Changes in the investigation and management of suspected myocardial infarction and injury during COVID-19: a multi-centre study using routinely collected healthcare data.

Objective: The COVID-19 pandemic was associated with a reduction in the incidence of myocardial infarction (MI) diagnosis, in part because patients were less likely to present to hospital. Whether changes in clinical decision making with respect to the investigation and management of patients with suspected MI also contributed to this phenomenon is unknown. Methods: Multicentre retrospective cohort study in three UK centres contributing data to the National Institute for Health Research Health Informatics Collaborative. Patients presenting to the Emergency Department (ED) of these centres between 1st January 2020 and 1st September 2020 were included. Three time epochs within this period were defined based on the course of the first wave of the COVID-19 pandemic: pre-pandemic (epoch 1), lockdown (epoch 2), post-lockdown (epoch 3). Results: During the study period, 10,670 unique patients attended the ED with chest pain or dyspnoea, of whom 6,928 were admitted. Despite fewer total ED attendances in epoch 2, patient presentations with dyspnoea were increased (p < 0.001), with greater likelihood of troponin testing in both chest pain (p = 0.001) and dyspnoea (p < 0.001). There was a dramatic reduction in elective and emergency cardiac procedures (both p < 0.001), and greater overall mortality of patients (p < 0.001), compared to the pre-pandemic period. Positive COVID-19 and/or troponin test results were associated with increased mortality (p < 0.001), though the temporal risk profile differed. Conclusions: The first wave of the COVID-19 pandemic was associated with significant changes not just in presentation, but also the investigation, management, and outcomes of patients presenting with suspected myocardial injury or MI.

Role of Senataxin in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive, uncurable neurodegenerative disorder characterized by the degradation of motor neurons leading to muscle impairment, failure, and death. Senataxin, encoded by the SETX gene, is a human helicase protein whose mutations have been linked with ALS onset, particularly in its juvenile ALS4 form. Using senataxin's yeast homolog Sen1 as a model for study, it is suggested that senataxin's N-terminus interacts with RNA polymerase II, whilst its C-terminus engages in helicase activity. Senataxin is heavily involved in transcription regulation, termination, and R-loop resolution, enabled by recruitment and interactions with enzymes such as ubiquitin protein ligase SAN1 and ribonuclease H (RNase H). Senataxin also engages in DNA damage response (DDR), primarily interacting with the exosome subunit Rrp45. The Sen1 mutation E1597K, alongside the L389S and R2136H gain-of-function mutations to senataxin, is shown to cause negative structural and thus functional effects to the protein, thus contributing to a disruption in WT functions, motor neuron (MN) degeneration, and the manifestation of ALS clinical symptoms. This review corroborates and summarizes published papers concerning the structure and function of senataxin as well as the effects of their mutations in ALS pathology in order to compile current knowledge and provide a reference for future research. The findings compiled in this review are indicative of the experimental and therapeutic potential of senataxin and its mutations as a target in future ALS treatment/cure discovery, with some potential therapeutic routes also being discussed in the review.

A metadata-aware application for remote scoring and exchange of tissue microarray images.

BACKGROUND: The use of tissue microarrays (TMA) and advances in digital scanning microscopy has enabled the collection of thousands of tissue images. There is a need for software tools to annotate, query and share this data amongst researchers in different physical locations. RESULTS: We have developed an open source web-based application for remote scoring of TMA images, which exploits the value of Microsoft Silverlight Deep Zoom to provide a intuitive interface for zooming and panning around digital images. We use and extend existing XML-based standards to ensure that the data collected can be archived and that our system is interoperable with other standards-compliant systems. CONCLUSION: The application has been used for multi-centre scoring of TMA slides composed of tissues from several Phase III breast cancer trials and ten different studies participating in the International Breast Cancer Association Consortium (BCAC). The system has enabled researchers to simultaneously score large collections of TMA and export the standardised data to integrate with pathological and clinical outcome data, thereby facilitating biomarker discovery.