Metformin Use and Vitamin B12 Deficiency in People with Type 2 Diabetes. What Are the Risk Factors? A Mini-systematic Review.

Metformin is recommended as the first-line agent for the management of type 2 diabetes following lifestyle and dietary changes. The long-term use of metformin has been associated with vitamin B12 deficiency. The aim of this review is to investigate the effect of metformin on vitamin B12 levels and identify any risk factors.

Mapping MAiD Discordance: A Qualitative Analysis of the Factors Complicating MAiD Bereavement in Canada.

Medical assistance in dying (MAiD) is an evolving practice in Canada, with requests and outcomes increasing each year, and yet controversy is present-with a vast spectrum of ethical positions on its permissibility. International research indicates that family members who experience disagreement over their loved one's decision to have MAiD are less likely to be actively involved in supporting patients through the practical aspects of the dying process. Family members with passive involvement in the assisted dying process may also experience more significant moral dilemmas and challenging grief experiences than those who supported the decision.

Unacknowledged Pain and Disenfranchised Grief: A Narrative Analysis of Physical and Emotional Pain in Complex MAiD Bereavement Stories.

Background: Pain can influence an individual's choice to pursue medical assistance in dying (MAiD) and may also influence how family members experience that decision. Family conflict or discordance surrounding a loved one's MAiD decision can cause unique challenges affecting grief and bereavement, including disenfranchised grief. There is limited knowledge of how individuals with complex MAiD bereavement experiences describe the role of physical and emotional pain in their bereavement stories.

Late Effects of Chronic Low Dose Rate Total Body Irradiation on the Heart Proteome of ApoE Mice Resemble Premature Cardiac Ageing.

Recent epidemiologic studies support an association between chronic low-dose radiation exposure and the development of cardiovascular disease (CVD). The molecular mechanisms underlying the adverse effect of chronic low dose exposure are not fully understood. To address this issue, we have investigated changes in the heart proteome of ApoE deficient (ApoE) C57Bl/6 female mice chronically irradiated for 300 days at a very low dose rate (1 mGy/day) or at a low dose rate (20 mGy/day), resulting in cumulative whole-body doses of 0.

parkrun participation, impact and perceived social inclusion among runners/walkers and volunteers with mental health conditions.

Engagement in recreation can positively impact the physical and mental health of those experiencing mental health challenges; however, the impact of engaging in other aspects of such recreation, such as volunteering, remain largely unexplored in this population. Volunteering is known to have a wealth of health and wellbeing benefits among the general population; therefore, the impact of recreational-based volunteering for those with mental health conditions deserves to be explored. The current study sought to examine the health, social and wellbeing impacts of parkrun engagement among runners and volunteers living with a mental health condition.

Stroke Prevention and Treatment in People With Type 2 Diabetes: Is There a Role for GLP-1 (Glucagon-Like Peptide-1) Analogues?

Stroke is a leading cause of disability and death, and people with type 2 diabetes (T2D) have a greater risk of stroke and death or disability from stroke. The underlying pathophysiology associating stroke and T2D is complicated by the association of risk factors for stroke frequently seen in people with T2D. Treatments to reduce the excess risk of new-onset stroke or to improve outcomes in people with T2D following stroke would be of major clinical interest.

Eruptive melanocytic naevi following initiation of elexacaftor/ivacaftor/tezacaftor for cystic fibrosis.

A 29 year old woman with cystic fibrosis (CF) presented to CF clinic following the sudden development of over 200 pigmented naevi located predominately on the trunk and limbs 3 months after commencing elexacaftor/tezacaftor/ivacaftor, a novel triple-therapy CFTR modulator therapy for CF. Skin biopsy confirmed benign naevi and the clinical presentation was consistent with eruptive melanocytic naevi. Elexacaftor/tezacaftor/ivacaftor received marketing authorisation in August 2020 and this is the first report of associated naevi.

Atypical Lemierre's Syndrome. A Case Report and Review of Literature.

Lemierre's syndrome (LS) is a rare disease entity, which can be catastrophic if organism-directed treatment is not initiated early. Lemierre's syndrome is frequently caused by Fusobacterium infection which is frequently susceptible to clindamycin. Evidence suggests there is an increase in the incidence of cases of drug resistant Fusobacterium species.

Quantifying telomeric lncRNAs using PNA-labelled RNA-Flow FISH (RNA-Flow).

Here we present a method to detect and quantify long non-coding RNAs, in particular those related to telomeres. By coupling the specificity of a peptide nucleic acid (PNA) probe with flow cytometry we have quantified cellular levels of TERRA and TERC lncRNAs in culture cell lines and PBMCs. This easy-to-use method appointed RNA-Flow allows reliable lncRNA quantification with broad applications in basic research and clinical diagnostics.

The Chaperone Protein GRP78 Promotes Survival and Migration of Head and Neck Cancer After Direct Radiation Exposure and Extracellular Vesicle-Transfer.

Background And Purpose: Increased levels of the chaperone protein GRP78 have been implicated in poorer outcomes of cancer therapy. We have therefore explored the functional connection between the expression of GRP78 and the development of radioresistance and metastatic behavior in HNSCC.

Material And Methods: The association between gene expression of GRP78 and survival in HNSCC patients was examined using the TCGA database.

Combining HDAC and MEK Inhibitors with Radiation against Glioblastoma-Derived Spheres.

Glioblastoma stem-like cells (GSLCs) in glioblastoma limit effective treatment and promote therapeutic resistance and tumor recurrence. Using a combined radiation and drug-screening platform, we tested the combination of a histone deacetylase inhibitor (HDACi) and MAPK/ERK kinase inhibitor (MEKi) with radiation to predict the efficacy against GSLCs. To mimic a stem-like phenotype, glioblastoma-derived spheres were used and treated with a combination of HDACi (MS-275) and MEKi (TAK-733 or trametinib) with 4 Gy irradiation.

Activation of PPARα by Fenofibrate Attenuates the Effect of Local Heart High Dose Irradiation on the Mouse Cardiac Proteome.

Radiation-induced cardiovascular disease is associated with metabolic remodeling in the heart, mainly due to the inactivation of the transcription factor peroxisome proliferator-activated receptor alpha (PPARα), thereby inhibiting lipid metabolic enzymes. The objective of the present study was to investigate the potential protective effect of fenofibrate, a known agonist of PPARα on radiation-induced cardiac toxicity. To this end, we compared, for the first time, the cardiac proteome of fenofibrate- and placebo-treated mice 20 weeks after local heart irradiation (16 Gy) using label-free proteomics.

Answering questions in a co-created formative exam question bank improves summative exam performance, while students perceive benefits from answering, authoring, and peer discussion: A mixed methods analysis of PeerWise.

Multiple choice questions (MCQs) are a common form of assessment in medical schools and students seek opportunities to engage with formative assessment that reflects their summative exams. Formative assessment with feedback and active learning strategies improve student learning outcomes, but a challenge for educators, particularly those with large class sizes, is how to provide students with such opportunities without overburdening faculty. To address this, we enrolled medical students in the online learning platform PeerWise, which enables students to author and answer MCQs, rate the quality of other students' contributions as well as discuss content.

In vitro cellular and proteome assays identify Wnt pathway and CDKN2A-regulated senescence affected in mesenchymal stem cells from mice after a chronic LD gamma irradiation in utero.

Reliable data on the effects of chronic prenatal exposure to low dose (LD) of ionizing radiation in humans are missing. There are concerns about adverse long-term effects that may persist throughout postnatal life of the offspring. Due to their slow cell cycle kinetics and life-long residence time in the organism, mesenchymal stem cells (MSCs) are more susceptible to low level genotoxic stress caused by extrinsic multiple LD events.

Data-Independent Acquisition Proteomics Reveals Long-Term Biomarkers in the Serum of C57BL/6J Mice Following Local High-Dose Heart Irradiation.

Cardiotoxicity is a well-known adverse effect of radiation therapy. Measurable abnormalities in the heart function indicate advanced and often irreversible heart damage. Therefore, early detection of cardiac toxicity is necessary to delay and alleviate the development of the disease.

Quantitative Proteomic Analysis Using Formalin-Fixed, Paraffin-Embedded (FFPE) Human Cardiac Tissue.

Clinical tissue archives represent an invaluable source of biological information. Formalin-fixed, paraffin-embedded (FFPE) tissue can be used for retrospective investigation of biomarkers of diseases and prognosis.Recently, the number of studies using proteome profiling of samples from clinical archives has markedly increased.

Isolation of Proteins from Extracellular Vesicles (EVs) for Mass Spectrometry-Based Proteomic Analyses.

Extracellular vesicles (EVs) are freely circulating nano/micrometer-sized membrane-bound vesicles released by various cell types. Their cargo consists of proteins, lipids, metabolites, and different types of RNA molecules reflecting the origin of the secreting cell type or tissue. Since the EV cargo is constantly changing in response to pathological status or different environmental stressors, it has been extensively studied in the quest for biomarkers, especially in the cancer research.

MEK1 Inhibitor Combined with Irradiation Reduces Migration of Breast Cancer Cells Including miR-221 and ZEB1 EMT Marker Expression.

The miR-221 expression is dependent on the oncogenic RAS-RAF-MEK pathway activation and influences epithelial-to-mesenchymal transition (EMT). The Cancer Genome Atlas (TCGA) database analysis showed high gene significance for ZEB1 with EMT module analysis and miR-221 overexpression within the triple-negative breast cancer (TNBC) and HER2+ subgroups when compared to luminal A/B subgroups. EMT marker expression analysis after MEK1 (TAK-733) inhibitor treatment and irradiation was combined with miR-221 and ZEB1 expression analysis.

A Five-Year report on the conception and establishment of the MSc Radiation Biology at the Technical University of Munich.

Purpose: The MSc Radiation Biology course is a highly interdisciplinary degree program placing radiation biology at the interface between biology, medicine, and physics, as well as their associated technologies. The goal was to establish an internationally acknowledged program with diverse and heterogeneous student cohorts, who benefit from each other academically as well as culturally. We have completed a Five-Year evaluation of the program to assess our qualification profile and the further direction we want to take.

Radiation Response of Human Cardiac Endothelial Cells Reveals a Central Role of the cGAS-STING Pathway in the Development of Inflammation.

Radiation-induced inflammation leading to the permeability of the endothelial barrier may increase the risk of cardiovascular disease. The aim of this study was to investigate potential mechanisms in vitro at the level of the proteome in human coronary artery endothelial cells (HCECest2) that were exposed to radiation doses of 0, 0.25, 0.

The Coming of Age for Big Data in Systems Radiobiology, an Engineering Perspective.

As high-throughput approaches in biological and biomedical research are transforming the life sciences into information-driven disciplines, modern analytics platforms for big data have started to address the needs for efficient and systematic data analysis and interpretation. We observe that radiobiology is following this general trend, with -omics information providing unparalleled depth into the biomolecular mechanisms of radiation response-defined as systems radiobiology. We outline the design of computational frameworks and discuss the analysis of big data in low-dose ionizing radiation (LDIR) responses of the mammalian brain.