Epilepsy is a neurological condition characterised by recurrent and persistent seizures. For paediatric patients, achieving early seizure freedom can have positive impacts on cognition, development, social integration and mental health, leading to improved quality of life. In general, one third of patients with epilepsy are refractory to medication; for these patients, epilepsy surgery may offer the only chance for improved seizure control.
View Article and Find Full Text PDFPersons experiencing homelessness (PEH) are at heightened risk for infection, morbidity, and mortality from COVID-19. However, health consequences of the pandemic extend far beyond those directly caused by the virus. This scoping review aimed to explore the impacts of the COVID-19 pandemic on the health and well-being of PEH in North America and Europe.
View Article and Find Full Text PDFAim Nutrition is the leading cause of chronic disease globally, yet it is unknown how much nutritional education GP trainees receive. The aim is to identify GP trainee attitudes to nutrition and compare with the programme directors who deliver this training. Methods A multicentre online survey questionnaire of 542 GP trainees in Ireland and 63 programme directors over 2 weeks in September 2019.
View Article and Find Full Text PDFThe central site(s) mediating the cardiovascular actions of the apelin-apelin receptor (APJ) system remains a major question. We hypothesized that the sensory circumventricular organs (CVOs), interfacing between the circulation and deeper brain structures, are sites where circulating apelin acts as a signal in the central nervous system to decrease blood pressure (BP). We show that APJ gene () expression was elevated in the CVOs of spontaneously hypertensive rats (SHRs) compared to normotensive Wistar Kyoto (WKY) controls, and that there was a greater mean arterial BP (MABP) decrease following microinjection of [Pyr]apelin-13 to the CVOs of SHRs compared to WKY rats.
View Article and Find Full Text PDFBackground: People experiencing homelessness have poor health indices and poor access to health care. Their health service utilisation (HSU) is typified by: late illness presentations; poor attendance rates at appointments; low usage of primary care services and outpatient departments; and high utilisation of emergency departments and inpatient services. Why people experiencing homelessness have these particular HSU patterns is poorly understood.
View Article and Find Full Text PDFDublin appears to have performed very well as compared to various scenarios for COVID-19 mortality amongst homeless and drug using populations. The experience, if borne out by further research, provides important lessons for policy discussions on the pandemic, as well as broader lessons about pragmatic responses to these key client groups irrespective of COVID-19. The overarching lesson seems that when government policy is well coordinated and underpinned by a science-driven and fundamentally pragmatic approach, morbidity and mortality can be reduced.
View Article and Find Full Text PDFThe vascular organ of the lamina terminalis, subfornical organ (SFO), and area postrema comprise the sensory circumventricular organs (CVO) which are central structures that lie outside the blood brain barrier and are thought to provide an interface between peripherally circulating signals and the brain through their projections to central autonomic structures. The SFO expresses mRNA for the G protein-coupled apelin receptor (APJ, gene name aplnr) and exogenous microinjection of the neuropeptide apelin (apln) to the SFO elicits a depressor effect. Here we investigated the expression and cellular distribution of aplnr, apln and the recently described ligand apela (apela) in the CVOs and investigated whether differences in the levels of expression of apelinergic gene transcripts in these regions might underlie the chronic elevated blood pressure seen in hypertension.
View Article and Find Full Text PDFPrion-like behaviour is an abrupt process, an "all-or-nothing" transition between a monomeric species and an "infinite" fibrillated form. Once a nucleation point is formed, the process is unstoppable as fibrils self-propagate by recruiting and converting all monomers into the amyloid fold. After the "mad cow" episode, prion diseases have made the headlines, but more and more prion-like behaviours have emerged in neurodegenerative diseases, where formation of fibrils and large conglomerates of proteins deeply disrupt the cell homeostasis.
View Article and Find Full Text PDFWe describe and evaluate the North Dublin City General Practitioner Training Programme (NDCGP), which was designed to educate doctors to work with the underserved. People who are marginalised have poorer health and less access to healthcare than the general population. Furthermore, these groups have significantly lower numbers of GPs per capita of population.
View Article and Find Full Text PDFThere is a growing need for operational oceanographic predictions in both the Arctic and Antarctic polar regions. In the former, this is driven by a declining ice cover accompanied by an increase in maritime traffic and exploitation of marine resources. Oceanographic predictions in the Antarctic are also important, both to support Antarctic operations and also to help elucidate processes governing sea ice and ice shelf stability.
View Article and Find Full Text PDFBackground: Homeless people have poor health and mortality indices. Despite this they make poor usage of health services. This study sought to understand why they use health services differently from the domiciled population.
View Article and Find Full Text PDFBackground: Hepatitis C virus (HCV) is one of the main causes of chronic liver disease worldwide. Prevalence of HCV in homeless populations ranges from 3.9 to 36.
View Article and Find Full Text PDFBackground: Higher-order self-assembly of proteins, or "prion-like" polymerisation, is now emerging as a simple and robust mechanism for signal amplification, in particular within the innate immune system, where the recognition of pathogens or danger-associated molecular patterns needs to trigger a strong, binary response within cells. MyD88, an important adaptor protein downstream of TLRs, is one of the most recent candidates for involvement in signalling by higher order self-assembly. In this new light, we set out to re-interpret the role of polymerisation in MyD88-related diseases and study the impact of disease-associated point mutations L93P, R196C, and L252P/L265P at the molecular level.
View Article and Find Full Text PDFBackground: Influenza during pregnancy is a potentially life threatening illness. There are limited data on influenza vaccination uptake and determinants of uptake in Irish obstetric populations.
Aim: To determine the uptake of influenza vaccination during pregnancy; determinants of vaccination uptake; knowledge, attitudes, and concerns of postnatal women; and knowledge and attitudes of healthcare professionals (HCPs) surrounding vaccination.
Background: Vaccination against influenza and pertussis in pregnancy can reduce the significant morbidity and mortality associated with these infections. Despite this, there is poor uptake of both vaccines in pregnancy.
Aim: To explore women's perception of vaccination in pregnancy and thereby determine the reasons behind such low vaccination rates.
The murine cytomegalovirus protein M45 protects infected mouse cells from necroptotic death and, when heterologously expressed, can protect human cells from necroptosis induced by tumour necrosis factor receptor (TNFR) activation. Here, we show that the N-terminal 90 residues of the M45 protein, which contain a RIP homotypic interaction motif (RHIM), are sufficient to confer protection against TNFR-induced necroptosis. This N-terminal region of M45 drives rapid self-assembly into homo-oligomeric amyloid fibrils and interacts with the RHIMs of the human kinases RIPK1 and RIPK3, and the Z-DNA binding protein 1 (ZBP1), to form heteromeric amyloid fibrils Mutation of the tetrad residues in the M45 RHIM attenuates homo- and hetero-amyloid assembly by M45, suggesting that the amyloidogenic nature of the M45 RHIM underlies its biological activity.
View Article and Find Full Text PDFDysfunction of the apelinergic system, comprised of the neuropeptide apelin mediating its effects via the G protein-coupled apelin receptor (APJ), may underlie the onset of cardiovascular disease such as hypertension. Apelin expression is increased in the rostral ventrolateral medulla (RVLM) in spontaneously hypertensive rats (SHRs) compared to Wistar-Kyoto (WKY) normotensive rats, however, evidence that the apelinergic system chronically influences mean arterial blood pressure (MABP) under pathophysiological conditions remains to be established. In this study we investigated, in conscious unrestrained rats, whether APJ contributes to MABP and sympathetic vasomotor tone in the progression of two models of hypertension - SHR and -NAME-treated rats - and whether APJ contributes to the development of hypertension in pre-hypertensive SHR.
View Article and Find Full Text PDFBackground: Homeless people experience substantially higher rates of illness and significant barriers to accessing health services. The mobile health clinic (MHC), staffed by trainee general practitioners, targets and provides homeless people in Dublin with free and easy access to primary healthcare services.
Aims: To explore and determine the specific health reasons for attending the mobile health unit and to investigate whether the MHC improves access to primary healthcare for homeless people.
Caveolae have been linked to the regulation of signaling pathways in eukaryotic cells through direct interactions with caveolins. Here, we describe a cell-free system based on () extracts for the biogenesis of caveolae and show its use for single-molecule interaction studies. Insertion of expressed caveolin-1 (CAV1) into membranes was analogous to that of caveolin in native membranes.
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