Targeting Bromodomain and Extra-Terminal (BET) Family Proteins in Castration-Resistant Prostate Cancer (CRPC).

Persistent androgen receptor (AR) signaling drives castration-resistant prostate cancer (CRPC) and confers resistance to AR-targeting therapies. Novel therapeutic strategies to overcome this are urgently required. We evaluated how bromodomain and extra-terminal (BET) protein inhibitors (BETi) abrogate aberrant AR signaling in CRPC.

Regional variation in the characteristics, incidence and outcomes of out-of-hospital cardiac arrest in Australia and New Zealand: Results from the Aus-ROC Epistry.

Introduction: The aim of this study was to investigate regional variation in the characteristics, incidence and outcomes of out-of-hospital cardiac arrest (OHCA) in Australia and New Zealand.

Methods: This was a population-based cohort study of OHCA using data from the Aus-ROC Australian and New Zealand OHCA Epistry over the period of 01 January 2015-31 December 2015. Seven ambulance services contributed data to the Epistry with a capture population of 19.

is a driver of aggressive prostate cancer by promoting invasion, cell fate and cytoskeleton alterations and epithelial to mesenchymal transition.

Aggressive lethal prostate cancer is characterised by tumour invasion, metastasis and androgen resistance. Understanding the mechanisms by which localised disease progresses to advanced lethal stages is key to the development of effective therapies. Here we have identified a novel role for the transcription factor, SOX9, as a driver of aggressive invasive prostate cancer.

Prostate Organogenesis.

The prostate is a male exocrine gland that secretes components of the seminal fluid. In men, prostate tumors are one of the most prevalent cancers. Studies on the development of the prostate have given a better understanding of the processes and genes that are important in the formation of this organ and have provided insights into the mechanisms of prostate tumorigenesis.

Slow Magnetic Relaxation and Single-Molecule Toroidal Behaviour in a Family of Heptanuclear {Cr Ln } (Ln=Tb, Ho, Er) Complexes.

The synthesis, magnetic properties, and theoretical studies of three heterometallic {Cr Ln } (Ln=Tb, Ho, Er) complexes, each containing a metal topology consisting of two Ln triangles connected via a Cr linker, are reported. The {CrTb } and {CrEr } analogues display slow relaxation of magnetization in a 3000 Oe static magnetic field. Single-crystal measurements reveal opening up of the hysteresis loop for {CrTb } and {CrHo } molecules at low temperatures.

An audit of change in clinical practice: from oxygen-driven to air-driven nebulisers for prehospital patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).

Background: In developed countries, ambulances normally carry oxygen cylinders, but not compressed air. Treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with oxygen-driven nebulisers can result in hypercapnia and acidosis. Attempts to avoid this have involved interrupted administration of oxygen.

Adjuvants to local anesthetics: Current understanding and future trends.

Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by its duration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action.

Polycomb repressive complex 1 modifies transcription of active genes.

This study examines the role of Polycomb repressive complex 1 (PRC1) at active genes. The PRC1 and PRC2 complexes are crucial for epigenetic silencing during development of an organism. They are recruited to Polycomb response elements (PREs) and establish silenced domains over several kilobases.

Identification of Cancer-Targeted Tropomyosin Inhibitors and Their Synergy with Microtubule Drugs.

Actin filaments, with their associated tropomyosin polymers, and microtubules are dynamic cytoskeletal systems regulating numerous cell functions. While antimicrotubule drugs are well-established, antiactin drugs have been more elusive. We previously targeted actin in cancer cells by inhibiting the function of a tropomyosin isoform enriched in cancer cells, Tpm3.

CHD1 loss sensitizes prostate cancer to DNA damaging therapy by promoting error-prone double-strand break repair.

Background: Deletion of the chromatin remodeler chromodomain helicase DNA-binding protein 1 (CHD1) is a common genomic alteration found in human prostate cancers (PCas). CHD1 loss represents a distinct PCa subtype characterized by SPOP mutation and higher genomic instability. However, the role of CHD1 in PCa development in vivo and its clinical utility remain unclear.

Knowledge, attitudes, beliefs, and behaviors of university students, faculty, and staff during a meningococcal serogroup B outbreak vaccination program.

Objectives: During an outbreak of invasive meningococcal B disease on a university campus, we explored the knowledge, attitudes, beliefs, and behaviors of members of the university community in relation to the disease, the vaccine, and the vaccination program.

Design: All students, faculty and staff were invited by email to participate in a 71-item online survey, which was administered after completion of the mass clinics for the first and second doses of a meningococcal B vaccination program.

Results: A total of 404 individuals responded to the survey; 75.

Biochemical changes in the injured brain.

Brain metabolism is an energy intensive phenomenon involving a wide spectrum of chemical intermediaries. Various injury states have a detrimental effect on the biochemical processes involved in the homeostatic and electrophysiological properties of the brain. The biochemical markers of brain injury are a recent addition in the armamentarium of neuro-clinicians and are being increasingly used in the routine management of neuro-pathological entities such as traumatic brain injury, stroke, subarachnoid haemorrhage and intracranial space occupying lesions.

Genome-wide barcoded transposon screen for cancer drug sensitivity in haploid mouse embryonic stem cells.

We describe a screen for cellular response to drugs that makes use of haploid embryonic stem cells. We generated ten libraries of mutants with piggyBac gene trap transposon integrations, totalling approximately 100,000 mutant clones. Random barcode sequences were inserted into the transposon vector to allow the number of cells bearing each insertion to be measured by amplifying and sequencing the barcodes.

Healthcare Utilization and Expenditures Associated With Appropriate and Inappropriate Implantable Defibrillator Shocks.

Background: In patients with implantable cardioverter-defibrillators, healthcare utilization (HCU) and expenditures related to shocks have not been quantified.

Methods And Results: We performed a retrospective cohort study of patients with implantable cardioverter-defibrillators identified from commercial and Medicare supplemental claims databases linked to adjudicated shock events from remote monitoring data. A shock event was defined as ≥1 spontaneous shocks delivered by an implanted device.

Description of the ambulance services participating in the Aus-ROC Australian and New Zealand out-of-hospital cardiac arrest Epistry.

Objective: The present study aimed to describe and examine similarities and differences in the current service provision and resuscitation protocols of the ambulance services participating in the Aus-ROC Australian and New Zealand out-of-hospital cardiac arrest (OHCA) Epistry. Understanding these similarities and differences is important in identifying ambulance service factors that might explain regional variation in survival of OHCA in the Aus-ROC Epistry.

Methods: A structured questionnaire was completed by each of the ambulance services participating in the Aus-ROC Epistry.

Drosophila TDP-43 RNA-Binding Protein Facilitates Association of Sister Chromatid Cohesion Proteins with Genes, Enhancers and Polycomb Response Elements.

The cohesin protein complex mediates sister chromatid cohesion and participates in transcriptional control of genes that regulate growth and development. Substantial reduction of cohesin activity alters transcription of many genes without disrupting chromosome segregation. Drosophila Nipped-B protein loads cohesin onto chromosomes, and together Nipped-B and cohesin occupy essentially all active transcriptional enhancers and a large fraction of active genes.

Aryl Hydrocarbon Receptor Antagonist StemRegenin 1 Promotes the Expansion of Human Promyelocytic Leukemia Cell Line, NB4.

Background/aim: StemRegenin 1 (SR1), an antagonist of aryl hydrocarbon receptor (AHR), reportedly promotes expansion of hematopoietic stem cells but its effect on leukemia cells is unclear. This study focused on the role of SR1 in leukemia cell proliferation.

Materials And Methods: AHR expression was compared in the cell lines Jurkat, Kasumi-1, NB4 and K562, using real-time polymerase chain reaction.

Rapid surveillance for health events following a mass meningococcal B vaccine program in a university setting: A Canadian Immunization Research Network study.

An outbreak of Neisseria meningitidis serotype B infection occurred at a small residential university; public health announced an organizational vaccination program with the 4-component Meningococcal B (4CMenB) vaccine (Bexsero(TM), Novartis/GlaxoSmithKline Inc.) several days later. Since there were limited published data on reactogenicity of 4CMenB in persons over 17years of age, this study sought to conduct rapid surveillance of health events in vaccinees and controls using an online survey.

High-Level Clonal FGFR Amplification and Response to FGFR Inhibition in a Translational Clinical Trial.

Unlabelled: FGFR1 and FGFR2 are amplified in many tumor types, yet what determines response to FGFR inhibition in amplified cancers is unknown. In a translational clinical trial, we show that gastric cancers with high-level clonal FGFR2 amplification have a high response rate to the selective FGFR inhibitor AZD4547, whereas cancers with subclonal or low-level amplification did not respond. Using cell lines and patient-derived xenograft models, we show that high-level FGFR2 amplification initiates a distinct oncogene addiction phenotype, characterized by FGFR2-mediated transactivation of alternative receptor kinases, bringing PI3K/mTOR signaling under FGFR control.

Mechanical ventilation in neurological and neurosurgical patients.

Approximately 20% of all patients requiring mechanical ventilation suffer from neurological dysfunction. It is imperative in the ventilatory management of such patients to have a thorough understanding of the disease pathology that may require institution of mechanical ventilation as well as in realizing its effects on the injured brain. These patients have unique challenges pertaining to the assessment and securing of the airway, maintenance of mechanical ventilation, as well as weaning and extubation readiness.

Establishing the Aus-ROC Australian and New Zealand out-of-hospital cardiac arrest Epistry.

Introduction: Out-of-hospital cardiac arrest (OHCA) is a global health problem with low survival. Regional variation in survival has heightened interest in combining cardiac arrest registries to understand and improve OHCA outcomes. While individual OHCA registries exist in Australian and New Zealand ambulance services, until recently these registries have not been combined.

Out-of-hospital Cardiac Arrest Patient Characteristics: Comparing ventricular arrhythmia and Pulseless Electrical Activity.

Background: The proportion of patients suffering out-of-hospital cardiac arrest presenting with ventricular arrhythmias/ventricular fibrillation (VT/VF) is decreasing, while the proportion presenting with pulseless electrical activity (PEA) is increasing. Cardiac arrest interventions target VT/VF and survival rates from PEA are much lower. The aim of this study was to compare clinical characteristics of those suffering PEA and VT/VF.