Safety and Durability of Accelerated Infliximab Dosing Strategies in Pediatric IBD: A Single Center, Retrospective Study.

Objectives: Infliximab (IFX) is commonly used to treat children with inflammatory bowel disease (IBD). We previously reported that patients with extensive disease started on IFX at a dose of 10 mg/kg had greater treatment durability at year one. The aim of this follow-up study is to assess the long-term safety and durability of this dosing strategy in pediatric IBD.

Comparison of different doses of atracurium for quality of muscle relaxation during modified rapid sequence induction in emergency laparotomy: A prospective randomised double blind study.

Background And Aims: In emergency and non-fasting patients posted for laparotomy under general anaesthesia, rapid sequence induction (RSI) is preferred, and it is routinely done by using succinylcholine or rocuronium. Using higher doses of atracurium [i.e.

Sweet's syndrome in the setting of newly initiated risankizumab therapy for pre-existing psoriasis.

Sweet's syndrome (acute febrile neutrophilic dermatosis) is a rare disorder of unclear aetiology characterised by painful cutaneous lesions, sometimes accompanied by systemic symptoms. It has been associated with several autoimmune conditions, drugs, malignancies and infections, though many cases are idiopathic. We describe a case of Sweet's syndrome in a 49-year-old man with pre-existing psoriasis following recent initiation of risankizumab therapy.

50 Years of Women in Cell Biology: Where have we been? Where are we going?

It's been 50 years since Women in Cell Biology (WICB) was founded by junior women cell biologists who found themselves neither represented at the American Society for Cell Biology (ASCB) presentations nor receiving the information, mentoring, and sponsorship they needed to advance their careers. Since then, gender parity at ASCB has made significant strides: WICB has become a standing ASCB committee, women are regularly elected president of the ASCB, and half the symposia speakers are women. Many of WICB's pioneering initiatives for professional development, including career panels, workshops, awards for accomplishments in science and mentoring, and career mentoring roundtables, have been incorporated and adapted into broader "professional development" that benefits all members of ASCB.

[Metformin Therapy During Surgical Interventions and Iodinated Contrast Agent Use].

Metformin as first-line treatment in type 2 diabetes mellitus (T2 D) shows benefits in terms of reducing cardiovascular events, but the risk of a lactic acidosis as a serious adverse event especially in patients with decreased renal function is still relevant. Since the perioperative management of Metformin or its use in diagnostic procedures with contrast agents is inconsistent in literature and different in practice, the results of various guidelines are reviewed below showing the current state of evidence. Despite many guidelines, the evidence on both issues is low, as they are mainly based on consensus recommendations.

The Science and Value of Diversity: Closing the Gaps in Our Understanding of Inclusion and Diversity.

Diversity drives excellence. Diversity enhances innovation in biomedical sciences and, as it relates to novel findings and treatment of diverse populations, in the field of infectious diseases. There are many obstacles to achieving diversity in the biomedical workforce, which create challenges at the levels of recruitment, retention, education, and promotion of individuals.

Analysis of a capped carbon nanotube by linear-scaling density-functional theory.

The apex region of a capped (5,5) carbon nanotube (CNT) has been modelled with the DFT package ONETEP, using boundary conditions provided by a classical calculation with a conducting surface in place of the CNT. Results from the DFT solution include the Fermi level and the physical distribution and energies of individual orbitals for the CNT tip. Application of an external electric field changes the orbital number of the highest occupied molecular orbital (HOMO) and consequently changes its distribution on the CNT.

Histological features of ileitis differentiating pediatric Crohn disease from ulcerative colitis with backwash ileitis.

Background/aim: Pediatric ileocolonic Crohn disease (CD) may be difficult to distinguish from ulcerative colitis (UC) with backwash ileitis (BWI). The primary aim of the study was to determine the probability of CD in children with a confluent colitis and ileitis when newly diagnosed with inflammatory bowel disease (IBD).

Methods: A retrospective observational study of 100 newly diagnosed patients with IBD was performed.

Comparison of ultrasound and anatomical landmark-guided technique for superior laryngeal nerve block to aid awake fibre-optic intubation: A prospective randomised clinical study.

Background And Aims: Ultrasonography has emerged as a novel, portable, non-invasive tool encouraging airway assessment and procedural interventions. This study assesses the feasibility of ultrasound for block of internal branch of superior laryngeal nerve (ibSLN) block during upper airway anaesthesia to aid awake fibre-optic intubation.

Methods: Forty American Society of Anesthesiologists' physical status I-II patients, aged 18-60 years, deemed to have a difficult airway (modified Mallampati class III-IV or inter-incisor distance <2.

Invisible woman?

The number of invited women speakers at scientific meetings is much less than their proportion in a field. This means that women have fewer venues to present their research, less opportunity to increase their professional network, and smaller chances of promotion and financial support. The paucity of women speakers also sends a message to aspiring young female researchers that there is no room for them at the top.

Immune tolerance. Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4⁺ T cells.

Inflammatory CD4(+) T cell responses to self or commensal bacteria underlie the pathogenesis of autoimmunity and inflammatory bowel disease (IBD), respectively. Although selection of self-specific T cells in the thymus limits responses to mammalian tissue antigens, the mechanisms that control selection of commensal bacteria-specific T cells remain poorly understood. Here, we demonstrate that group 3 innate lymphoid cell (ILC3)-intrinsic expression of major histocompatibility complex class II (MHCII) is regulated similarly to thymic epithelial cells and that MHCII(+) ILC3s directly induce cell death of activated commensal bacteria-specific T cells.

Physostigmine reverses disturbances of the intestinal microcirculation during experimental endotoxemia.

Intestinal microcirculatory disturbances play an important role in the pathophysiology of sepsis. A neural anti-inflammatory pathway has been suggested as a potential target for therapy that may dampen systemic inflammation. The aim of this study is to investigate the effects of physostigmine, a cholinesterase inhibitor, on the intestinal microcirculation and vascular contractility in experimental endotoxemia.

Mutations in PDGFRB cause autosomal-dominant infantile myofibromatosis.

Infantile myofibromatosis (IM) is a disorder of mesenchymal proliferation characterized by the development of nonmetastasizing tumors in the skin, muscle, bone, and viscera. Occurrence within families across multiple generations is suggestive of an autosomal-dominant (AD) inheritance pattern, but autosomal-recessive (AR) modes of inheritance have also been proposed. We performed whole-exome sequencing (WES) in members of nine unrelated families clinically diagnosed with AD IM to identify the genetic origin of the disorder.

Women in cell biology: a seat at the table and a place at the podium.

The Women in Cell Biology (WICB) committee of the American Society for Cell Biology (ASCB) was started in the 1970s in response to the documented underrepresentation of women in academia in general and cell biology in particular. By coincidence or causal relationship, I am happy to say that since WICB became a standing ASCB committee, women have been well represented in ASCB's leadership and as symposium speakers at the annual meeting. However, the need to provide opportunities and information useful to women in developing their careers in cell biology is still vital, given the continuing bias women face in the larger scientific arena.

NSAID-derived γ-secretase modulation requires an acidic moiety on the carbazole scaffold.

Modulation of γ-secretase activity holds potential for the treatment of Alzheimer's disease. Most NSAID-derived γ-secretase modulators feature a carboxylic acid, which may impair blood-brain barrier permeation. The structure activity relationship of 33 carbazoles featuring diverse carboxylic acid isosteres or metabolic precursors thereof was established in a cellular amyloid secretion assay.

TGF-β-stimulated CTGF production enhanced by collagen and associated with biogenesis of a novel 31-kDa CTGF form in human corneal fibroblasts.

Purpose: Connective tissue growth factor (CTGF) is induced by transforming growth factor-beta (TGF-β) after corneal wounding. This study addressed the role of the extracellular matrix in the induction of CTGF by TGF-β.

Methods: Human corneal fibroblasts (HCFs) were grown on fibronectin (FN), vitronectin (VN), or collagen (CL) in supplemented serum-free media alone or with TGF-β1 or fibroblast growth factor plus heparin.

Urokinase receptor cleavage: a crucial step in fibroblast-to-myofibroblast differentiation.

Fibroblasts migrate into and repopulate connective tissue wounds. At the wound edge, fibroblasts differentiate into myofibroblasts, and they promote wound closure. Regulated fibroblast-to-myofibroblast differentiation is critical for regenerative healing.

Localization of ZO-1 in the nucleolus of corneal fibroblasts.

Purpose: Within the multidomain structure of ZO-1 are motifs responsible for ZO-1's localization to intercellular junctions and its newly demonstrated localization to the leading edge of lamellipodia in corneal fibroblasts. Since ZO-1 also has two nuclear localization signals, this study was undertaken to determine whether stimuli associated with wounding would induce nuclear translocation of ZO-1

Methods: Immunocytochemistry and immunoblot analysis were used to localize endogenous and exogenous ZO-1 in nuclear and cytoplasmic sites in corneal fibroblasts and 293T fibroblasts, with and without myc-ZO-1 transfection. Cells were serum starved by growth for 48 hours in DMEM/F12 with 0.

FAK-dependent regulation of myofibroblast differentiation.

Fibroblasts and myofibroblasts both participate in wound healing. Transforming growth factor beta (TGFbeta) induces fibroblasts to differentiate into myofibroblasts, whereas fibroblast growth factor and heparin (FGF/h) induce myofibroblasts to "de-differentiate" into fibroblasts. TGFbeta induces expression of smooth muscle alpha actin (SMalphaA) and incorporation into in stress fibers, a phenotype of differentiated myofibroblasts.

Connective tissue growth factor (CTGF) expression in the brain is a downstream effector of insulin resistance- associated promotion of Alzheimer's disease beta-amyloid neuropathology.

The goal of this study was to further explore potential mechanisms through which diabetogenic dietary conditions that result in promotion of insulin resistance (IR), a feature of non-insulin dependant diabetes mellitus (type-2 diabetes), may influence Alzheimer's disease (AD). Using genome-wide array technology, we found that connective tissue growth factor (CTGF), a gene product described previously for its involvement in diabetic fibrosis, is elevated in brain tissue in an established mouse model of diet-induced IR. With this evidence we continued to explore the regulation of CTGF in postmortem AD brain tissue and found that CTGF expression correlated with the progression of AD clinical dementia and amyloid neuritic plaque (NP) neuropathology, but not neurofibrillary tangle (NFT) deposition.

ZO-1: lamellipodial localization in a corneal fibroblast wound model.

Purpose: To explore the roles of ZO-1 in corneal fibroblasts and myofibroblasts in a model of wounding.

Methods: Antibodies were used to identify ZO-1 in cultured rabbit corneal fibroblasts by immunocytochemistry, Western blot analysis, and immunoprecipitation. For colocalization studies, antibodies to beta-catenin, cadherins, connexins, integrins, alpha-actinin, and cortactin were used.

Urokinase anchors uPAR to the actin cytoskeleton.

Purpose: To investigate the expression and localization of urokinase plasminogen activator (uPA) and its receptor (uPAR) and their interaction with the actin cytoskeleton in human corneal fibroblasts.

Methods: Primary cultured human corneal fibroblasts were exposed to exogenous uPA to investigate its effect on the distribution of uPAR under resting conditions and in a scrape-wound model. Fluorescence microscopy, immunolocalization, immunoprecipitation, and the actin depolymerizing drug cytochalasin D were used to evaluate uPAR's interaction with the actin cytoskeleton.

Involvement of S100A4 in stromal fibroblasts of the regenerating cornea.

Purpose: S100A4 is a member of the S100 family of calcium-binding proteins. Members of the S100 family have been implicated in a variety of cellular events, including growth, signaling, differentiation, and motility. It has been suggested that S100A4 modulates cell shape and motility by interacting with components of the cytoskeleton.

Endothelin-converting enzyme inhibition ameliorates angiotensin II-induced cardiac damage.

We tested the hypothesis that endothelin-converting enzyme (ECE) inhibition ameliorates end-organ damage in rats harboring both human renin and human angiotensinogen genes (dTGR). Hypertension develops in the animals, and they die by age 7 weeks of heart and kidney failure. Three groups were studied: dTGR (n=12) receiving vehicle, dTGR receiving ECE inhibitor (RO0687629; 30 mg/kg by gavage; n=10), and Sprague-Dawley control rats (SD; n=10) receiving vehicle, all after week 4, with euthanasia at week 7.