Theory of morphodynamic information processing: Linking sensing to behaviour.

The traditional understanding of brain function has predominantly focused on chemical and electrical processes. However, new research in fruit fly (Drosophila) binocular vision reveals ultrafast photomechanical photoreceptor movements significantly enhance information processing, thereby impacting a fly's perception of its environment and behaviour. The coding advantages resulting from these mechanical processes suggest that similar physical motion-based coding strategies may affect neural communication ubiquitously.

The first Australian uterus transplantation procedure: A result of a long-term Australian-Swedish research collaboration.

Aims: The aim is to report the results of Australia's first uterus transplantation (UTx).

Methods: Following long-standing collaboration between the Swedish and Australian teams, Human Research Ethics approval was obtained to perform six UTx procedures in a collaborative multi-site research study (Western Sydney Local District Health 2019/ETH13038), including Royal Hospital for Women, Prince of Wales Hospital, and Westmead Hospital in New Souh Wales. Surgeries were approved in both the live donor (LD) and deceased donor models in collaboration with the inaugural Swedish UTx team.

Myofilament Alterations Associated with Human R14del-Phospholamban Cardiomyopathy.

Phospholamban () is a major regulator of cardiac contractility, and human mutations in this gene give rise to inherited cardiomyopathies. The deletion of Arginine 14 is the most-prevalent cardiomyopathy-related mutation, and it has been linked to arrhythmogenesis and early death. Studies in -humanized mutant mice indicated an increased propensity to arrhythmias, but the underlying cellular mechanisms associated with R14del- cardiac dysfunction in the absence of any apparent structural remodeling remain unclear.

Isoform changes of action potential regulators in the ventricles of arrhythmogenic phospholamban-R14del humanized mouse hearts.

Arrhythmogenic cardiomyopathy (ACM) is characterized by life-threatening ventricular arrhythmias and sudden cardiac death and affects hundreds of thousands of patients worldwide. The deletion of Arginine 14 (p.R14del) in the phospholamban (PLN) gene has been implicated in the pathogenesis of ACM.

Sleep microstructure and clinical characteristics of patients with restless legs syndrome.

Study Objectives: Restless legs syndrome (RLS) is a sleep-related movement disorder, often accompanied by sleep disruption. Obstructive sleep apnea (OSA) has a controversial prevalence among patients with RLS. We evaluated the clinical and sleep features of patients who attended our sleep clinic considering RLS and OSA.

Aberrant PLN-R14del Protein Interactions Intensify SERCA2a Inhibition, Driving Impaired Ca Handling and Arrhythmogenesis.

Phospholamban (PLN), a key modulator of Ca-homeostasis, inhibits sarcoplasmic reticulum (SR) calcium-ATPase (SERCA2a) and regulates cardiac contractility. The human mutation R14del has been identified in arrhythmogenic cardiomyopathy patients worldwide and is currently extensively investigated. In search of the molecular mechanisms mediating the pathological phenotype, we examined PLN-R14del associations to known PLN-interacting partners.

Imaging Modalities for Early Detection of Pancreatic Cancer: Current State and Future Research Opportunities.

Pancreatic cancer, one of the most lethal malignancies, is increasing in incidence. While survival rates for many cancers have improved dramatically over the last 20 years, people with pancreatic cancer have persistently poor outcomes. Potential cure for pancreatic cancer involves surgical resection and adjuvant therapy.

Gene editing reverses arrhythmia susceptibility in humanized PLN-R14del mice: modelling a European cardiomyopathy with global impact.

Aims: A mutation in the phospholamban (PLN) gene, leading to deletion of Arg14 (R14del), has been associated with malignant arrhythmias and ventricular dilation. Identifying pre-symptomatic carriers with vulnerable myocardium is crucial because arrhythmia can result in sudden cardiac death, especially in young adults with PLN-R14del mutation. This study aimed at assessing the efficiency and efficacy of in vivo genome editing, using CRISPR/Cas9 and a cardiotropic adeno-associated virus-9 (AAV9), in improving cardiac function in young adult mice expressing the human PLN-R14del.

In-Depth Characterization of Sleep Patterns Among People with Insomnia During the Pandemic of COVID-19.

Background: The effects of the COVID-19 pandemic on sleep duration and insomnia have been well studied in different studies. However, there is no study available on the characteristics of insomnia during the pandemic. This study aimed to evaluate the characteristics of insomnia experienced by the general Iranian population during the COVID-19 pandemic.

Impaired Right Ventricular Calcium Cycling Is an Early Risk Factor in R14del-Phospholamban Arrhythmias.

The inherited mutation (R14del) in the calcium regulatory protein phospholamban (PLN) is linked to malignant ventricular arrhythmia with poor prognosis starting at adolescence. However, the underlying early mechanisms that may serve as prognostic factors remain elusive. This study generated humanized mice in which the endogenous gene was replaced with either human wild type or R14del-PLN and addressed the early molecular and cellular pathogenic mechanisms.

Music during flexible cystoscopy for pain and anxiety - a patient-blinded randomised control trial.

Objectives: To assess the role of music in reducing the pain and anxiety associated with flexible cystoscopy using a blinded trial design.

Patients And Methods: A patient-blinded randomised control trial of music during flexible cystoscopy was performed comparing the pain, measured by visual analogue scale (VAS), anxiety, measured by the State-Trait Anxiety Inventory (STAI), and vital signs of 109 patients across two public hospitals in New South Wales, Australia. The purpose and hypothesis of the study was concealed from patients until after results had been collected.

Does the Microenvironment Hold the Hidden Key for Functional Precision Medicine in Pancreatic Cancer?

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and no significant improvement in patient survival has been seen in the past three decades. Treatment options are limited and selection of chemotherapy in the clinic is usually based on the performance status of a patient rather than the biology of their disease. In recent years, research has attempted to unlock a personalised treatment strategy by identifying actionable molecular targets in tumour cells or using preclinical models to predict the effectiveness of chemotherapy.

Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma Determine Response to SLC7A11 Inhibition.

Cancer-associated fibroblasts (CAF) are major contributors to pancreatic ductal adenocarcinoma (PDAC) progression through protumor signaling and the generation of fibrosis, the latter of which creates a physical barrier to drugs. CAF inhibition is thus an ideal component of any therapeutic approach for PDAC. SLC7A11 is a cystine transporter that has been identified as a potential therapeutic target in PDAC cells.

Ex vivo culture of intact human patient derived pancreatic tumour tissue.

The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is attributed to the highly fibrotic stroma and complex multi-cellular microenvironment that is difficult to fully recapitulate in pre-clinical models. To fast-track translation of therapies and to inform personalised medicine, we aimed to develop a whole-tissue ex vivo explant model that maintains viability, 3D multicellular architecture, and microenvironmental cues of human pancreatic tumours. Patient-derived surgically-resected PDAC tissue was cut into 1-2 mm explants and cultured on gelatin sponges for 12 days.

Diabetes-related outcomes after pancreatic surgery.

Background: The development of pancreatogenic diabetes mellitus (PDM) is a common complication post-pancreatectomy; however, its prevalence has not been described in Australia. We aimed to describe the glycaemic status pre- and post-pancreatectomy, compare patients' clinical characteristics, group according to pre- and post-pancreatectomy diabetes mellitus (DM) status and identify predictors of post-operative PDM.

Methods: We retrospectively reviewed the medical records of patients admitted for pancreatic resection at a single institution from 2011 to 2017.

Phosphorylation of cardiac myosin-binding protein-C contributes to calcium homeostasis.

Cardiac myosin-binding protein-C (cMyBP-C) is highly phosphorylated under basal conditions. However, its phosphorylation level is decreased in individuals with heart failure. The necessity of cMyBP-C phosphorylation for proper contractile function is well-established, but the physiological and pathological consequences of decreased cMyBP-C phosphorylation in the heart are not clear.

The AGITG GAP Study: A Phase II Study of Perioperative Gemcitabine and Nab-Paclitaxel for Resectable Pancreas Cancer.

Background: While combination therapy with nab-paclitaxel/gemcitabine (nab-gem) is effective in pancreatic ductal adenocarcinoma (PDAC), its efficacy as perioperative chemotherapy is unknown. The primary objective of this multicenter, prospective, single-arm, phase II study was to determine whether neoadjuvant therapy with nab-gem was associated with higher complete resection rates (R0) in resectable PDAC, while the secondary objectives were to determine the utility of radiological assessment of response to preoperative chemotherapy and the safety and efficacy of nab-gem as perioperative therapy.

Methods: Patients were recruited from eight Australian sites, and 42 patients with radiologically defined resectable PDAC and an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled.

High negative predictive value of 68Ga PSMA PET-CT for local lymph node metastases in high risk primary prostate cancer with histopathological correlation.

Background: Current guidelines highlight the importance of accurate staging in the management and prognostication of high risk primary prostate cancer. Conventional radiologic imaging techniques are insufficient to reliably detect lymph node metastases in prostate cancer. Despite promising results, there is limited published data on the diagnostic accuracy of PSMA PET-CT to assess local nodal metastases prior to radical prostatectomy.

Identifying risk factors of cerebrovascular injuries following blunt mandible fracture; a retrospective study from a national data base.

Background: The purpose of this study was to determine the risk factors of cerebrovascular injury (CVI) in patients with blunt mandible fractures.

Methods: All patients who sustained a mandible fracture as a result of blunt force trauma from the 2012-2014 National Trauma Data Bank from the United State of America were included in the study. A CVI was noted as having occurred if there was an injury to the vertebral or carotid artery in the neck.

Phosphorylation of Hsp20 Promotes Fibrotic Remodeling and Heart Failure.

Cardiomyocyte-specific increases in phosphorylated Hsp20 (S16D-Hsp20) to levels similar to those observed in human failing hearts are associated with early fibrotic remodeling and depressed left ventricular function, symptoms which progress to heart failure and early death. The underlying mechanisms appear to involve translocation of phosphorylated Hsp20 to the nucleus and upregulation of interleukin (IL)-6, which subsequently activates cardiac fibroblasts in a paracrine fashion through transcription factor STAT3 signaling. Accordingly, treatment of S16D-Hsp20 mice with a rat anti-mouse IL-6 receptor monoclonal antibody (MR16-1) attenuated interstitial fibrosis and preserved cardiac function.

Multimodality treatment of oligometastatic anal squamous cell carcinoma: A case series and literature review.

Background And Objectives: There is limited evidence to guide the management of patients with oligometastatic anal squamous cell carcinoma (SCC). We aimed to address this question by reporting the outcome of SCC patients who were treated with organ-directed therapies at two large cancer centers.

Methods: Patients with advanced anal SCC who were treated with surgery, stereotactic radiotherapy, or radiofrequency ablation (RFA) with a curative intent from 2008 to 2017 were retrospectively identified from the institutional electronic patient records.