Background: Restraining or slowing ageing hallmarks at the cellular level have been proposed as a route to increased organismal lifespan and healthspan. Consequently, there is great interest in anti-ageing drug discovery. However, this currently requires laborious and lengthy longevity analysis.
View Article and Find Full Text PDFBackground: Moya moya type vasculopathy (MMV) is a rare disorder in which there is narrowing of bilateral intracranial carotid arteries (Scott and Smith in New Engl J Med 360(12):1226-1237, 2009). MECP2 duplication syndrome (MDS) is a rare genetic disorder that is caused by genetic duplications on Xq28 chromosome (Expanding the clinical picture of the MECP2 duplication syndrome. (Lim et al.
View Article and Find Full Text PDFDenitrification is a major biological source and sink for the ozone-depleting greenhouse gas N2. Thus, the respiratory physiology of denitrifiers and the mechanisms determining their propensity for accumulation of N-oxides are of fundamental interest. Here, we report a pervasive positive correlation between cell density and N2O accumulation in Pseudomonas aeruginosa and P.
View Article and Find Full Text PDFAnn Otol Rhinol Laryngol
April 2023
Objective: Patient-provider communication is a major barrier to care, with some providers giving their personal phone number (PPN) to patients for increased accessibility. We investigated participant utilization of provider's PPN, its effect on participant satisfaction, provider's ability to predict abuse of this practice, and evolving provider perceptions.
Study Design: Prospective, randomized study.
Senescence occurs in response to a number of damaging stimuli to limit oncogenic transformation and cancer development. As no single, universal senescence marker has been discovered, the confident classification of senescence induction requires the parallel assessment of a series of hallmarks. Therefore, there is a growing need for "first-pass" tools of senescence identification to streamline experimental workflows and complement conventional markers.
View Article and Find Full Text PDFBackground: Postnatal steroids (PNS) have been used to prevent bronchopulmonary dysplasia (BPD) in preterm infants but have potential adverse effects on neurodevelopment. These effects might be modulated by their risk of BPD. We aimed to compare patients' neurodevelopment with PNS treatment according to their risk of BPD in a European cohort.
View Article and Find Full Text PDFAims: The aim of this study is to assess the impact of a pilot enhanced recovery after surgery (ERAS) programme on length of stay (LOS) and post-discharge resource usage via service evaluation and cost analysis.
Methods: Between May and December 2019, 100 patients requiring hip or knee arthroplasty were enrolled with the intention that each would have a preadmission discharge plan, a preoperative education class with nominated helper, a day of surgery admission and mobilization, a day one discharge, and access to a 24/7 dedicated helpline. Each was matched with a patient under the pre-existing pathway from the previous year.
Aims: Now that we are in the deceleration phase of the COVID-19 pandemic, the focus has shifted to how to safely reinstate elective operating. Regional and speciality specific data is important to guide this decision-making process. This study aimed to review 30-day mortality for all patients undergoing orthopaedic surgery during the peak of the pandemic within our region.
View Article and Find Full Text PDFMech Ageing Dev
September 2020
The recent advent of 'organs in a dish' has revolutionised the research landscape. These 3D culture systems have paved the way for translational, post genomics research by enabling scientists to model diseases in the laboratory, grow patient-derived organoids, and unite this technology with other cutting-edge methodologies such as drug discovery. Fields such as dermatology and neuroscience have revolutionised the development of robust 3D models, which faithfully recapitulate native physiology in vivo to provide important functional and mechanistic insights.
View Article and Find Full Text PDFIntroduction: Postnatal corticosteroids (PNC) are effective for reducing bronchopulmonary dysplasia (BPD) in very preterm neonates but are associated with adverse effects including an increased risk of cerebral palsy. PNC use in Europe is heterogeneous across regions. This study aimed to assess whether European neonatal intensive care units (NICUs) with a low use of PNC or an explicit policy to reduce PNC use had higher risks of mortality or BPD.
View Article and Find Full Text PDFAims: To monitor the performance of services for developmental dysplasia of the hip (DDH) in Northern Ireland and identify potential improvements to enhance quality of service and plan for the future.
Methods: This was a prospective observational study, involving all infants treated for DDH between 2011 and 2017. Children underwent clinical assessment and radiological investigation as per the regional surveillance policy.
Introduction: The management of paediatric femoral fractures continues to spark debate in published literature, with poor quality evidence guiding current guidelines on the optimum treatment in children. Many centres report excellent results for both elastic intramedullary nailing and plate fixation of diaphyseal femoral fractures. This study aimed to investigate the outcomes of femoral fractures treated with elastic nail fixation versus those treated with plate fixation in a tertiary children's trauma unit, and discuss the advantages and disadvantages of each technique.
View Article and Find Full Text PDFBackground: Increasing numbers of Total Knee Arthroplasty (TKA) operations are carried out worldwide each year. This brings with it an ever-increasing revision burden and it is therefore important to appreciate both the functional outcome and survivorship of established arthroplasties when considering new designs. We aim to evaluate the long-term survivorship of a fully cemented mobile bearing Total Knee Arthroplasty.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2018
When oxygen becomes limiting, denitrifying bacteria must prepare for anaerobic respiration by synthesizing the reductases NAR (NO → NO), NIR (NO → NO), NOR (2NO → NO), and NOS (NO → N), either or sequentially, to avoid entrapment in anoxia without energy. Minimizing the metabolic burden of this precaution is a plausible fitness trait, and we show that the model denitrifier achieves this by synthesizing NOS in all cells, while only a minority synthesize NIR. Phenotypic diversification with regards to NIR is ascribed to stochastic initiation of gene transcription, which becomes autocatalytic via NO production.
View Article and Find Full Text PDFBackground: Adverse effects on reproductive function are a key concern in young women treated with chemotherapy for advanced Hodgkin's lymphoma. We aimed to identify risk factors for the extent of ovarian damage in women with Hodgkin's lymphoma treated with different chemotherapy regimens to inform accurate advice on options for fertility preservation.
Methods: We recruited female participants from the randomised phase 3 RATHL trial, aged 18-45 years, based on availability of participants at recruiting sites in the UK.
Introduction: The Royal Victoria Hospital in Belfast is the largest volume hospital in the UK Hip Fracture Database. Management of displaced intra-capsular hip fractures is evolving in light of NICE and BOA guidelines, with more patients receiving total hip replacement (THR) over hemi-arthroplasty. With current rationing within the NHS, it is vital that principles of the 'Getting It Right First time' (GIRFT) report are implemented and the correct treatment choice made.
View Article and Find Full Text PDFARCTIC was a multicenter, randomized-controlled, open, phase IIB non-inferiority trial in previously untreated chronic lymphocytic leukemia (CLL). Conventional frontline therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). The trial hypothesized that including mitoxantrone with low-dose rituximab (FCM-miniR) would be non-inferior to FCR.
View Article and Find Full Text PDFObjective: To investigate changes in maternity and neonatal unit policies towards extremely preterm infants (EPTIs) between 2003 and 2012, and concurrent trends in their mortality and morbidity in ten European regions.
Design: Population-based cohort studies in 2003 (MOSAIC study) and 2011/2012 (EPICE study) and questionnaires from hospitals.
Setting: 70 hospitals in ten European regions.
Background: Spontaneous closure of patent ductus arteriosus (PDA) occurs frequently in very preterm infants and despite the lack of evidence for treatment benefits, treatment for PDA is common in neonatal medicine.
Objectives: The aim of this work was to study regional variations in PDA treatment in very preterm infants (≤31 weeks of gestation), its relation to differences in perinatal characteristics, and associations with bronchopulmonary dysplasia (BPD) and survival without major neonatal morbidity.
Methods: This was a population-based cohort study in 19 regions in 11 European countries conducted during 2011 and 2012.
Background: Postnatal corticosteroids (PNC) were widely used to treat and prevent bronchopulmonary dysplasia in preterm infants until studies showed increased risk of cerebral palsy and neurodevelopmental impairment. We aimed to describe PNC use in Europe and evaluate the determinants of their use, including neonatal characteristics and adherence to evidence-based practices in neonatal intensive care units (NICUs).
Methods: 3917/4096 (95,6%) infants born between 24 and 29 weeks gestational age in 19 regions of 11 European countries of the EPICE cohort we included.
With immunochemotherapy, remission duration and survival in patients with chronic lymphocytic leukaemia is dependent on the level of minimal residual disease (MRD) after treatment. This phase II trial assessed alemtuzumab consolidation post-chemotherapy in patients who responded with persistent low levels of detectable disease. Blood was screened for MRD using multi-parameter flow cytometry, 6-24 months post-chemotherapy.
View Article and Find Full Text PDFUp to 30% of adults with acute myeloid leukemia fail to achieve a complete remission after induction chemotherapy - termed primary refractory acute myeloid leukemia. There is no universally agreed definition of primary refractory disease, nor have the optimal treatment modalities been defined. We studied 8907 patients with newly diagnosed acute myeloid leukemia, and examined outcomes in patients with refractory disease defined using differing criteria which have previously been proposed.
View Article and Find Full Text PDFThe study was designed to compare clofarabine plus daunorubicin vs daunorubicin/ara-C in older patients with acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS). Eight hundred and six untreated patients in the UK NCRI AML16 trial with AML/high-risk MDS (median age, 67 years; range 56-84) and normal serum creatinine were randomised to two courses of induction chemotherapy with either daunorubicin/ara-C (DA) or daunorubicin/clofarabine (DClo). Patients were also included in additional randomisations; ± one dose of gemtuzumab ozogamicin in course 1; 2v3 courses and ± azacitidine maintenance.
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