A successful centre for translational paediatric surgical research.

The National Children's Research Centre (NCRC), the single largest paediatric research centre in Ireland, has been in existence for over 50 years and is located on the grounds of the largest children's hospital in Ireland; Children's Health Ireland at Crumlin. Professor Puri was appointed as the Director of the Research in 1989 and became President of the NCRC in 2009, a position he held until 2016. Professor Puri is one of the most cited paediatric surgical researchers in the world.

Translational research in Hirschprung's disease at the National Children's Research Centre in Dublin.

Hirschsprung's disease (HD) is a congenital condition characterised by aganglionosis in the distal bowel. Over the years, at the National Children's Research Centre (NCRC), HD has been one of the most prominent and successful research areas for Prof. Prem Puri's research team.

SARS-CoV-2 antibody responses post-vaccination in UK healthcare workers with pre-existing medical conditions: a cohort study.

Objectives: To examine antibody responses after the second vaccination in healthcare workers (HCWs) with underlying health conditions.

Design: Cohort study.

Setting: Oxford University Hospitals in the United Kingdom.

An Observational Cohort Study on the Incidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and B.1.1.7 Variant Infection in Healthcare Workers by Antibody and Vaccination Status.

Background: Natural and vaccine-induced immunity will play a key role in controlling the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. SARS-CoV-2 variants have the potential to evade natural and vaccine-induced immunity.

Methods: In a longitudinal cohort study of healthcare workers (HCWs) in Oxfordshire, United Kingdom, we investigated the protection from symptomatic and asymptomatic polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection conferred by vaccination (Pfizer-BioNTech BNT162b2, Oxford-AstraZeneca ChAdOx1 nCOV-19) and prior infection (determined using anti-spike antibody status), using Poisson regression adjusted for age, sex, temporal changes in incidence and role.

Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers.

Background: The relationship between the presence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the risk of subsequent reinfection remains unclear.

Methods: We investigated the incidence of SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) in seropositive and seronegative health care workers attending testing of asymptomatic and symptomatic staff at Oxford University Hospitals in the United Kingdom. Baseline antibody status was determined by anti-spike (primary analysis) and anti-nucleocapsid IgG assays, and staff members were followed for up to 31 weeks.

Differential occupational risks to healthcare workers from SARS-CoV-2 observed during a prospective observational study.

We conducted voluntary Covid-19 testing programmes for symptomatic and asymptomatic staff at a UK teaching hospital using naso-/oro-pharyngeal PCR testing and immunoassays for IgG antibodies. 1128/10,034 (11.2%) staff had evidence of Covid-19 at some time.

Altered anoctamin-1 and tyrosine phosphorylation in congenital ureteropelvic junction obstruction.

Purpose: Ureteropelvic junction (UPJ) obstruction is the most common cause of congenital hydronephrosis in children. The pathophysiology of UPJ obstruction and the exact mechanism of pelviureteral peristalsis are poorly understood. Anoctamin-1 (ANO1), a Ca-activated chloride channel, has been shown to play a key role in muscle wall contractions in the gastrointestinal tract.

Increased protease activated receptors in the colon of patients with Hirschsprung's disease.

Purpose: The pathophysiology of Hirschsprung's associated enterocolitis (HAEC) is not understood. Abnormal intestinal motility and altered intestinal epithelial barrier function have been suggested to play a key role in the causation of HAEC. Protease-activated receptors (PARs) 1 and 2, have been implicated in inflammatory reactions, intestinal permeability and modulation of motility in the gut.

Tuft Cells: A New Player in Hirschsprung's Disease.

Introduction:  "Tuft" cells, also known as brush or caveolated cells, are characteristically fusiform shaped, with a distinct apical "tuft" of microvilli extending into the lumen. Double cortin-like kinase 1 (DCLK1) is a microtubule kinase and is a specific marker of intestinal tuft cells. DCLK1-positive tuft cells have been shown to play a key role in gastrointestinal chemosensation, inflammation, and neurotransmission.

Decreased expression of TRAAK channels in Hirschsprung's disease: a possible cause of postoperative dysmotility.

Aim Of The Study: Potassium (K) channels with a two-pore domain (K2P) are a large family of hyperpolarising ion channels which play a key role in cell excitability. This family comprises three members: TREK-1, TREK-2 and TRAAK. TRAAK channels have previously been reported to be expressed in murine enteric ganglia.

Altered ryanodine receptor gene expression in Hirschsprung's disease.

Aim Of The Study: Ryanodine receptors are the largest of all ion channels, named after their exogenous ligand, ryanodine. The ryanodine receptor calcium release channel is central to cytoplasmic Ca signalling in skeletal muscle, the heart, and many other tissues, playing a vital role in muscular contraction. Three ryanodine receptors exist, Ryr1, Ryr2 and Ryr3.

Altered expression of caveolin-1 in the colon of patients with Hirschsprung's disease.

Background/purpose: The pathogenesis of Hirschsprung's disease-associated enterocolitis (HAEC) is unclear. Caveolin-1 (Cav-1) regulates the functions of different nitric oxide synthase (NOS) isoforms, which play critical roles in inflammation and intestinal epithelial barrier function. We designed this study to investigate the hypothesis that Cav-1 expression is altered in the bowel of patients with Hirschsprung's disease (HSCR).

The Extent of the Transition Zone in Hirschsprung Disease.

Background: Retained transition zone is a leading cause of obstructive symptoms after pull-through operation in Hirschsprung's disease.

Objective: We aimed to evaluate the extent of the histological transition zone in patients with Hirschsprung's disease.

Design: We performed an observational study.

Altered expression of inflammasomes in Hirschsprung's disease.

Aim Of The Study: The pathogenesis of Hirschsprung's disease-associated enterocolitis (HAEC) is poorly understood. Inflammasomes are a large family of multiprotein complexes that act to mediate host immune responses to microbial infection and have a regulatory or conditioning influence on the composition of the microbiota. Inflammasomes and the apoptosis-associated speck-like protein (ASC) lead to caspase-1 activation.

Altered expression of KCNG3 and KCNG4 in Hirschsprung's disease.

Purpose: Voltage-gated potassium ion channels have long been implicated in gastrointestinal motility. Recent studies have highlighted the role of voltage-gated channel subfamily G member 3 (KCNG3) and 4 (KCNG4) genes in the electrical functioning of interstitial cells of Cajal and PDGFRα cells of the mouse colon. We designed this study to investigate KCNG3 and KCNG4 expression in the normal human colon and in Hirschsprung's disease (HSCR).

Abnormal Scn1b and Fxyd1 gene expression in the pulled-through ganglionic colon may influence functional outcome in patients with Hirschsprung's disease.

Purpose: Smooth muscle cells are electrically coupled to ICC and PDGFRα cells, to regulate smooth muscle contraction. Recent studies have reported that the voltage-gated sodium channel type 1β (Scn1b), and the chloride channel subunit, Fxyd1, are highly expressed by both ICC and PDGFRα cells in the mouse colon. We designed this study to investigate the expression of the Scn1b and Fxyd1 genes in the normal human colon and in HSCR.

Consanguinity and its relevance for the incidence of megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS): systematic review.

Background/purpose: Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare congenital and generally fatal cause of functional intestinal obstruction in the newborn. The cause of this syndrome is unknown. Familial occurrence and reports of consanguinity in MMIHS implies that genetic factors may have an important role in the pathogenesis of this syndrome.

Reduced expression of the NLRP6 inflammasome in the colon of patients with Hirschsprung's disease.

Purpose: Hirschsprung's associated enterocolitis (HAEC) is the most common cause of morbidity and mortality in Hirschsprung's Disease (HSCR). The pathogenesis of HAEC remains unsatisfactorily understood. Mounting evidence of an altered microbiome in patients with HSCR adds a new angle to the pathogenesis of HAEC.

Increased population of immature enteric glial cells in the resected proximal ganglionic bowel of Hirschsprung's disease patients.

Background: Enteric glial cells are essential for normal gastrointestinal function. Abnormalities in glial structure, development, or function lead to disturbances in gastrointestinal physiology. Fatty acid-binding protein 7 (FABP7) is a marker of immature enteric glial cells, whereas S100 is expressed only by mature glial cells.

Platelet-derived growth factor receptor alpha-positive cells: a new cell type in the human ureteropelvic junction.

Background: Ureteropelvic junction (UPJ) obstruction is the most common cause of congenital hydronephrosis. Normal ureteral motility requires coordinated interaction between neurons, smooth muscle cells (SMCs), and interstitial Cajal-like cells (IC-LCs). Recently, a new type of interstitial cell, platelet-derived growth factor receptor α-positive (PDGFRα) cells, was discovered in the gastrointestinal tract and bladder.

Reduction of hydrogen sulfide synthesis enzymes cystathionine-β-synthase and cystathionine-γ-lyase in the colon of patients with Hirschsprungs disease.

Purpose: Hirschsprung associated enterocolitis (HAEC) is the most common cause of morbidity and mortality in Hirschsprung Disease (HSCR). The pathogenesis of HAEC is poorly understood. In recent years, there is increasing evidence that a compromised intestinal barrier function plays a major role in the pathogenesis of HAEC.

NOS-interacting protein (NOSIP) is increased in the colon of patients with Hirschsprungs's disease.

Purpose: Hirschsprung's associated enterocolitis (HAEC) is the most common cause of morbidity and mortality in Hirschsprung's disease (HSCR). Nitric oxide (NO) mediates intestinal homoeostasis and is inhibited by NOSIP, a modulator of NO production. We designed this study to investigate the expression of NOSIP in the colon of patients with HSCR.

Decreased expression of Kv7 channels in Hirchsprung's disease.

Purpose: Voltage-dependent K channels (Kv channels) participate in electrical rhythmicity and smooth muscle responses and are regulated by excitatory and inhibitory neurotransmitters. Kv channels also participate in the interstitial cell of Cajal (ICC) and smooth muscle cell (SMC) responses to neural inputs. The Kv family consists of 12 subfamilies, Kv1-Kv12, with five members of the Kv7 family identified to date: Kv7.

Expression of connexin 26 and connexin 43 is reduced in Hirschsprung's disease.

Background: Despite having an optimal pull-through operation, some children with Hirschsprung's disease (HSCR) continue to experience persistent bowel symptoms. Coordinated colonic electrical activity depends on intercellular communication between the enteric nerves, interstitial cells of Cajal (ICCs), smooth muscle cells, and fibroblast-like (platelet-derived growth factor receptor-alpha-positive) cells. Gap junctions are low-resistance channels composed of connexin (Cx) proteins which couple cells electrically and chemically.