Eosinophilic esophagitis drives tissue fibroblast regenerative programs toward pathologic dysfunction.

Background: Pathologic tissue remodeling with scarring and tissue rigidity has been demonstrated in inflammatory, autoimmune, and allergic diseases. Eosinophilic esophagitis (EoE) is an allergic disease that is diagnosed and managed by repeated biopsy procurement, allowing an understanding of tissue fibroblast dysfunction. While EoE-associated tissue remodeling causes clinical dysphagia, food impactions, esophageal rigidity, and strictures, molecular mechanisms driving these complications remain under investigation.

The TNFSF12/TWEAK Modulates Colonic Inflammatory Fibroblast Differentiation and Promotes Fibroblast-Monocyte Interactions.

Fibroblasts acquire a proinflammatory phenotype in inflammatory bowel disease, but the factors driving this process and how fibroblasts contribute to mucosal immune responses are incompletely understood. TNF superfamily member 12 (TNFSF12, or TNF-like weak inducer of apoptosis [TWEAK]) has gained interest as a mediator of chronic inflammation. In this study, we explore its role as a driver of inflammatory responses in fibroblasts and its contribution to fibroblast-monocyte interaction using human primary colonic fibroblasts, THP-1 and primary monocytes.

Pelvic + Anatomy: A new interactive pelvic anatomy model. Prospective randomized control trial with first-year midwife residents.

Detailed knowledge of female pelvic floor anatomy is essential for midwifery and other professionals in obstetrics. Physical models have shown great potential for teaching anatomy and enhancing surgical skills. In this article, we introduce an innovative physical anatomy model called "Pelvic+" to teach anatomical relationships in the female pelvis.

Novel fibroblast phenotypes in homeostasis and chronic inflammation: From functions to potential regulators.

Fibroblasts are essential components of the stroma, sustaining a variety of tissues and being key to the process of tissue repair after injury. Their role in tissue repair has been attributed to their ability to acquire a contractile, extracellular matrix-producing phenotype known as myofibroblasts. This property is primarily dependent on their response to the pleiotropic cytokine transforming growth factor-β1.

Lymphotoxin beta receptor signaling directly controls airway smooth muscle deregulation and asthmatic lung dysfunction.

Background: Dysregulation of airway smooth muscle cells (ASM) is central to the severity of asthma. Which molecules dominantly control ASM in asthma is unclear. High levels of the cytokine LIGHT (aka TNFSF14) have been linked to asthma severity and lower baseline predicted FEV percentage, implying that signals through its receptors might directly control ASM dysfunction.

A Deficiency in the Cytokine TNFSF14/LIGHT Limits Inflammation and Remodeling in Murine Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic type 2 allergic disease, with esophageal tissue remodeling as the mechanism behind clinical dysphagia and strictures. IL-13 is thought to be a central driver of disease, but other inflammatory factors, such as IFNs and TNF superfamily members, have been hypothesized to play a role in disease pathogenesis. We recently found that the cytokine TNFSF14/LIGHT is upregulated in the esophagus of patients with EoE and that LIGHT promotes inflammatory activity in esophageal fibroblasts.

A Deficiency in the Cytokine TNFSF14/LIGHT Limits Inflammation and Remodeling in Murine Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic type 2 allergic disease, with esophageal tissue remodeling as the mechanism behind clinical dysphagia and strictures. IL-13 is thought to be a central driver of disease, but other inflammatory factors, such as IFNs and TNF superfamily members, have been hypothesized to play a role in disease pathogenesis. We recently found that the cytokine TNFSF14/LIGHT is upregulated in the esophagus of patients with EoE and that LIGHT promotes inflammatory activity in esophageal fibroblasts.

Type 2 Immunity and Age Modify Gene Expression of Coronavirus-induced Disease 2019 Receptors in Eosinophilic Gastrointestinal Disorders.

Infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can lead to coronavirus-induced disease 2019 (COVID-19). The gastrointestinal (GI) tract is now an appreciated portal of infection. SARS-CoV-2 enters host cells via angiotensin-converting enzyme-2 (ACE2) and the serine protease TMPRSS2.

Evaluation of midwifery pelvic floor education and Training across the UK and Spain.

Objectives: The aim of this study was to evaluate current education and training of student and registered midwives across the UK and Spain; analysing both pelvic floor teaching and practical experience.

Study Design: A cross-sectional survey was carried out by 711 student and 384 registered midwives across different universities and regions in the UK and Spain.

Results: The vast majority (91.

Animal Models of Contact Dermatitis: 2,4-Dinitrofluorobenzene-Induced Contact Hypersensitivity.

Allergic contact dermatitis (ACD) is a common skin disease with high prevalence in work environments. Human allergic contact dermatitis is triggered by the exposure to haptens that leads to an initial phase known as sensitization. During this phase, hapten-protein complexes presented by antigen-presenting cells activate a T-cell-mediated response, leading to the generation of memory cells against the hapten.

Increased Production of LIGHT by T Cells in Eosinophilic Esophagitis Promotes Differentiation of Esophageal Fibroblasts Toward an Inflammatory Phenotype.

Background & Aims: Eosinophilic esophagitis (EoE) is an antigen-mediated eosinophilic disease of the esophagus that involves fibroblast activation and progression to fibrostenosis. Cytokines produced by T-helper type 2 cells and transforming growth factor beta 1 (TGFβ1) contribute to the development of EoE, but other cytokines involved in pathogenesis are unknown. We investigate the effects of tumor necrosis factor superfamily member 14 (TNFSF14, also called LIGHT) on fibroblasts in EoE.

Postpartum perineal pain and dyspareunia related to each superficial perineal muscle injury: a cohort study.

Objective: To assess the association between superficial perineal muscle trauma and perineal pain and dyspareunia.

Materials And Methods: Prospective cohort study of 405 women with a spontaneous vaginal birth comparing an intact perineum and first-degree perineal trauma group (n = 205) with a second-degree perineal trauma and episiotomy group (n = 200). Perineal pain was measured at 2 days, 10 days, 7 weeks, 3 months and 6 months postpartum.

TGFβ1 single-nucleotide polymorphism C-509T alters mucosal cell function in pediatric eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic Th2 antigen-driven disorder associated with tissue remodeling. Inflammation and remodeling lead to esophageal rigidity, strictures, and dysphagia. TGFβ1 drives esophageal remodeling including epithelial barrier dysfunction and subepithelial fibrosis.

The incidence of wound infection and dehiscence following childbirth-related perineal trauma: A systematic review of the evidence.

Objectives: Approximately 85% of vaginal births are affected by childbirth related perineal trauma, either spontaneously or as a result of an episiotomy. Perineal infection in the postnatal period is associated with wound dehiscence, granulation tissue formation, dyspareunia and pelvic floor dysfunction. Despite leading to long-term physical and psychological problems, the incidence of infection continues to remain unclear.

Incidence of perineal pain and dyspareunia following spontaneous vaginal birth: a systematic review and meta-analysis.

Introduction And Hypothesis: Perineal pain and dyspareunia are experienced by women undergoing a vaginal birth that can have short and longer term physical and psychological morbidities. This review aimed to determine the incidence of perineal pain and dyspareunia following spontaneous vaginal birth (SVB) with intact perineum, first and second-degree perineal trauma or episiotomy.

Methods: Searches of MEDLINE, EMBASE, CINAHL, AMED and MIDIRS (inception - December 2017) were undertaken with selection criteria of any study evaluating the effect of intact perineum, first- or second-degree perineal trauma on perineal pain or dyspareunia in women with SVB.

Pharmacologic inhibition of hypoxia-inducible factor (HIF)-hydroxylases ameliorates allergic contact dermatitis.

Background: When an immune cell migrates from the bloodstream to a site of chronic inflammation, it experiences a profound decrease in microenvironmental oxygen levels leading to a state of cellular hypoxia. The hypoxia-inducible factor-1α (HIF-1α) promotes an adaptive transcriptional response to hypoxia and as such is a major regulator of immune cell survival and function. HIF hydroxylases are the family of oxygen-sensing enzymes primarily responsible for conferring oxygen dependence upon the HIF pathway.

Hypoxia Inducible Factor (HIF) Hydroxylases as Regulators of Intestinal Epithelial Barrier Function.

Human health is dependent on the ability of the body to extract nutrients, fluids, and oxygen from the external environment while at the same time maintaining a state of internal sterility. Therefore, the cell layers that cover the surface areas of the body such as the lung, skin, and gastrointestinal mucosa provide vital semipermeable barriers that allow the transport of essential nutrients, fluid, and waste products, while at the same time keeping the internal compartments free of microbial organisms. These epithelial surfaces are highly specialized and differ in their anatomic structure depending on their location to provide appropriate and effective site-specific barrier function.

Impact of subsequent birth and delivery mode for women with previous OASIS: systematic review and meta-analysis.

Introduction And Hypothesis: Obstetric anal sphincter injuries (OASIS) are serious complications of vaginal birth. In a pregnancy following OASIS women may be keen to avoid an elective caesarean section, yet cautious about pursuing another vaginal birth that may result in further damage to the pelvic floor and possible long-term anal incontinence. This review aimed to evaluate the impact of subsequent birth and its mode on anal incontinence (AI) and/or quality of life (QoL), for women with previous OASIS.

Patient perception of methadone dose adequacy in methadone maintenance treatment: The role of perceived participation in dosage decisions.

Objective: In clinical practice, methadone maintenance treatment (MMT) entails tailoring the methadone dose to the patient's specific needs, thereby individualizing treatment. The aim of this study was to identify the independent factors that may significantly explain methadone dose adequacy from the patient's perspective.

Method: Secondary analysis of data collected in a treatment satisfaction survey carried out among a representative sample of MMT patients (n=122) from the region of La Rioja (Spain).