The mechanism of MYB transcriptional regulation by MLL-AF9 oncoprotein.

Acute leukaemias express high levels of MYB which are required for the initiation and maintenance of the disease. Inhibition of MYB expression or activity has been shown to suppress MLL-fusion oncoprotein-induced acute myeloid leukaemias (AML), which are among the most aggressive forms of AML, and indeed MYB transcription has been reported to be regulated by the MLL-AF9 oncoprotein. This highlights the importance of understanding the mechanism of MYB transcriptional regulation in these leukaemias.

The clinical significance of Mycobacterium triplex.

Objectives: Mycobacterium triplex is a slow-growing nontuberculous mycobacteria (NTM) and is a rare cause of human disease. The pathogenicity, natural history and spectrum of disease is unknown. The aim of this study was to review the clinical features, outcomes and drug susceptibility testing (DST) of all M.

NLRP3 is associated with coronary artery disease in Vietnam veterans.

Background: Previous studies have established that coronary artery disease is associated with excess inflammation. These studies have shown an elevation of both pro and anti-inflammatory cytokines in sufferers of coronary artery disease. There is increasing interest in the role played by the inflammasome Nod Like Receptor family pyrin domain containing 3 (NLRP3) in the aetiology of coronary artery disease.

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex.

DNA methylation from germline cells in veterans with PTSD.

In this study we investigated genome-wide sperm DNA methylation patterns in trauma-exposed Vietnam veterans. At the genome-wide level, we identified 3 CpG sites associated with PTSD in sperm including two intergenic and one CpG within the CCDC88C gene. Of those associated with PTSD in sperm at a nominal level, 1868 CpGs were also associated with PTSD in peripheral blood (5.

Comparison of Sleep Patterns in Vietnam Veterans With and Without Posttraumatic Stress Disorder Using Wrist Actigraphy.

Study Objectives: Disturbed sleep is a hallmark feature of posttraumatic stress disorder (PTSD). However, few studies have examined sleep objectively in individuals with PTSD compared to trauma-exposed controls. This study used wrist actigraphy to measure and compare sleep patterns in trauma-exposed Australian Vietnam veterans (VV) with and without PTSD.

Interleukin-33 / Cyclin D1 imbalance in severe liver steatosis predicts susceptibility to ischemia reperfusion injury.

Transplanting donor livers with severe macrosteatosis is associated with increased risk of primary non-function (PNF). The purpose of this study was to identify steatosis-driven biomarkers as a predisposition to severe liver damage and delayed recovery following ischemia reperfusion injury. Wistar rats were fed a methionine- and choline-deficient (MCD) diet for up to three weeks to achieve severe macrosteatosis (>90%).

pulmonary disease: individual patient data meta-analysis.

Treatment of pulmonary disease (MAB-PD), caused by subsp. , subsp. or subsp.

Differential BDNF methylation in combat exposed veterans and the association with exercise.

Brain-derived neurotrophic factor (BDNF) gene is associated with increased risk of posttraumatic stress disorder (PTSD) and plays a role in neuroplasticity, cognition and memory. BDNF has strong potential as a therapeutic target as studies have shown that antidepressants, electroconvulsive treatment and exercise modulate BDNF expression and methylation. In this study we examined the role of BDNF methylation and expression in PTSD and the implications of exercise in mediating these effects.

Exploring immunomodulation by endocrine changes in Lady Windermere syndrome.

Lung disease due to nontuberculous mycobacteria (NTM) occurs with disproportionate frequency in postmenopausal women with a unique phenotype and without clinically apparent predisposing factors. Dubbed 'Lady Windermere syndrome', the phenotype includes low body mass index (BMI), tall stature and higher than normal prevalence of scoliosis, pectus excavatum and mitral valve prolapse. Although the pathomechanism for susceptibility to NTM lung disease in these patients remains uncertain, it is likely to be multi-factorial.

The inflammasome NLRP12 is associated with both depression and coronary artery disease in Vietnam veterans.

Several studies have established that Major depressive disorder is associated with excess inflammation with an elevation of both pro and anti-inflammatory cytokines in major depressive disorder. In addition, individuals with major depressive disorder are at higher risk of developing coronary artery disease. The role of innate immunity and NFκB-mediated inflammation in depression and its increased association with coronary artery disease is yet to be fully elucidated.

Spotlight on Bortezomib: potential in the treatment of hepatocellular carcinoma.

Introduction: This study reviews the evidence for the use of Bortezomib (BZB), a first-in-class proteasome inhibitor in advanced Hepatocellular carcinoma (HCC). This review aims to delineate the role of BZB within the management of non-surgical and metastatic HCC, either as an alternative or as an adjunct to the current treatment paradigm.

Areas Covered: In addition to BZB pharmacology and mechanism of action, safety and tolerance profiles of the drug obtained from clinical trials are explored.

Synergistic and independent action of endogenous microRNAs 122a and 199a for post-transcriptional liver detargeting of gene vectors.

In hepatocellular carcinoma (HCC), which usually develops in a cirrhotic liver, treatments preserving normal liver function and viability are vitally important. Here, we utilise the differential expression of miRNAs 122a and 199a between normal hepatocytes and HCC to generate vectors harbouring their binding sites for hepatocyte detargeting. Using a reporter gene, we observed a synergistic detargeting of cells expressing both miRNAs as well as cells expressing either of the miRNAs; while expression was retained in HCC cells negative for both miRNA122a and miRNA199a.

Thermal Ablation of Mucosal Defect Margins Reduces Adenoma Recurrence After Colonic Endoscopic Mucosal Resection.

Background & Aims: Colorectal cancer (CRC) can be prevented by colonoscopy and polypectomy. Endoscopic mucosal resection (EMR) is performed to remove large laterally spreading colonic lesions that have a high risk of progression to CRC. Endoscopically invisible micro-adenomas at the margins of the EMR site might contribute to adenoma recurrence, which occurs in 15% to 30% of patients who undergo surveillance.

Evaluation of an equine-assisted therapy program for veterans who identify as 'wounded, injured or ill' and their partners.

The aim of this study was to evaluate outcomes of an equine-assisted therapy program for Defence Force veterans and their partners across the psychological domains of depression, anxiety, stress, posttraumatic stress, happiness, and quality of life, as well as compare the outcomes of an Individual and Couples program. A non-controlled, within-subjects longitudinal design was utilized with assessment at three time points (pre-intervention, post-intervention, and three months follow-up). Between-subjects analysis with two groups was also conducted to compare the outcomes of the Individual and Couples programs.

MicroRNA199a-Based Post-transcriptional Detargeting of Gene Vectors for Hepatocellular Carcinoma.

A gene therapeutic platform needs to be both efficient and safe. The criterion of safety is particularly important for diseases like hepatocellular carcinoma (HCC), which develop in a background of an already compromised liver. Gene vectors can be constructed either by targeting HCC or by detargeting liver and/or other major organs.

Amikacin Liposome Inhalation Suspension for Treatment-Refractory Lung Disease Caused by Complex (CONVERT). A Prospective, Open-Label, Randomized Study.

Improved therapeutic options are needed for patients with treatment-refractory nontuberculous mycobacterial lung disease caused by complex (MAC). To evaluate the efficacy and safety of daily amikacin liposome inhalation suspension (ALIS) added to standard guideline-based therapy (GBT) in patients with refractory MAC lung disease. Adults with amikacin-susceptible MAC lung disease and MAC-positive sputum cultures despite at least 6 months of stable GBT were randomly assigned (2:1) to receive ALIS with GBT (ALIS + GBT) or GBT alone.

Detailed Polysomnography in Australian Vietnam Veterans With and Without Posttraumatic Stress Disorder.

Study Objectives: Recent results from the PTSD Initiative, a cross-sectional cohort study in Australian Vietnam veterans (VV) with and without posttraumatic stress disorder (PTSD), demonstrated an increased prevalence of self-reported sleep disturbances in those with PTSD. This study aimed to objectively assess the prevalence of sleep disorders in the same cohort using detailed polysomnography (PSG).

Methods: Participants from the PTSD Initiative were recruited to undergo PSG.

The association between post-traumatic stress disorder and coronary artery disease: a meta-analysis.

Objectives: There are some psychosocial factors that have similar importance to biological factors in the genesis of coronary diseases. However, reasons for high rates of coronary heart disease in individuals with post-traumatic stress disorder (PTSD) are yet to be fully elucidated. Using a meta-analysis, we investigated the longitudinal relationship between PTSD and coronary heart disease (CHD) as an independent factor in the aetiology of CHD.

Monitoring Immune Checkpoint Regulators as Predictive Biomarkers in Hepatocellular Carcinoma.

The global burden of hepatocellular carcinoma (HCC), one of the frequent causes of cancer-related deaths worldwide, is rapidly increasing partly due to the limited treatment options available for this disease and recurrence due to therapy resistance. Immune checkpoint inhibitors that are proved to be beneficial in the treatment of advanced melanoma and other cancer types are currently in clinical trials in HCC. These ongoing trials are testing the efficacy and safety of a few select checkpoints in HCC.

Anomalies in T Cell Function Are Associated With Individuals at Risk of Complex Infection.

The increasing global incidence and prevalence of non-tuberculous mycobacteria (NTM) infection is of growing concern. New evidence of person-to-person transmission of multidrug-resistant NTM adds to the global concern. The reason why certain individuals are at risk of NTM infections is unknown.