and heart failure.

Hypertrophic cardiomyopathy (HCM) is the most common inherited primary myocardial disorder. HCM is characterized by interstitial fibrosis and excessive accumulation of extracellular matrix (ECM) proteins. Fibrosis in HCM has been associated with impaired cardiac function and heart failure, and has been considered a key substrate for ventricular arrhythmias and sudden death.

Global microRNA profiling of the mouse ventricles during development of severe hypertrophic cardiomyopathy and heart failure.

MicroRNAs (miRNAs) regulate post-transcriptional gene expression during development and disease. We have determined the miRNA expression levels of early- and end-stage hypertrophic cardiomyopathy (HCM) in a severe, transgenic mouse model of the disease. Five miRNAs were differentially expressed at an early stage of HCM development.

Respiratory distress and perinatal lethality in Nedd4-2-deficient mice.

The epithelial sodium channel (ENaC) is essential for sodium homoeostasis in many epithelia. ENaC activity is required for lung fluid clearance in newborn animals and for maintenance of blood volume and blood pressure in adults. In vitro studies show that the ubiquitin ligase Nedd4-2 ubiquitinates ENaC to regulate its cell surface expression.

Opposing actions of extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription 3 (STAT3) in regulating microtubule stabilization during cardiac hypertrophy.

Excessive proliferation and stabilization of the microtubule (MT) array in cardiac myocytes can accompany pathological cardiac hypertrophy, but the molecular control of these changes remains poorly characterized. In this study, we examined MT stabilization in two independent murine models of heart failure and revealed increases in the levels of post-translationally modified stable MTs, which were closely associated with STAT3 activation. To explore the molecular signaling events contributing to control of the cardiac MT network, we stimulated cardiac myocytes with an α-adrenergic agonist phenylephrine (PE), and observed increased tubulin content without changes in detyrosinated (glu-tubulin) stable MTs.

Differential protein expression profiling of myocardial tissue in a mouse model of hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetic disorder caused by mutations in genes encoding sarcomere proteins. The mechanisms involved in the development of cardiac hypertrophy and heart failure remain poorly understood. Global proteomic profiling was used to study the cardiac proteome of mice predisposed to developing HCM.

Adverse effects of high glucose and free fatty acid on cardiomyocytes are mediated by connective tissue growth factor.

Diabetic cardiomyopathy is characterized by interstitial fibrosis and cardiomyocyte hypertrophy and apoptosis. Also known as CCN2, connective tissue growth factor (CTGF) is implicated in the fibrosis; however, whether it contributes to cardiomyocytes changes and adverse effects of high glucose and lipids on these cells remains unknown. Hearts from streptozotocin-induced diabetic rats had elevated CTGF and changes of pathological myocardial hypertrophy, fibrosis, and cardiomyocyte apoptosis.

Impact of multiple gene mutations in determining the severity of cardiomyopathy and heart failure.

1. Familial hypertrophic cardiomyopathy (FHC) is a primary cardiac disorder characterized by myocardial hypertrophy that demonstrates substantial diversity in both genetic causes and clinical manifestations. 2.

Severe heart failure and early mortality in a double-mutation mouse model of familial hypertrophic cardiomyopathy.

Background: Familial hypertrophic cardiomyopathy (FHC) is characterized by genetic and clinical heterogeneity. Five percent of FHC families have 2 FHC-causing mutations, which results in earlier disease onset, increased cardiac dysfunction, and a higher incidence of sudden death events. These observations suggest a relationship between the number of gene mutations and phenotype severity in FHC.

Abnormal cardiac response to exercise in a murine model of familial hypertrophic cardiomyopathy.

Clinical outcome in familial hypertrophic cardiomyopathy (FHC) may be influenced by modifying factors such as exercise. Transgenic mice which overexpress the human disease-causing cTnI gene mutation, Gly203Ser (designated cTnI-G203S), develop all the characteristic phenotypic features of FHC. To study the modifying effect of exercise in early disease, mice underwent swimming exercise at an early age prior to the development of the FHC phenotype.

Molecular insights from a novel cardiac troponin I mouse model of familial hypertrophic cardiomyopathy.

Gene mutations in cardiac troponin I (cTnI) account for up to 5% of genotyped families with familial hypertrophic cardiomyopathy (FHC). Little is known about how cTnI mutations cause disease. Five lines of transgenic mice were generated which overexpress the human disease-causing cTnI gene mutation, Gly203Ser (designated cTnI-G203S), in a cardiac-specific manner.

Genes, calcium and modifying factors in hypertrophic cardiomyopathy.

1. Familial hypertrophic cardiomyopathy (FHC) is a primary disorder of the myocardium characterized by remarkable diversity in clinical presentations, ranging from no symptoms to severe heart failure and sudden cardiac death. 2.

Cardiac troponin I mutations in Australian families with hypertrophic cardiomyopathy: clinical, genetic and functional consequences.

Background: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disorder caused by mutations in sarcomeric proteins. Cardiac troponin I (cTnI) is a key switch molecule in the sarcomere. Mutations in cTnI have been identified in <1% of genotyped HCM families.

Hypertrophic cardiomyopathy: from gene defect to clinical disease.

Major advances have been made over the last decade in our understanding of the molecular basis of several cardiac conditions. Hypertrophic cardiomyopathy (HCM) was the first cardiac disorder in which a genetic basis was identified and as such, has acted as a paradigm for the study of an inherited cardiac disorder. HCM can result in clinical symptoms ranging from no symptoms to severe heart failure and premature sudden death.