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.

Concurrent Olaparib and Radiation Therapy in Older Patients With Newly Diagnosed Glioblastoma: The Phase 1 Dose-Escalation PARADIGM Trial.

Purpose: Patients with glioblastoma who are older or have poor performance status (PS) experience particularly poor clinical outcomes. At the time of study initiation, these patients were treated with short-course radiation therapy (40 Gy in 15 fractions). Olaparib is an oral inhibitor of the DNA repair enzyme poly (ADP-ribose) polymerase (PARP) that is well tolerated as a single agent but exacerbates acute radiation toxicity in extracranial sites.

The Relationship Between Cardiac Troponin in People Hospitalised for Exacerbation of COPD and Major Adverse Cardiac Events (MACE) and COPD Readmissions.

Background: No single biomarker currently risk stratifies chronic obstructive pulmonary disease (COPD) patients at the time of an exacerbation, though previous studies have suggested that patients with elevated troponin at exacerbation have worse outcomes. This study evaluated the relationship between peak cardiac troponin and subsequent major adverse cardiac events (MACE) including all-cause mortality and COPD hospital readmission, among patients admitted with COPD exacerbation.

Methods: Data from five cross-regional hospitals in England were analysed using the National Institute of Health Research Health Informatics Collaborative (NIHR-HIC) acute coronary syndrome database (2008-2017).

Pre-diagnostic blood biomarkers for adult glioma.

Glioma is one of the most common malignant primary brain tumours in adults, of which, glioblastoma is the most prevalent and malignant entity. Glioma is often diagnosed at a later stage of disease progression, which means it is associated with significant mortality and morbidity. Therefore, there is a need for earlier diagnosis of these tumours, which would require sensitive and specific biomarkers.

Delphi panel for consensus on the optimal management of dabrafenib plus trametinib-related pyrexia in patients with melanoma.

Purpose: Dabrafenib and trametinib combination therapy (dab + tram) is indicated to treat BRAF V600 mutation-positive unresectable/metastatic melanoma and as adjuvant treatment for resected stage III disease. Dab + tram-related pyrexia may require early therapy discontinuation. A modified Delphi panel was conducted to develop consensus on the optimal management of dab + tram-related pyrexia in patients with melanoma.

Translational activators and mitoribosomal isoforms cooperate to mediate mRNA-specific translation in Schizosaccharomyces pombe mitochondria.

Mitochondrial mRNAs encode key subunits of the oxidative phosphorylation complexes that produce energy for the cell. In Saccharomyces cerevisiae, mitochondrial translation is under the control of translational activators, specific to each mRNA. In Schizosaccharomyces pombe, which more closely resembles the human system by its mitochondrial DNA structure and physiology, most translational activators appear to be either lacking, or recruited for post-translational functions.

Treating brain metastases in melanoma: What is the optimal CNS-directed and systemic management?

Treatments for melanoma have significantly advanced with the approval of targeted treatments against the BRAF/MEK pathway and immunotherapy in the form of checkpoint inhibitors. Studies have shown the effectiveness of these treatments against brain metastases. However, the optimum treatment strategy utilising CNS-directed treatments such as stereotactic radiosurgery (SRS) and neurosurgical resection is less clear.

Sequential immunotherapy in melanoma: is it a realistic alternative to dual immunotherapy?

The treatment of metastatic melanoma has been revolutionised with the emergence of checkpoint inhibitors. The combination of Ipilimumab and Nivolumab offers the longest overall survival but is considerably more toxic than single-agent therapy. For patients who received single-agent immunotherapy it is unclear whether second-line immunotherapy is efficacious or tolerable.

Influence of Different Connecting Rod Configurations on the Stability of the Ilizarov/TSF Frame: A Biomechanical Study.

Aim: The Ilizarov external fixator (IEF) is frequently used in trauma and elective orthopaedics. Many of its biomechanical variables (ring size, wire diameter, wire number, half pins vs wires, etc.) and their influence on stability and stiffness have been investigated.

Health-related quality of life in patients with fully resected BRAF mutation-positive melanoma receiving adjuvant vemurafenib.

Aim Of Study: The aim of the study was to assess the impact of treatment with adjuvant vemurafenib monotherapy on health-related quality of life (HRQOL) in patients with resected stage IIC-IIIC melanoma.

Methods: The phase 3 BRIM8 study (NCT01667419) randomised patients with BRAF mutation-positive resected stage IIC-IIIC melanoma to 960 mg of vemurafenib twice daily or matching placebo for 52 weeks (13 × 28-day cycles). Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) version 3 at baseline, cycle 1 (days 1, 15 and 22), cycle 2 (days 1 and 15), day 1 of every subsequent 4-week cycle, the end-of-treatment visit and each visit during the follow-up period.

What Can Be Done To Better Support Older Adults To Age Successfully In Their Homes And Communities?

The rapid growth of the US population ages seventy-five and older in the coming years will increase the need for housing that accommodates mobility limitations and helps connect residents with supportive services and opportunities for socialization. While expanding the supply of housing with services such as those provided by independent and assisted living facilities is needed, so too are greater supports to allow older adults with disabilities to age successfully in their homes and communities. These include financial support for modifications to the home, the delivery of supportive services in the home by both family and paid caregivers, and the expansion of housing options in communities where older adults live.

Adjuvant vemurafenib in resected, BRAF mutation-positive melanoma (BRIM8): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial.

Background: Systemic adjuvant treatment might mitigate the high risk of disease recurrence in patients with resected stage IIC-III melanoma. The BRIM8 study evaluated adjuvant vemurafenib monotherapy in patients with resected, BRAF mutation-positive melanoma.

Methods: BRIM8 was a phase 3, international, double-blind, randomised, placebo-controlled study that enrolled 498 adults (aged ≥18 years) with histologically confirmed stage IIC-IIIA-IIIB (cohort 1) or stage IIIC (cohort 2) BRAF mutation-positive melanoma that was fully resected.

Loss of Msp1p in Schizosaccharomyces pombe induces a ROS-dependent nuclear mutator phenotype that affects mitochondrial fission genes.

Mitochondria continually fuse and divide to dynamically adapt to changes in metabolism and stress. Mitochondrial dynamics are also required for mitochondrial DNA (mtDNA) integrity; however, the underlying reason is not known. In this study, we examined the link between mitochondrial fusion and mtDNA maintenance in Schizosaccharomyces pombe, which cannot survive without mtDNA, by screening for suppressors of the lethality induced by loss of the dynamin-related large GTPase Msp1p.

Ribosome recycling defects modify the balance between the synthesis and assembly of specific subunits of the oxidative phosphorylation complexes in yeast mitochondria.

Mitochondria have their own translation machinery that produces key subunits of the OXPHOS complexes. This machinery relies on the coordinated action of nuclear-encoded factors of bacterial origin that are well conserved between humans and yeast. In humans, mutations in these factors can cause diseases; in yeast, mutations abolishing mitochondrial translation destabilize the mitochondrial DNA.

Does the study of genetic interactions help predict the function of mitochondrial proteins in Saccharomyces cerevisiae?

Mitochondria are complex organelles of eukaryotic cells that contain their own genome, encoding key subunits of the respiratory complexes. The successive steps of mitochondrial gene expression are intimately linked, and are under the control of a large number of nuclear genes encoding factors that are imported into mitochondria. Investigating the relationships between these genes and their interaction networks, and whether they reveal direct or indirect partners, can shed light on their role in mitochondrial biogenesis, as well as identify new actors in this process.

Yeast PPR proteins, watchdogs of mitochondrial gene expression.

PPR proteins are a family of ubiquitous RNA-binding factors, found in all the Eukaryotic lineages, and are particularly numerous in higher plants. According to recent bioinformatic analyses, yeast genomes encode from 10 (in S. pombe) to 15 (in S.

Interactions between peptidyl tRNA hydrolase homologs and the ribosomal release factor Mrf1 in S. pombe mitochondria.

Mitochondrial translation synthesizes key subunits of the respiratory complexes. In Schizosaccharomyces pombe, strains lacking Mrf1, the mitochondrial stop codon recognition factor, are viable, suggesting that other factors can play a role in translation termination. S.

Outcomes following iodine-125 brachytherapy in patients with Gleason 7, intermediate risk prostate cancer: a population-based cohort study.

Background And Purpose: To evaluate outcome in patients with Gleason 7 prostate cancer treated with iodine-125 brachytherapy at the British Columbia Cancer Agency.

Materials And Methods: Between 20th July 1998 and 7th February 2006, 1500 patients underwent I-125 prostate brachytherapy without supplemental external beam radiation therapy. Of these, 439 had Gleason 7 disease; 362 had Gleason 3+4 and 77 had 4+3 disease.

Factors predictive of symptomatic radiation injury after linear accelerator-based stereotactic radiosurgery for intracerebral arteriovenous malformations.

Purpose: To investigate predictive factors in the development of symptomatic radiation injury after treatment with linear accelerator-based stereotactic radiosurgery for intracerebral arteriovenous malformations and relate the findings to the conclusions drawn by Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC).

Methods And Materials: Archived plans for 73 patients who were treated at the British Columbia Cancer Agency were studied. Actuarial estimates of freedom from radiation injury were calculated using the Kaplan-Meier method.

Biochemical control with radiotherapy improves overall survival in intermediate and high-risk prostate cancer patients who have an estimated 10-year overall survival of >90%.

Purpose: To identify subgroups of patients with carcinoma of the prostate treated with radical radiotherapy that have improved overall survival when disease is biochemically controlled.

Methods And Materials: A cohort of 1,060 prostate cancer patients treated with radical radiotherapy was divided into nine subgroups based on National Comprehensive Cancer Network risk category and estimated 10-year overall survival (eOS 10y) derived from the age adjusted Charlson Comorbidity Index. Patients with and without biochemical control were compared with respect to overall survival.

An in silico approach combined with in vivo experiments enables the identification of a new protein whose overexpression can compensate for specific respiratory defects in Saccharomyces cerevisiae.

Background: The mitochondrial inner membrane contains five large complexes that are essential for oxidative phosphorylation. Although the structure and the catalytic mechanisms of the respiratory complexes have been progressively established, their biogenesis is far from being fully understood. Very few complex III assembly factors have been identified so far.

Nucleocytoplasmic shuttling of Ssd1 defines the destiny of its bound mRNAs.

Mechanisms that control mRNA metabolism are critical for cell function, development and stress response. The Saccharomyces cerevisiae mRNA-binding protein Ssd1 has been implicated in mRNA processing, ageing, stress response and maintenance of cell integrity. Ssd1 is a substrate of the LATS/NDR tumour suppressor orthologue Cbk1 kinase.

A genome wide study in fission yeast reveals nine PPR proteins that regulate mitochondrial gene expression.

Pentatricopeptide repeat (PPR) proteins are particularly numerous in plant mitochondria and chloroplasts, where they are involved in different steps of RNA metabolism, probably due to the repeated 35 amino acid PPR motifs that are thought to mediate interactions with RNA. In non-photosynthetic eukaryotes only a handful of PPR proteins exist, for example the human LRPPRC, which is involved in a mitochondrial disease. We have conducted a systematic study of the PPR proteins in the fission yeast Schizosaccharomyces pombe and identified, in addition to the mitochondrial RNA polymerase, eight proteins all of which localized to the mitochondria, and showed some association with the membrane.