Activated CD27PD-1 CD8 T Cells and CD4 T Regulatory Cells Dominate the Tumor Microenvironment in Refractory Celiac Disease Type II.

Background And Aims: Refractory celiac disease type II (RCDII) is characterized by a clonally expanded aberrant cell population in the small intestine. The role of other tissue-resident immune subsets in RCDII is unknown. Here, we characterized CD8 and CD4 T cells in RCDII duodenum at the single-cell level and .

G-quadruplex stabilization provokes DNA breaks in human PKD1, revealing a second hit mechanism for ADPKD.

The "secondhit" pathway is responsible for biallelic inactivation of many tumor suppressors, where a pathogenic germline allele is joined by somatic mutation of the remaining functional allele. The mechanisms are unresolved, but the human PKD1 tumor suppressor is a good experimental model for identifying the molecular determinants. Inactivation of PKD1 results in autosomal dominant polycystic kidney disease, a very common disorder characterized by the accumulation of fluid-filled cysts and end-stage renal disease.

Using Participatory Narrative Inquiry to Assess Experiences and Self-Experimentation with Diet Interventions in Inflammatory Bowel Disease Patients.

Background And Aims: To improve quality of life (QoL), patients with inflammatory bowel diseases (Crohn's disease and ulcerative colitis) often self-experiment with lifestyle changes such as dietary modifications. The nature (e.g.

Surgical versus conservative treatment for odontoid fractures in older people: an international prospective comparative study.

Background: The optimal treatment for odontoid fractures in older people remains debated. Odontoid fractures are increasingly relevant to clinical practice due to ageing of the population.

Methods: An international prospective comparative study was conducted in fifteen European centres, involving patients aged ≥55 years with type II/III odontoid fractures.

Medical Malpractice in Neurosurgery: An Analysis of Claims in the Netherlands.

Background And Objectives: Studying malpractice claims is important to improve quality of health care and patient safety and to educate the individual healthcare providers. The objective of this study was to describe characteristics of neurosurgical claims in the Netherlands.

Methods: A nationwide retrospective observational study of neurosurgery-related claims closed by Centramed and MediRisk, 2 major insurance companies in the Netherlands, was performed.

Diagnostic criteria and long-term outcomes in AIH-PBC variant syndrome under combination therapy.

Background & Aims: Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) can co-exist in AIH-PBC, requiring combined treatment with immunosuppression and ursodeoxycholic acid (UDCA). The Paris criteria are commonly used to identify these patients; however, the optimal diagnostic criteria are unknown. We aimed to evaluate the use and clinical relevance of both Paris and Zhang criteria.

Methotrexate accumulation in target intestinal mucosa and white blood cells differs from non-target red blood cells of patients with Crohn's disease.

Background: Intracellular methotrexate polyglutamates (MTX-PGs) concentrations are measurable in red blood cells (RBCs) during MTX treatment. MTX-PG concentrations correlate with efficacy in patients with Crohn's disease (CD). Since RBCs are not involved in pathogenesis of CD and lack extended MTX metabolism, we determined MTX-PGs accumulation in peripheral blood mononuclear cells (PBMCs: effector cells) and intestinal mucosa (target cells) and compared those with RBCs as a potential more precise biomarker.

(Cost-)effectiveness of personalised multimodal physiotherapy compared to surgery in patients with cervical radiculopathy: A systematic review.

Rationale: Cervical radiculopathy is initially typically managed conservatively. Surgery is indicated when conservative management fails or with severe/progressive neurological signs. Personalised multimodal physiotherapy could be a promising conservative strategy.

Enduring Clinical Remission in Refractory Celiac Disease Type II With Tofacitinib: An Open-Label Clinical Study.

Refractory celiac disease type 2 (RCDII) is a rare condition with high mortality because of a lack of effective treatment strategies. RCDII is caused by clonal expansion of intraepithelial lymphocytes (IELs). Gain-of-function JAK1 mutations are frequently found in these cells.

Use of equine embryo -derived mesenchymal stromal cells and their extracellular vesicles as a treatment for persistent breeding-induced endometritis in susceptible mares.

Persistent breeding induced endometritis (PBIE) is a significant cause of infertility in mares. The development of a safe, universal, readily available therapeutic to manage PBIE and facilitate an optimal uterine environment for embryo development may improve pregnancy rates in susceptible mares. Mesenchymal stromal cells (MSCs) are being used increasingly as a therapeutic mediator for inflammatory conditions such as endometritis, and early gestational tissue provides a unique source of multipotent stem cells for creating MSCs.

The long-term outcome of revision microdiscectomy for recurrent sciatica.

Purpose: To study the long-term outcome of revision microdiscectomy after classic microdiscectomy for lumbosacral radicular syndrome (LSRS).

Methods: Eighty-eight of 216 patients (41%) who underwent a revision microdiscectomy between 2007 and 2010 for MRI disc-related LSRS participated in this study. Questionnaires included visual analogue scores (VAS) for leg pain, RDQ, OLBD, RAND-36, and seven-point Likert scores for recovery, leg pain, and back pain.

Human sequences form R-loop structures .

Autosomal dominant polycystic kidney disease results from the loss of the gene product, polycystin 1. Regulatory mechanisms are unresolved, but an apparent G/C sequence bias in the gene is consistent with co-transcriptional R-loop formation. R-loops regulate gene expression and stability, and they form when newly synthesized RNA extensively pairs with the template DNA to displace the non-template strand.

Therapeutic drug monitoring of methotrexate in patients with Crohn's disease.

Background: Therapeutic drug monitoring (TDM) has the potential to improve efficacy and diminish side effects. Measuring methotrexate-polyglutamate (MTX-PG) in erythrocytes might enable TDM for methotrexate in patients with Crohn's disease (CD).

Aim: To investigate the relationship between MTX-PGs and methotrexate drug survival, efficacy and toxicity METHODS: In a multicentre prospective cohort study, patients with CD starting subcutaneous methotrexate without biologics were included and followed for 12 months.

Standardizing Randomized Controlled Trials in Celiac Disease: An International Multidisciplinary Appropriateness Study.

Background & Aims: There is a need to develop safe and effective pharmacologic options for the treatment of celiac disease (CeD); however, consensus on the appropriate design and configuration of randomized controlled trials (RCTs) in this population is lacking.

Methods: A 2-round modified Research and Development/University of California Los Angeles Appropriateness Method study was conducted. Eighteen gastroenterologists (adult and pediatric) and gastrointestinal pathologists voted on statements pertaining to the configuration of CeD RCTs, inclusion and exclusion criteria, gluten challenge, and trial outcomes.

Lack of complete biochemical response in autoimmune hepatitis leads to adverse outcome: First report of the IAIHG retrospective registry.

Background And Aims: The International Autoimmune Hepatitis Group retrospective registry (IAIHG-RR) is a web-based platform with subjects enrolled with a clinical diagnosis of autoimmune hepatitis (AIH). As prognostic factor studies with enough power are scarce, this study aimed to ascertain data quality and identify prognostic factors in the IAIHG-RR cohort.

Methods: This retrospective, observational, multicenter study included all patients with a clinical diagnosis of AIH from the IAIHG-RR.

High-fat diet during pregnancy promotes fetal skeletal muscle fatty acid oxidation and insulin resistance in an ovine model.

Maternal diet during pregnancy is associated with offspring metabolic risk trajectory in humans and animal models, but the prenatal origins of these effects are less clear. We examined the effects of a high-fat diet (HFD) during pregnancy on fetal skeletal muscle metabolism and metabolic risk parameters using an ovine model. White-faced ewes were fed a standardized diet containing 5% fat wt/wt (CON), or the same diet supplemented with 6% rumen-protected fats (11% total fat wt/wt; HFD) beginning 2 wk before mating until midgestation (GD75).

A randomised, double-blind, placebo-controlled study of the LAG-3-depleting monoclonal antibody GSK2831781 in patients with active ulcerative colitis.

Background: Selective depletion of T cells expressing LAG-3, an immune checkpoint receptor that is upregulated on activated T cells, has been investigated in pre-clinical models as a potential therapeutic approach in inflammatory and autoimmune diseases where activated T cells are implicated.

Aims: GSK2831781, a depleting monoclonal antibody that specifically binds LAG-3 proteins, may deplete activated LAG-3 cells in ulcerative colitis (UC).

Methods: Patients with moderate to severe UC were randomised to GSK2831781 or placebo.

Corticotropin releasing hormone is present in the feline placenta and maternal serum.

Background: In women, placental corticotropin releasing hormone (CRH) can be detected in maternal blood throughout pregnancy and is important in the regulation of the timing of parturition. However, its role in other mammalian species is unclear. In fact, very little is known about the presence and localization of CRH in placentas other than human.

Cerebellar presence of immune cells in patients with neuro-coeliac disease.

Although various neurodegenerative disorders have been associated with coeliac disease (CD), the underlying neuropathological link between these brain and gut diseases remains unclear. We postulated that the neuronal damage sporadically observed in CD patients is immune-mediated. Our aim was to determine if the loss of neurons, especially Purkinje cells, coincides with microglia activation and T- and B-cell infiltration in the cerebellum of patients with CD and a concomitant idiopathic neurological disease affecting the cerebellum (NeuroCD).