Effect of introduction of intermittently scanned continuous glucose monitoring on glycaemic control in individuals living with type 2 diabetes mellitus treated with non-insulin therapies-A randomised controlled trial.

Aims: This pilot randomised controlled trial aimed to evaluate the effect of introducing isCGM on glycaemic control and diabetes distress in individuals with T2DM receiving non-insulin therapies.

Materials And Methods: Forty adults with T2DM were randomised to either receive FreeStyle Libre 2 (Libre 2), an isCGM system, or FreeStyle Libre Pro iQ (Libre Pro) also known as 'blinded' CGM. Participants were followed for 12 weeks.

Patient Outcomes in Helicopter Emergency Medical Service Documentaries and on Air Ambulance Websites.

Background Helicopter emergency medical service (HEMS) documentaries attract millions of viewers, and publicly available patient stories on Air Ambulance websites are vital to raise awareness and funding for Air Ambulance charities in the United Kingdom (UK). Despite abundant research investigating how fictional programs and news outlets present patient health outcomes, there are no comprehensive studies that investigate how non-fictional HEMS documentaries or Air Ambulance websites present patient outcomes. The aim of this study is to capture the frequency of poor outcomes (mortality) in patients broadcasted on documentaries focusing on HEMS and the patient stories section of UK Air Ambulance websites.

International perspective on military exposure data sources, applications, and opportunities for collaboration.

Military personnel may be exposed to a range of hazards. The assessment, documentation and reporting of military exposure information are important steps to guide health protection, services, and research to support actively serving members and veterans. In 2021, a Working Group of researchers from veteran and defense administrations across the Five Eyes countries (Australia, Canada, New Zealand, the United Kingdom, and the United States) was established to examine large military exposure data sources available in each country, their applications, and opportunities to leverage information across administrations and internationally.

A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome: No Evidence of Benefit, Supported by Epidemiology and In Vitro Data.

Background: Men are more severely affected by COVID-19. Testosterone may influence SARS-CoV-2 infection and the immune response.

Objective: To clinically, epidemiologically, and experimentally evaluate the effect of antiandrogens on SARS-CoV-2 infection.

Interpretive voices: coproducing creative enquiry in the time of COVID-19.

Objectives: The objective of the study is the development of a virtual pilot of student and clinician creative enquiry during the COVID-19 pandemic lockdown.

Methods: Evaluation of the pilot was carried out by a student-staff team and included review of creative pieces submitted, their impact and team reflection, drawing on the differing perspectives of staff and students.

Results: A series of powerful creative enquiry texts have been published and presented from this pilot.

Protective Behaviors and Secondary Harms Resulting From Nonpharmaceutical Interventions During the COVID-19 Epidemic in South Africa: Multisite, Prospective Longitudinal Study.

Background: In March 2020, South Africa implemented strict nonpharmaceutical interventions (NPIs) to contain the spread of COVID-19. Over the subsequent 5 months, NPI policies were eased in stages according to a national strategy. COVID-19 spread throughout the country heterogeneously; the disease reached rural areas by July and case numbers peaked from July to August.

COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial.

Objectives: The main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalised for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the connection between androgen receptor signalling and expression of TMPRSS2, an enzyme important for SARS-CoV-2 host cell internalization.

Trial Design: Hospitalised COVID-19 patients will be randomised (2:1) to enzalutamide plus standard of care vs.

Quantification of Neutrophil Extracellular Traps Isolated From Mouse Tissues.

One of the most intriguing functions of neutrophils is the production of neutrophil extracellular traps (NETs), which are formed when neutrophils decondense their internal DNA and extrude it along with cytotoxic proteins in a web-like structure. This process allows neutrophils to trap and kill pathogens, and is also associated with multiple hematological and autoimmune conditions. Due to their rapid degradation, there are many challenges in accurately and specifically detecting and quantifying NETs.

Protective behaviours and secondary harms from non-pharmaceutical interventions during the COVID-19 epidemic in South Africa: a multisite prospective longitudinal study.

Background: In March 2020 South Africa implemented strict non-pharmaceutical interventions (NPIs) to contain Covid-19. Over the subsequent five months NPIs were eased in stages according to national strategy. Covid-19 spread throughout the country heterogeneously, reaching rural areas by July and peaking in July-August.

Making emergency responders visible: working-class responses to industrial disaster in 19th-century journalism and poetry.

Hidden beneath the ground in coalmines, or behind the walls of factories, injured bodies of workers have too often been overlooked. Using the 1842 Hartley Colliery disaster as a case study, this paper contrasts journalistic neglect with the ways in which working-class poets illuminated responses to large-scale injury. Often the greatest difficulty in industrial disaster was in securing access to trapped victims.

Medical student volunteering during COVID-19: lessons for future interprofessional practice.

Due to the unprecedented pressures on healthcare systems during the COVID-19 pandemic, many medical students internationally volunteered to assist in hospitals. In the United Kingdom, most students worked in roles similar to Healthcare Assistants: helping to support nurses in providing patient care. Although the current situation is exceptional, with medical students eager to contribute to the COVID-19 response, they have also gained valuable experience in interprofessional collaboration.

The Emerging Role of Neutrophil Granulocytes in Multiple Sclerosis.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with a strong autoimmune, neurodegenerative, and neuroinflammatory component. Most of the common disease modifying treatments (DMTs) for MS modulate the immune response targeting disease associated T and B cells and while none directly target neutrophils, several DMTs do impact their abundance or function. The role of neutrophils in MS remains unknown and research is ongoing to better understand the phenotype, function, and contribution of neutrophils to both disease onset and stage of disease.

Bioenergetics of acquired cisplatin resistant H1299 non-small cell lung cancer and P31 mesothelioma cells.

Acquired cisplatin resistance is a common feature of tumours following cancer treatment with cisplatin and also of non-small cell lung cancer (H1299) and mesothelioma (P31) cell lines exposed to cisplatin. To elucidate the cellular basis of acquired cisplatin resistance, a comprehensive bioenergetic analysis was undertaken. We demonstrate that cellular oxygen consumption was significantly decreased in cisplatin resistant cells and that the reduction was primarily due to reduced mitochondrial activity as a result of reduced mitochondrial abundance.

Identification of novel genetic variants in the mutational hotspot region 14 kb upstream of the LCT gene in a Mexican population.

Several polymorphic loci linked to lactase persistence (LP) have been described, all located in a small mutational hotspot region far upstream (∼14 kb) of the lactase (LCT) gene. One is typically found in Europeans, LCT -13910C > T, several others are found in East Africans and Arabs, e.g.

Heterozygous colon cancer-associated mutations of SAMHD1 have functional significance.

Even small variations in dNTP concentrations decrease DNA replication fidelity, and this observation prompted us to analyze genomic cancer data for mutations in enzymes involved in dNTP metabolism. We found that sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1), a deoxyribonucleoside triphosphate triphosphohydrolase that decreases dNTP pools, is frequently mutated in colon cancers, that these mutations negatively affect SAMHD1 activity, and that several SAMHD1 mutations are found in tumors with defective mismatch repair. We show that minor changes in dNTP pools in combination with inactivated mismatch repair dramatically increase mutation rates.

Genome-wide analysis of the specificity and mechanisms of replication infidelity driven by imbalanced dNTP pools.

The absolute and relative concentrations of the four dNTPs are key determinants of DNA replication fidelity, yet the consequences of altered dNTP pools on replication fidelity have not previously been investigated on a genome-wide scale. Here, we use deep sequencing to determine the types, rates and locations of uncorrected replication errors that accumulate in the nuclear genome of a mismatch repair-deficient diploid yeast strain with elevated dCTP and dTTP concentrations. These imbalanced dNTP pools promote replication errors in specific DNA sequence motifs suggesting increased misinsertion and increased mismatch extension at the expense of proofreading.

Measles Virus: Identification in the M Protein Primary Sequence of a Potential Molecular Marker for Subacute Sclerosing Panencephalitis.

Subacute Sclerosing Panencephalitis (SSPE), a rare lethal disease of children and young adults due to persistence of measles virus (MeV) in the brain, is caused by wild type (wt) MeV. Why MeV vaccine strains never cause SSPE is completely unknown. Hypothesizing that this phenotypic difference could potentially be represented by a molecular marker, we compared glycoprotein and matrix (M) genes from SSPE cases with those from the Moraten vaccine strain, searching for differential structural motifs.

Distinct roles for the p53-like transcription factor XprG and autophagy genes in the response to starvation.

Autophagy and autolysis are two cannibalistic pathways which allow filamentous fungi to obtain nutrients once environmental nutrient sources are exhausted. In Aspergillus nidulans, the effects of mutations in two key autophagy genes, atgA, the ATG1 ortholog, and atgH, the ATG8 ortholog, were compared with mutations in xprG, which encodes a transcriptional activator that plays a key role in autolysis. The anti-fungal drug rapamycin induces autophagy in a range of organisms.

Cangrelor inhibits the binding of the active metabolites of clopidogrel and prasugrel to P2Y12 receptors in vitro.

Cangrelor is a rapid-acting, direct-binding, and reversible P2Y12 antagonist which has been studied for use during percutaneous coronary intervention (PCI) in patients with or without pretreatment with an oral P2Y12 antagonist. As cangrelor is administered intravenously, it is necessary to switch to an oral P2Y12 antagonist following PCI, such as the thienopyridines clopidogrel, and prasugrel or the non-pyridine ticagrelor. Previous studies have suggested a negative pharmacodynamic interaction between cangrelor and thienopyridines.

Determination of deoxyribonucleoside triphosphate concentrations in yeast cells by strong anion-exchange high-performance liquid chromatography coupled with ultraviolet detection.

DNA polymerase assays are commonly used for the detection of deoxyribonucleoside triphosphates (dNTPs) in biological samples. For better specificity and accuracy, high-performance liquid chromatography (HPLC) methods have been developed for the analysis of the four dNTPs in complex samples. Here we describe a simple method using isocratic strong anion-exchange (SAX) chromatographic separation coupled with ultraviolet detection (UV) for the analysis of the four dNTPs in budding yeast Saccharomyces cerevisiae.

Increased and imbalanced dNTP pools symmetrically promote both leading and lagging strand replication infidelity.

The fidelity of DNA replication requires an appropriate balance of dNTPs, yet the nascent leading and lagging strands of the nuclear genome are primarily synthesized by replicases that differ in subunit composition, protein partnerships and biochemical properties, including fidelity. These facts pose the question of whether imbalanced dNTP pools differentially influence leading and lagging strand replication fidelity. Here we test this possibility by examining strand-specific replication infidelity driven by a mutation in yeast ribonucleotide reductase, rnr1-Y285A, that leads to elevated dTTP and dCTP concentrations.

Mutations in the H, F, or M Proteins Can Facilitate Resistance of Measles Virus to Neutralizing Human Anti-MV Sera.

Although there is currently no evidence of emerging strains of measles virus (MV) that can resist neutralization by the anti-MV antibodies present in vaccinees, certain mutations in circulating wt MV strains appear to reduce the efficacy of these antibodies. Moreover, it has been hypothesized that resistance to neutralization by such antibodies could allow MV to persist. In this study, we use a novel in vitro system to determine the molecular basis of MV's resistance to neutralization.