CAG-expansion mutation results in a dominant negative effect.

Huntington's disease (HD) remains an incurable and fatal neurodegenerative disease long after CAG-expansion mutation in the huntingtin gene () was identified as the cause. The underlying pathological mechanism, whether loss of function or gain of toxicity results from mutation, remains a matter of debate. In this study, we genetically modulated wild-type or mutant expression levels in isogenic human embryonic stem cells to systematically investigate their contribution to HD-specific phenotypes.

Automated conduction velocity estimation based on isochronal activation of heart chambers.

Background: Spatial differences in conduction velocity (CV) are critical for cardiac arrhythmias induction. We propose a method for an automated CV calculation to identify areas of slower conduction during cardiac arrhythmias and sinus rhythm.

Methods: Color-coded representations of the isochronal activation map using data coming from the RHYTHMIA™ Mapping System were reproduced by applying a temporal isochronal window at 20 ms.

Role of YAP in early ectodermal specification and a Huntington's Disease model of human neurulation.

The Hippo pathway, a highly conserved signaling cascade that functions as an integrator of molecular signals and biophysical states, ultimately impinges upon the transcription coactivator Yes-associated protein 1 (YAP). Hippo-YAP signaling has been shown to play key roles both at the early embryonic stages of implantation and gastrulation, and later during neurogenesis. To explore YAP's potential role in neurulation, we used self-organizing neuruloids grown from human embryonic stem cells on micropatterned substrates.

Alteplase Dose Assessment for Pleural infection Therapy (ADAPT) Study-2: Use of 2.5 mg alteplase as a starting intrapleural dose.

Background And Objective: Intrapleural tissue plasminogen activator/deoxyribonuclease (tPA/DNase) therapy is increasingly used in pleural infection. Bleeding risks and costs associated with tPA remain the clinical concerns. Our dose de-escalation series aims to establish the lowest effective dosing regimen for tPA/DNase.

The optimal timing of FDG-PET/CT in non-small cell lung cancer diagnosis and staging in an Australian centre.

Background: Clinical practice guidelines and re-imbursement schedules vary in the recommended timing of FDG-PET/CT in the diagnostic evaluation of suspected or confirmed lung cancer. The aim was to estimate the probability of requiring more than one invasive test to complete diagnosis and staging in non-small cell lung cancer if FDG-PET/CT was used prior to initial biopsy (FDG-PET/CT First) compared to current Australian funding criteria (CT First).

Methods: Single-centre retrospective study of individuals with pathologically confirmed NSCLC without evidence of metastatic disease on baseline computed tomography (CT) of the chest.

Midland non-invasive ventilation score: a tool to predict non-invasive ventilation failure in people with acute hypercapnic respiratory failure.

Use of non-invasive ventilation (NIV) in patients with hypercapnic respiratory failure has clear benefits over invasive ventilation. Existing risk prediction models are complex and difficult to apply in the acute setting. We developed the Midland NIV score comprising only five parameters for use to predict NIV failure (in-hospital death or intubation) at initiation.

Prospective validation of the RAPID clinical risk prediction score in adult patients with pleural infection: the PILOT study.

Background: Over 30% of adult patients with pleural infection either die and/or require surgery. There is no robust means of predicting at baseline presentation which patients will suffer a poor clinical outcome. A validated risk prediction score would allow early identification of high-risk patients, potentially directing more aggressive treatment thereafter.

Australia-wide cross-sectional survey of general practitioners' knowledge and practice of lung cancer screening.

Background: Low-dose computed tomography (LDCT) screening can reduce lung cancer deaths in high-risk individuals, yet current Australian guidelines do not recommend screening. Little is known about current screening practices in Australia.

Aim: To evaluate the proportion of general practitioners who report ordering lung cancer screening for their patients, identify factors associated with ordering lung cancer screening and assess general practitioners (GP) rationale for recommending screening and preference of composition of any future national targeted screening programme.

The impact of perceived risk, screening eligibility and worry on preference for lung cancer screening: a cross-sectional survey.

Lung cancer screening is effective at reducing lung cancer deaths when individuals at greatest risk are screened. Recruitment initiatives target all current and former smokers, of whom only some are eligible for screening, potentially leading to discordance between screening preference and eligibility in ineligible individuals. The objective of the present study was to identify factors associated with preference for screening among ever-smokers.

Middle-term Outcomes of Gatekeeper Implantation for Fecal Incontinence.

Background: Intersphincteric injectable bulking agents are one of the current treatment options for fecal incontinence, failing behavioral and medical therapy. Gatekeeper showed promising short-term results, but long-term outcomes are unknown.

Objective: The purpose of this study was to clinically evaluate a prospective cohort of fecal incontinence patients up to 36 months after implantation of Gatekeeper.

MeCP2 nuclear dynamics in live neurons results from low and high affinity chromatin interactions.

Methyl-CpG-binding-Protein 2 (MeCP2) is an abundant nuclear protein highly enriched in neurons. Here we report live-cell single-molecule imaging studies of the kinetic features of mouse MeCP2 at high spatial-temporal resolution. MeCP2 displays dynamic features that are distinct from both highly mobile transcription factors and immobile histones.

Toxoplasma gondii-associated cholecystitis in a cat receiving immunosuppressive treatment.

A 9-year-old female neutered domestic shorthair cat diagnosed with immune-mediated thrombocytopenia that was treated with prednisolone and cyclosporine, was presented for anorexia, vomiting, increased liver enzymes, and hyperbilirubinemia. Abdominal ultrasound revealed a markedly thickened gallbladder and common bile duct wall. Bile cytology detected severe neutrophilic inflammation and protozoal zoites.

Detection of multidrug resistance and extended-spectrum/plasmid-mediated AmpC beta-lactamase genes in Enterobacteriaceae isolates from diseased cats in Italy.

Objectives: The aim of this study was to determine the antimicrobial susceptibility of Enterobacteriaceae isolated from cats affected by diseases commonly encountered in practice, and to characterise the third-generation cephalosporin (3GC)-resistance molecular mechanisms involved.

Methods: Clinical samples (n = 100) included 58 rectal swabs from cats with diarrhoea, 31 nasal swabs from cats with clinical signs of upper respiratory tract disease, four ear swabs from cats with otitis, three conjunctival swabs from cats with conjunctivitis, two oral swabs from cats with stomatitis, one swab from a skin abscess and one urine sample from a cat with cystitis. A total of 125 Enterobacteriaceae were isolated from 90 cats.

External validation of the SAPS3-CNIV score to predict hospital mortality following noninvasive ventilation: a retrospective single-centre study.

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Development and evaluation of a consumer information resource, including Patient Decision Aid, for lung cancer screening: a quasi-experimental study.

Lung cancer screening of high-risk individuals with computed tomography is a promising intervention to reduce lung cancer mortality. Patient Decision Aids (PtDAs) may assist eligible individuals assess the risks and benefits associated with screening. Screening preference is high among lower-risk, screening-ineligible individuals and strategies are needed to reduce screening demand among this group.

Spatial Orientation and Directional Judgments in Pilots vs. Nonpilots.

Background: Reading a map requires the ability to judge one's position in a large-scale space from information presented in a small-scale representation. Individuals are more accurate and faster in making judgments when the "up" direction on the map is the same as the "forward" direction of the environment, which is when a map is aligned with the perspective of the spatial layout they have learned (alignment effect). The aim of this study was to explore whether military pilots, who have high spatial abilities, would not show the alignment effect compared with nonpilots.

Current lung cancer screening practice amongst general practitioners in Western Australia: a cross-sectional study.

Lung cancer screening with low dose computed tomography (LDCT) is recommended in the USA and Canada for high-risk smokers but not in Australia. We administered a cross-sectional survey to Western Australian general practitioners (GP). The majority (64/93, 69%) reported requesting a screening chest X-ray (42/93, 45%) and/or LDCT (38/93, 41%) in the past year.

Effect of an Indwelling Pleural Catheter vs Talc Pleurodesis on Hospitalization Days in Patients With Malignant Pleural Effusion: The AMPLE Randomized Clinical Trial.

Importance: Indwelling pleural catheter and talc pleurodesis are established treatments for malignant pleural effusions among patients with poor prognosis.

Objective: To determine whether indwelling pleural catheters are more effective than talc pleurodesis in reducing total hospitalization days in the remaining lifespan of patients with malignant pleural effusion.

Design, Setting, And Participants: This open-label, randomized clinical trial included participants recruited from 9 centers in Australia, New Zealand, Singapore, and Hong Kong between July 2012 and October 2014; they were followed up for 12 months (study end date: October 16, 2015).

Dose De-escalation of Intrapleural Tissue Plasminogen Activator Therapy for Pleural Infection. The Alteplase Dose Assessment for Pleural Infection Therapy Project.

Rationale: Intrapleural therapy with a combination of tissue plasminogen activator (tPA) 10 mg and DNase 5 mg administered twice daily has been shown in randomized and open-label studies to successfully manage over 90% of patients with pleural infection without surgery. Potential bleeding risks associated with intrapleural tPA and its costs remain important concerns. The aim of the ongoing Alteplase Dose Assessment for Pleural infection Therapy (ADAPT) project is to investigate the efficacy and safety of dose de-escalation for intrapleural tPA.

Clostridium difficile infection in cystic fibrosis: an uncommon but life-threatening complication.

Adults with cystic fibrosis (CF) have significant rates of asymptomatic Clostridium difficile carriage and are frequently exposed to risk factors for C. difficile infection (CDI). Despite this, the rate of reported CDI in CF is low.

Antimicrobial resistance patterns of Enterobacteriaceae in European wild bird species admitted in a wildlife rescue centre.

Wild birds have been considered to be reservoirs of enteric human pathogens and vectors of resistance dissemination to the environment. During annual migration, they potentially play a role in the epidemiology of human associated zoonoses. The aim of this study was to investigate the frequency of isolation and antimicrobial susceptibility profiles of Enterobacteriaceae members isolated from cloacal swabs of common European wild birds.