Background: Alcohol use in adolescence may increase susceptibility to substance use disorders (SUDs) in adulthood. This study determined if voluntary ethanol (EtOH) consumption during adolescence, combined with social isolation, alters the trajectory of EtOH and nicotine intake during adulthood, as well as activating brain neuroinflammation.
Methods: Adolescent male isolate- and group-housed rats were given 0.
The emergence of antimicrobial resistance has created an urgent need for alternative treatments against bacterial pathogens. Here, we investigated kinase inhibitors as potential host-directed therapies (HDTs) against intracellular bacteria, specifically Salmonella Typhimurium (Stm) and Mycobacterium tuberculosis (Mtb). We screened 827 ATP-competitive kinase inhibitors with known target profiles from two Published Kinase Inhibitor Sets (PKIS1 and PKIS2) using intracellular infection models for Stm and Mtb, based on human cell lines and primary macrophages.
View Article and Find Full Text PDFObjective: The study objective was to determine whether adequately delivered bilateral remote ischemic preconditioning is cardioprotective in young children undergoing surgery for 2 common congenital heart defects with or without cyanosis.
Methods: We performed a prospective, double-blind, randomized controlled trial at 2 centers in the United Kingdom. Children aged 3 to 36 months undergoing tetralogy of Fallot repair or ventricular septal defect closure were randomized 1:1 to receive bilateral preconditioning or sham intervention.
The increasing prevalence of antimicrobial-resistant strains, especially methicillin-resistant (MRSA), poses a threat to successful antibiotic treatment. Unsuccessful attempts to develop a vaccine and rising resistance to last-resort antibiotics urge the need for alternative treatments. Host-directed therapy (HDT) targeting critical intracellular stages of emerges as a promising alternative, potentially acting synergistically with antibiotics and reducing the risk of drug resistance.
View Article and Find Full Text PDFBackground: Globally, the tuberculosis (TB) treatment success rate is approximately 85%, with treatment failure, relapse and death occurring in a significant proportion of pulmonary TB patients. Treatment success is lower among people with diabetes mellitus (DM). Predicting treatment outcome early after diagnosis, especially in TB-DM patients, would allow early treatment adaptation for individuals and may improve global TB control.
View Article and Find Full Text PDFBackground: An intra-cardiac abscess is a serious complication of both native (NV-IE) and prosthetic valve infective endocarditis (PV-IE). Despite being an accepted indication for surgery, controversies remain regarding the optimal timing and type of operation. We aimed to report the outcomes of patients managed for intra-cardiac abscesses over more than a decade.
View Article and Find Full Text PDFIntroduction And Background: Mortality between stages 1 and 2 single-ventricle palliation is significant. Home-monitoring programmes are suggested to reduce mortality. Outcomes and risk factors for adverse outcomes for European programmes have not been published.
View Article and Find Full Text PDFDiabetes mellites (DM) is correlated with increased susceptibility to and disease progression of tuberculosis (TB), and strongly impairs effective global TB control measures. To better control the TB-DM co-epidemic, unravelling the bidirectional interactivity between DM-associated molecular processes and immune responses to ( is urgently required. Since poly (ADP-ribose) polymerase (PARP) activation has been associated with DM and with infection in mouse models, we have investigated whether PARP inhibition by pharmacological compounds can interfere with host protection against in human macrophage subsets, the predominant target cell of .
View Article and Find Full Text PDFGlobal increases in the prevalence of antimicrobial resistance highlight the urgent need for novel strategies to combat infectious diseases. Recent studies suggest that host metabolic pathways play a key role in host control of intracellular bacterial pathogens. In this study we explored the potential of targeting host metabolic pathways for innovative host-directed therapy (HDT) against intracellular bacterial infections.
View Article and Find Full Text PDFAlcohol is one of the most widely used recreational substances worldwide, with drinking frequently initiated during adolescence. The developmental state of the adolescent brain makes it vulnerable to initiating alcohol use, often in high doses, and particularly susceptible to alcohol-induced brain changes. Microglia, the brain parenchymal macrophages, have been implicated in mediating some of these effects, though the role that these cells play in the progression from alcohol drinking to dependence remains unclear.
View Article and Find Full Text PDFEur J Cardiothorac Surg
February 2022
Objectives: Since percutaneous pulmonary valve implantation (PPVI) was introduced to prolong the lifetime of surgically placed right ventricular to pulmonary artery conduits, valve technology has evolved and the indications for PPVI expanded to native and larger right ventricular outflow tracts. We explore how indications, patient populations and outcomes compare to surgical pulmonary valve replacement (PVR).
Methods: This is a retrospective cohort study of PPVI and PVR procedures between 1998 and 2020 at a single UK centre.
Introduction: Myocardial protection against ischaemic-reperfusion injury is a key determinant of heart function and outcome following cardiac surgery in children. However, with current strategies, myocardial injury occurs routinely following aortic cross-clamping, as demonstrated by the ubiquitous rise in circulating troponin. Remote ischaemic preconditioning, the application of brief, non-lethal cycles of ischaemia and reperfusion to a distant organ or tissue, is a simple, low-risk and readily available technique which may improve myocardial protection.
View Article and Find Full Text PDFObjectives: Many adults with repaired tetralogy of Fallot will require a pulmonary valve replacement (PVR), but there is no consensus on the best timing. In this study, we aim to evaluate the impact of age at PVR on outcomes.
Methods: This is a national multicentre retrospective study including all patients >15 years of age with repaired tetralogy of Fallot who underwent their first PVR between 2000 and 2013.
Background: Surgery in grown-ups with congenital heart disease (GUCH) is characterized by complex anatomy, comorbidities, reoperations, and technical challenges. Although 30-day postoperative mortality is low, this measure might be insufficient to reflect adverse outcome monitoring. Our study aimed to establish whether prolonged intensive care unit (ICU) stay (≥7 days) and 6-month mortality were more clinically meaningful measures than 30-day mortality and to identify predictors of adverse outcome.
View Article and Find Full Text PDFBackground: Patients with tetralogy of Fallot are now surviving to adulthood with timely surgical intervention. However, many patients in low-income countries have no access to surgical intervention. This paper reports the surgical access and perioperative mortality in a sub-Saharan center that was mainly dependent on visiting teams.
View Article and Find Full Text PDFWorld J Pediatr Congenit Heart Surg
January 2021
Coronary artery aneurysms in children are usually associated with inflammatory disease such as Kawasaki disease or connective tissue disease. Congenital coronary aneurysm is a rare entity with few case reports published in the literature. We report an unusual case of congenital coronary aneurysm in an 11-year-old boy presented to our center with an ischemic cardiac event.
View Article and Find Full Text PDFObjective: Left atrio-ventricular valve (LAVV) regurgitation after repair of an atrio-ventricular septal defect (AVSD) may necessitate further surgery. However, redo-LAVV repair remains challenging. We sought to determine if more LAVV valves are preserved in the current era, and analyze early and longer-term results.
View Article and Find Full Text PDFThe adipocyte-derived hormone leptin is an important regulator of body weight and metabolism through activation of brain leptin receptors expressed in regions such as the hypothalamus. Beyond these well described and characterized activities of leptin in the hypothalamus, it is becoming increasingly clear that the central activities of leptin extend to the hippocampus. Indeed, leptin receptors are expressed in the hippocampus where these receptors are proposed to mediate various aspects of hippocampal synaptic plasticity that ultimately impact cognitive function.
View Article and Find Full Text PDFBackground: Inadvertent ligation of the left pulmonary artery during attempted surgical closure of a Patent Ductus Arteriosus has long been recognized as one of the less common complications of this procedure. Surgical reconstruction of the left pulmonary artery was then often attempted but was difficult or impossible in some of the patients with hypoplasia of the left pulmonary artery and the left lung.
Case Presentation: A 10-year-old girl presented with marked exercise intolerance and palpitations and was diagnosed to have large PDA.
Background: The optimal surgical procedure for treatment of fibromembranous subaortic stenosis has been a subject of debate. We report our experience with patients treated for membranous subaortic stenosis using membrane resection alone and membrane resection plus aggressive septal myectomy.
Methods: Patients followed in the pediatric cardiology clinic of a university hospital, who had undergone surgery for subaortic stenosis between 2002 and 2013 were reviewed.