Seasonal variation in the incidence of preterm births.

Objectives: To examine the influence of the season of conception, and the season of birth on the incidence of preterm birth (PTB) and neonatal outcomes.

Study Design: This is a single center, retrospective cohort study of singleton births that took place in The Coombe Hospital in Dublin, Ireland, between January 2013 and December 2022. A comprehensive database was analyzed to determine the incidence of PTB per season of conception and season of birth.

The MicroRNA miR-223 Constrains Colitis-associated Tumorigenesis by Limiting Myeloid Cell Infiltration and Chemokine Expression.

Aberrant intestinal inflammation plays a critical role in the development of colitis-associated colorectal cancer (CAC), yet the mechanisms controlling tumor development by the myeloid immune compartment are not fully understood. Although altered microRNA expression is observed in CAC, it is also unclear how myeloid-specific microRNAs impact the inflammatory process that underpins the continuum from ulcerative colitis to tumorigenesis. In this study, we report that miR-223 acts to limit myeloid-driven inflammation in the azoxymethane (AOM)-dextran sodium sulfate (DSS) model of CAC in mice.

CSF1-dependent macrophage support matrisome and epithelial stress-induced keratin remodeling in Eosinophilic esophagitis.

Atopic diseases such as Eosinophilic Esophagitis (EoE) often progress into fibrosis (FS-EoE), compromising organ function with limited targeted treatment options. Mechanistic understanding of FS-EoE progression is confounded by the lack of preclinical models and the heavy focus of research on eosinophils themselves. We found that macrophage accumulation precedes esophageal fibrosis in FS-EoE patients.

HIF-2α-dependent induction of miR-29a restrains T1 activity during T cell dependent colitis.

Metabolic imbalance leading to inflammatory hypoxia and stabilization of hypoxia-inducible transcription factors (HIFs) is a hallmark of inflammatory bowel diseases. We hypothesize that HIF could be stabilized in CD4 T cells during intestinal inflammation and alter the functional responses of T cells via regulation of microRNAs. Our assays reveal markedly increased T cell-intrinsic hypoxia and stabilization of HIF protein during experimental colitis.

Metabolic dysfunction mediated by HIF-1α contributes to epithelial differentiation defects in eosinophilic esophagitis.

Background: Investigating the contributory role that epithelial cell metabolism plays in allergic inflammation is a key factor to understanding what influences dysfunction and the pathogenesis of the allergic disease eosinophilic esophagitis (EoE). We previously highlighted that the absence of hypoxia signaling through hypoxia-inducible factor (HIF)-1α in EoE contributes to esophageal epithelial dysfunction. However, metabolic regulation by HIF-1α has not been explored in esophageal allergy.

Mesenchymal stromal cells dampen trained immunity in house dust mite-primed macrophages expressing human macrophage migration inhibitory factor polymorphism.

Background: Trained immunity results in long-term immunological memory, provoking a faster and greater immune response when innate immune cells encounter a secondary, often heterologous, stimulus. We have previously shown that house dust mite (HDM)-induced innate training is amplified in mice expressing the human macrophage migration inhibitory factor (MIF) CATT functional polymorphism.

Aim: This study investigated the ability of mesenchymal stromal cells (MSCs) to modulate MIF-driven trained immunity both in vitro and in vivo.

The human MIF polymorphism CATT enhances pro-inflammatory macrophage polarization in a clinically relevant model of allergic airway inflammation.

High level expression of the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) has been associated with severe asthma. The role of MIF and its functional promotor polymorphism in innate immune training is currently unknown. Using novel humanized CATT MIF mice, this study is the first to investigate the effect of MIF on bone marrow-derived macrophage (BMDM) memory after house dust mite (HDM) challenge.

Homelessness in pregnancy.

Objectives: To evaluate the association, if any, of homelessness or refuge accommodation on delivery and short term perinatal outcomes in an Irish tertiary maternity hospital.

Methods: A retrospective cohort study of 133 singleton pregnancies in women reporting to be homeless or living in refuge at their booking antenatal appointment between 2013 and 2022. Analysis compared sociodemographic characteristics and perinatal outcomes in this cohort to a reference population of 76,858 women with stable living arrangements.

Hypoxia-inducible microRNA-155 negatively regulates epithelial barrier in eosinophilic esophagitis by suppressing tight junction claudin-7.

MicroRNA (miRNA)-mediated mRNA regulation directs many homeostatic and pathological processes, but how miRNAs coordinate aberrant esophageal inflammation during eosinophilic esophagitis (EoE) is poorly understood. Here, we report a deregulatory axis where microRNA-155 (miR-155) regulates epithelial barrier dysfunction by selectively constraining tight junction CLDN7 (claudin-7). MiR-155 is elevated in the esophageal epithelium of biopsies from patients with active EoE and in cell culture models.

MicroRNA dysregulation and therapeutic opportunities in esophageal diseases.

MicroRNAs (miRNAs) are a class of small endogenous RNA molecules between 18 and 25 nucleotides long. The primary function of miRNAs is in the posttranscriptional regulation of mRNA targets through RNA interference culminating in mRNA degradation or translational repression. MiRNAs are fundamental in physiological and pathological processes such as cell proliferation, differentiation, apoptosis, and inflammation.

The duration of labor in spontaneous preterm deliveries: A retrospective observational study in a tertiary Irish maternity hospital.

Background: Preterm deliveries account for 10% of all births, and are the most important cause of neonatal mortality globally. Despite their frequency, there is a paucity of information known about usual patterns of preterm labor, as previous studies which critically defined the normal progression of labor excluded preterm gestations.

Objective: To compare the durations of the first, second and third stages of spontaneous preterm labor in nulliparous and multiparous women at varying preterm gestations.

Demographic changes in primiparae of Irish ethnicity between 2000 and 2020.

Background: Trends in maternal demographic changes linked to lifestyle and socio-economic conditions reflect greatly on maternal, perinatal and infant mortality rates. Hospital data reflect a heterogenous population where specific demographic changes may not be obvious.

Objectives: To report yearly demographic changes in Irish primiparae from 2000 to 2020, specifically looking at age, BMI, smoking and marital status of patients attending the Coombe Women and Infant's University Hospital (CWIUH).

Non-diabetic fetal macrosomia: outcomes of elective delivery versus expectant management.

Background: Macrosomia in the absence of diabetes can be associated with increased neonatal and maternal morbidity. Management is usually undertaken on a case-by-case basis.

Aims: In order to inform local practice, this study aimed to evaluate the outcomes of the management of non-diabetic macrosomia in an Irish tertiary center.

Recruitment strategies for a pragmatic cluster randomized oral health trial in pediatric primary care settings.

Objectives: To describe multilevel recruitment strategies for an ongoing clinical trial in pediatric primary care settings, and assess adoption and reach of these strategies via the RE-AIM framework.

Methods: This study is part of a larger pragmatic cluster randomized clinical trial focused on the effectiveness of interventions on the practice, provider, and caregiver levels on dental utilization for Medicaid-enrolled 3-6 year old children. Pediatric practices were recruited according to the proportion of Medicaid-eligible children, geographic region, and County.

The impact of the Covid-19 pandemic on maternity services: A review of maternal and neonatal outcomes before, during and after the pandemic.

Objective: To explore any apparent trends in maternal or neonatal outcomes during the Covid-19 pandemic by comparing the maternity outcomes before, during and after the pandemic.

Study Design: A retrospective review was performed of maternity statistics recorded on the hospital database of a large tertiary referral centre in Dublin with over 8000 deliveries per annum from 1st January to 31st July 2020. This time period represented the months prior to, during the peak and following the pandemic in Ireland.

Caries disparities among Medicaid-enrolled young children from pediatric primary care settings.

Objectives: The objectives of this study are to determine the overall and racial differences in the extent of caries experience and to examine the association between child and parent/caregiver characteristics and caries among 3-6-year-old Medicaid-enrolled children.

Methods: This study reports baseline cross-sectional data from a larger pragmatic clinical trial in pediatric primary care practices. Child-level clinical dental exams included decayed and filled teeth (dft) using ICDAS criteria and parent/caregiver questionnaire collected information on socio-demographics, child oral health behaviors, oral health related quality of life (OHQoL), and food environment.

Muc5ac Expression Protects the Colonic Barrier in Experimental Colitis.

Background: The mucus gel layer (MGL) lining the colon is integral to exclusion of bacteria and maintaining intestinal homeostasis in health and disease. Some MGL defects allowing bacteria to directly contact the colonic surface are commonly observed in ulcerative colitis (UC). The major macromolecular component of the colonic MGL is the secreted gel-forming mucin MUC2, whose expression is essential for homeostasis in health.

Epithelial HIF-1α/claudin-1 axis regulates barrier dysfunction in eosinophilic esophagitis.

Epithelial barrier dysfunction is a significant factor in many allergic diseases, including eosinophilic esophagitis (EoE). Infiltrating leukocytes and tissue adaptations increase metabolic demands and decrease oxygen availability at barrier surfaces. Understanding of how these processes impact barrier is limited, particularly in allergy.

Cellular Plasticity of Defa4-Expressing Paneth Cells in Response to Notch Activation and Intestinal Injury.

Background & Aims: Loss of leucine-rich repeat-containing G-protein-coupled receptor 5-positive crypt base columnar cells provides permissive conditions for different facultative stem cell populations to dedifferentiate and repopulate the stem cell compartment. In this study, we used a defensin α4-Cre recombinase (Defa4Cre) line to define the potential of Paneth cells to dedifferentiate and contribute to intestinal stem cell (ISC) maintenance during normal homeostasis and after intestinal injury.

Methods: Small intestine and enteroids from Defa4;Rosa26 tandem dimer Tomato (tdTomato), a red fluoresent protein, (or Rosa26 Enhanced Yellow Fluorescent Protein (EYFP)) reporter, Notch gain-of-function (Defa4;Rosa26 Notch Intracellular Domain (NICD)-ires-nuclear Green Fluorescent Protein (nGFP) and Defa4;Rosa26 Enhanced Green Fluorescent Protein (EGFP);TetO), A Disintegrin and Metalloproteinase domain-containing protein 10 (ADAM10) loss-of-function (Defa4;ADAM10), and Adenomatous polyposis coli (APC) inactivation (Defa4;APC) mice were analyzed.

Neutrophil-derived microRNAs put the (DNA) breaks on intestinal mucosal healing.

A predominant feature of intestinal inflammation is the accumulation of neutrophils, which dictates a fine balance between epithelial repair or progression to chronic inflammation. While the processes of mucosal healing are well studied, how neutrophils advance an inflammatory insult towards epithelial neoplasia is less understood. In this issue of the JCI, Butin-Israeli et al.

Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome.

MicroRNA (miRNA)-mediated RNA interference regulates many immune processes, but how miRNA circuits orchestrate aberrant intestinal inflammation during inflammatory bowel disease (IBD) is poorly defined. Here, we report that miR-223 limits intestinal inflammation by constraining the nlrp3 inflammasome. miR-223 was increased in intestinal biopsies from patients with active IBD and in preclinical models of intestinal inflammation.