Telomeres are hypersensitive to the formation of the common oxidative lesion 8-oxoguanine (8oxoG), which impacts telomere stability and function. OGG1 and MUTYH glycosylases initiate base excision repair (BER) to remove 8oxoG or prevent mutation. Here, we show OGG1 loss or inhibition, or MUTYH loss, partially rescues telomeric 8oxoG-induced premature senescence and associated proinflammatory responses, while loss of both glycosylases causes a near complete rescue in human fibroblasts.
View Article and Find Full Text PDFMed Mycol Case Rep
December 2024
Refractory invasive fungal disease is a significant clinical problem, with high morbidity, mortality and costs. The complex causes of refractory infection include breakthrough infection due to antifungal resistance (both innate and acquired), suboptimal therapy and impaired immune responses in critically ill or immunocompromised patients. This case series details three reports on the identification and management of refractory fungal infections, two cases of azole resistance and one case of resistant candidiasis, highlighting the importance of accurate diagnosis, monitoring, implementation of biomarkers (serological markers, PCR), antifungal susceptibility testing and antifungal stewardship to optimise management and minimise risks of emergence of drug resistance.
View Article and Find Full Text PDFBackground: Hypertension is a key risk factor for death and disability, and blood pressure reduction is associated with significant reductions in cardiovascular risk. Large trials have shown that interventions including self-monitoring of blood pressure can reduce blood pressure but real-world data from wider implementation are lacking.
Aim: The self-monitoring and management service evaluation in primary care (SHIP) study will evaluate a novel digital intervention for hypertension management and medication titration platform ("Hypertension-Plus") that is currently undergoing initial implementation into primary care in several parts of the UK.
Objective: The control of energy balance involves neural circuits in the central nervous system, including AGRP neurons in the arcuate nucleus of the hypothalamus (ARC). AGRP neurons are crucial for energy balance and their increased activity during fasting is critical to promote feeding behavior. The activity of these neurons is influenced by multiple signals including those acting on G-protein coupled receptors (GPCR) activating different intracellular signaling pathways.
View Article and Find Full Text PDFHumans' sense of the passage of time is subjective and determined by psychophysiological responses to the environment. The passing of time has been perceived to significantly slow in stressful situations, such as accidents or virtual threats. The current study will explore distortions in the perception of passage of time when threat is simulated using virtual reality (VR).
View Article and Find Full Text PDFAntibodies targeting epitopes through germline-encoded motifs can be found in different individuals. While these public antibodies are often beneficial, they also pose hurdles for subdominant antibodies to emerge. Here, we use transgenic mice that reproduce the human IGHV1-6901 germline-encoded antibody response to the conserved stem epitope on group 1 hemagglutinin (HA) of influenza A virus to show that this germline-endowed response can be overridden by a subdominant yet cross-group reactive public antibody response.
View Article and Find Full Text PDFBackground: The emotional experiences of nursing students are linked to learning outcomes. Peer learning is a key component of nursing education and simulation. However, little is known about the emotions of students in the context of peer learning.
View Article and Find Full Text PDFJ Prim Health Care
September 2024
Introduction Best-practice guidelines recommend that patients are followed-up to check if they have recovered following a mild traumatic brain injury (mTBI) and to refer to concussion services, if needed. However, in New Zealand, rates of follow-up are low and access to concussion services can be delayed. Aim We aimed to improve rates of follow-up and access to concussion services for mTBI patients aged ≥8 years by the implementation of a supported health pathway and test its success.
View Article and Find Full Text PDFBackground: The Chain of Survival identifies the importance of early recognition of patients who are at imminent risk of out-of-hospital cardiac arrest. This research investigated the interaction between callers and call-takers during calls to the Emergency Medical Service; it specifically focussed on patients who were alive at the initiation of the EMS call, but who subsequently deteriorated into out-of-hospital cardiac arrest during the prehospital phase of care (i.e.
View Article and Find Full Text PDFBackground: Clinical evidence suggests that anemia exacerbates traumatic bleeding and worsens outcomes.
Objectives: To study the influence of iron deficiency anemia on traumatic bleeding, coagulopathy, and mortality.
Methods: C57BL/6J mice received an iron-deficient diet (8 weeks; ±1 mg intraperitoneal iron dextran 2 weeks before trauma).
Objective: To evaluate the rate of supraventricular tachycardia (SVT) termination between 6 mg and 12 mg initial adenosine doses.
Methods: This multi-center, retrospective cohort study evaluated patients presenting to the emergency department (ED) from January 1, 2020 to June 30, 2022 in SVT and received adenosine. The primary objective of the study is to compare the rate of SVT termination between adenosine 6 mg and 12 mg as documented on a formal electrocardiogram.
Background: Weight stigma refers to the social rejection, discrimination, and ideological devaluation of individuals because of body size and is a direct result of weight bias and anti-fat attitudes. Individuals with higher weight may be less likely to seek healthcare due to weight stigma, and if or when they do present for care, medical providers with weight bias may fail to provide high quality care. Little, however, is known about the intersectionality of weight stigma and perceptions of healthcare interactions as experienced by individuals who also binge eat.
View Article and Find Full Text PDFOzone (O ) inhalation triggers asthmatic airway hyperresponsiveness (AHR), but the mechanisms by which this occurs are unknown. Previously, we developed a murine model of dust mite, ragweed, and (DRA)-induced allergic lung inflammation followed by O exposure for mechanistic investigation. The present study used single cell RNA-sequencing for unbiased profiling of immune cells within the lungs of mice exposed to DRA, O , or DRA+O , to identify the components of the immune cell niche that contribute to AHR.
View Article and Find Full Text PDFObjective: Patients identifying as lesbian, gay, bisexual, transgender and/or queer/questioning (LGBTQ+) report significant disparities in cancer care and are disproportionally affected by a cancer diagnosis on a number of health-related indicators. This study aimed to explore uterine cancer (UC) care from the perspectives of LGBTQ+ patients and stakeholders, to identify this population's care needs, which have been underprioritised thus far.
Methods And Analysis: Qualitative interview data were collected from three cohorts of participants: LGBTQ+ UC patients, partners of UC patients and stakeholders who provide advocacy and/or support within the UC care pathway, including healthcare professionals (HCPs).
Background: Delays in intravenous thrombolysis (IVT) treatment for acute ischemic stroke decrease the benefit of treatment. Difficulties determining a patient's clinical eligibility for IVT is a frequent cause of treatment delays.
Objective: We aimed to assess the effectiveness of the "PROVIDENCE" datasheet, a pre- hospital assessment of contraindications for IVT use applied by emergency medical services personnel.
Purpose: To mitigate the B/B sensitivity of velocity-selective inversion (VSI) pulse trains for velocity-selective arterial spin labeling (VSASL) by implementing adiabatic refocusing. This approach aims to achieve artifact-free VSI-based perfusion imaging through single-pair label-control subtractions, reducing the need for the currently required four-pair dynamic phase-cycling (DPC) technique when using a velocity-insensitive control.
Methods: We introduce a Fourier-transform VSI (FT-VSI) train that incorporates sinc-modulated hard excitation pulses with MLEV-8-modulated adiabatic hyperbolic secant refocusing pairs.
Background: Collaboration and decision making among nursing students are essential competencies in nursing education. However, how students collaborate and make decisions in simulation is a complex phenomenon and not well understood. This study aimed to develop a framework that describes peer collaborative clinical decision making (PCCDM) among nursing students in simulation.
View Article and Find Full Text PDFBackground: Providing safety-netting advice (SNA) in out-of-hours primary care is a recognised standard of safe care but it is not known how frequently this occurs in practice.
Aim: Assess the frequency and type of SNA documented in out-of-hours primary care and explore factors associated with its presence.
Design And Setting: Retrospective cohort using the Birmingham Out-of-hours General Practice Research Database.