Brief Pain Inventory (BPI) Pain Survey Cysteine Protease Caspase-1 (Casp1) Blood Levels Following Midline Laparotomy: A Prospective Randomized Study of Patients With Benign Disease and Patients With Cancer.

Background/aim: There is lack of studies assessing the correlation between pain scales and acute phase immune response (APR) following surgery. The purpose of this work was to assess the correlation between cysteine protease caspase-1 (Casp1) blood levels and two pain scales in a cohort of 56 midline laparotomy (MLa) patients and to assess their link with other cytokines (CYTs).

Patients And Methods: Blood levels of Casp1 and other CYTs (IL-18, IL-18BP, IL-1ra, IL-6, IL-8, IL-10, IL-1β) were measured before operation and following surgery in patients with MLa.

Correlation Between Blood Levels of Cysteine Protease Caspase-1 (Casp1) and Pain Scores (NRS) Post-surgery: A Prospective Randomized Study of Patients With Cholelithiasis.

Background/aim: Cysteine protease caspase-1 (Casp1) plays a crucial role in the conversion of pro-cytokines to active cytokines (CYTs). The purpose of this work was to determine Casp1 blood levels in a cohort of 114 cholecystectomy patients and assess their association with other CYTs and numeric rating scale (NRS) pain scores, postoperatively.

Patients And Methods: Blood levels of Casp1 and seven CYTs (IL-18, IL-18BP, IL-1ra, IL-6, IL-10, IL-1β, and IL-8) were measured at three time points; before operation, immediately after operation, and six hours after operation in 114 patients with cholelithiasis (Chole).

DNA methylation differences within , and promoters in lymphocyte subsets in children with type 1 diabetes and controls.

We elucidated the effect of four known T1D-susceptibility associated single nucleotide polymorphism (SNP) markers in three genes (rs12722495 and rs2104286 in , rs689 in and rs2476601 in ) on CpG site methylation of their proximal promoters in different lymphocyte subsets using pyrosequencing. The study cohort comprised 25 children with newly diagnosed T1D and 25 matched healthy controls. The rs689 SNP was associated with methylation at four CpG sites in promoter: -234, -206, -102 and -69.

Technical Validation and Utility of an HLA Class II Tetramer Assay for Type 1 Diabetes: A Multicenter Study.

Context: Validated assays to measure autoantigen-specific T-cell frequency and phenotypes are needed for assessing the risk of developing diabetes, monitoring disease progression, evaluating responses to treatment, and personalizing antigen-based therapies.

Objective: Toward this end, we performed a technical validation of a tetramer assay for HLA-DRA-DRB1*04:01, a class II allele that is strongly associated with susceptibility to type 1 diabetes (T1D).

Methods: HLA-DRA-DRB1*04:01-restricted T cells specific for immunodominant epitopes from islet cell antigens GAD65, IGRP, preproinsulin, and ZnT8, and a reference influenza epitope, were enumerated and phenotyped in a single staining tube with a tetramer assay.

A Possible Role of Interleukin-18 Binding Protein in Immune Regulation of Postoperative Pain: A Prospective Randomized Clinical Trial.

Background/aim: A possible role of interleukin-18 binding protein (IL-18BP) in immune regulation of pain and analgesics following surgery is rarely studied. The aim of this study was to investigate serum IL-18BP values in a cohort of laparoscopic cholecystectomy (LC) and minilaparotomy cholecystectomy (MC) patients and to establish their relationship with other cytokines and number of analgesic doses (NAD) of LC and MC patients postoperatively.

Patients And Methods: Blood levels of IL-18BP, six other interleukins (IL-18, IL-1ra, IL-6, IL-10, IL-1β, and IL-8) and high-sensitivity C-reactive protein were measured before operation (PRE), immediately after operation (POP1), and six hours after operation (POP2) in 114 patients with cholelithiasis.

Skin, gut, and sand metagenomic data on placebo-controlled sandbox biodiversity intervention study.

The metagenomic data presented in this article are related to the published research of "A Placebo-controlled double-blinded test of the biodiversity hypothesis of immune-mediated diseases: Environmental microbial diversity elicits changes in cytokines and increase in T regulatory cells in young children" This database contains 16S ribosomal RNA (rRNA) metagenomics of sandbox sand and skin and gut microbiota of children in the intervention and placebo daycares. In intervention daycares, children aged 3-5 years were exposed to playground sand enriched with microbially diverse soil. In placebo daycares, children were exposed to visually similar as in intervention daycares, but microbially poor sand colored with peat.

Interleukin-18 (IL-18) Cytokine Serum Concentrations Correlate With Pain Scores and the Number of Analgesic Doses Following Surgery.

Background/aim: Anti- and proinflammatory cytokines and plasma high-sensitivity C-reactive protein (hs-CRP) are used to assess inflammatory stress response (ISR) following surgery. However, the serum IL-18 (interleukin-18) cytokine values versus numeric rating scale (NRS) pain score and number of analgesic doses (NAD) postoperatively are unknown.

Patients And Methods: Blood levels of six interleukins (IL-18, IL-1ra, IL-6, IL-10, IL-1β, and IL-8) and hs-CRP were measured at three time points; before operation (PRE), immediately after operation (POP1), and six hours after operation (POP2) in 114 patients with cholelithiasis.

A Placebo-controlled double-blinded test of the biodiversity hypothesis of immune-mediated diseases: Environmental microbial diversity elicits changes in cytokines and increase in T regulatory cells in young children.

Background: According to the biodiversity hypothesis of immune-mediated diseases, lack of microbiological diversity in the everyday living environment is a core reason for dysregulation of immune tolerance and - eventually - the epidemic of immune-mediated diseases in western urban populations. Despite years of intense research, the hypothesis was never tested in a double-blinded and placebo-controlled intervention trial.

Objective: We aimed to perform the first placebo-controlled double-blinded test that investigates the effect of biodiversity on immune tolerance.

Single-cell characterization of dog allergen-specific T cells reveals T2 heterogeneity in allergic individuals.

Background: Allergen-specific type 2 CD4 T2 cells are critically involved in the pathogenesis of IgE-mediated allergic diseases. However, the heterogeneity of the T2 response has only recently been appreciated.

Objective: We sought to characterize at the single-cell level the ex vivo phenotype, transcriptomic profile, and T-cell receptor (TCR) repertoire of circulating CD4 T cells specific to the major dog allergens Can f 1, Can f 4, and Can f 5 in subjects with and without dog allergy.

Generation of self-reactive, shared T-cell receptor α chains in the human thymus.

The T-cell receptor (TCR) repertoire is generated in a semistochastic process of gene recombination and pairing of TCRα to TCRβ chains with the estimated total TCR diversity of >10. Despite this high diversity, similar or identical TCR chains are found to recur in immune responses. Here, we analyzed the thymic generation of TCR sequences previously associated with recognition of self- and nonself-antigens, represented by sequences associated with autoimmune diabetes and HIV, respectively.

Biodiversity intervention enhances immune regulation and health-associated commensal microbiota among daycare children.

As the incidence of immune-mediated diseases has increased rapidly in developed societies, there is an unmet need for novel prophylactic practices to fight against these maladies. This study is the first human intervention trial in which urban environmental biodiversity was manipulated to examine its effects on the commensal microbiome and immunoregulation in children. We analyzed changes in the skin and gut microbiota and blood immune markers of children during a 28-day biodiversity intervention.

Mucosal-associated invariant T cell alterations during the development of human type 1 diabetes.

Aims/hypothesis: Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognise derivatives of bacterial riboflavin metabolites presented by MHC-Ib-related protein 1 (MR1) molecules and are important effector cells for mucosal immunity. Their development can be influenced by the intestinal microbiome. Since the development of type 1 diabetes has been associated with changes in the gut microbiome, this can be hypothesised to lead to alterations in circulating MAIT cells.

B cell helper T cells and type 1 diabetes.

Type 1 diabetes is an autoimmune disease typically starting in childhood that culminates in the destruction of insulin-producing beta cells in the pancreas. Although type 1 diabetes is considered to be a primarily T cell-mediated disease, B cells clearly participate in the autoimmune process, as autoantibodies recognizing pancreatic islet antigen commonly appear in circulation before the onset of the disease. T cells providing helper functions to B cells have recently been shown to be involved in the pathogenesis of a wide range of antibody-associated immune disorders.

Characterization of Proinsulin T Cell Epitopes Restricted by Type 1 Diabetes-Associated HLA Class II Molecules.

Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease in which the insulin-producing β cells within the pancreas are destroyed. Identification of target Ags and epitopes of the β cell-reactive T cells is important both for understanding T1D pathogenesis and for the rational development of Ag-specific immunotherapies for the disease. Several studies suggest that proinsulin is an early and integral target autoantigen in T1D.

Type 1 diabetes linked PTPN22 gene polymorphism is associated with the frequency of circulating regulatory T cells.

Dysfunction of FOXP3-positive regulatory T cells (Tregs) likely plays a major role in the pathogenesis of multiple autoimmune diseases including type 1 diabetes (T1D). Whether genetic polymorphisms associated with the risk of autoimmune diseases affect Treg frequency or function is currently unclear. Here, we analysed the effect of T1D-associated major HLA class II haplotypes and seven single nucleotide polymorphisms in six non-HLA genes [INS (rs689), PTPN22 (rs2476601), IL2RA (rs12722495 and rs2104286), PTPN2 (rs45450798), CTLA4 (rs3087243), and ERBB3 (rs2292239)] on peripheral blood Treg frequencies.

Circulating CXCR5PD-1 peripheral T helper cells are associated with progression to type 1 diabetes.

Aims/hypothesis: Type 1 diabetes is preceded by a period of asymptomatic autoimmunity characterised by positivity for islet autoantibodies. Therefore, T helper cell responses that induce B cell activation are likely to play a critical role in the disease process. Here, we aimed to evaluate the role of a recently described subset, C-X-C motif chemokine receptor type 5-negative, programmed cell death protein 1-positive (CXCR5PD-1) peripheral T helper (Tph) cells, in human type 1 diabetes.

FOXP3+ Regulatory T Cell Compartment Is Altered in Children With Newly Diagnosed Type 1 Diabetes but Not in Autoantibody-Positive at-Risk Children.

The dysfunction of FOXP3-positive regulatory T cells (Tregs) plays a key role in the pathogenesis of autoimmune diseases, including type 1 diabetes (T1D). However, previous studies analyzing the peripheral blood Treg compartment in patients with T1D have yielded partially conflicting results. Moreover, the phenotypic complexity of peripheral blood Tregs during the development of human T1D has not been comprehensively analyzed.

Mast Cells Are a Marked Source for Complement C3 Products That Associate with Increased CD11b-Positive Cells in Keratinocyte Skin Carcinomas.

By using immunohistochemistry and antibodies that identify complement C3c (in C3 and C3b) or CD11b receptor, we report that the proportion C3c mast cells and the number of CD11b cells are increased in basal cell carcinoma (BCC). Instead, only CD11b cells are increased in squamous cell carcinoma/Bowen's disease, and only slightly so in actinic keratosis. Only C3c mast cells are increased in psoriasis.

Circulating levels of microRNA 423-5p are associated with 90 day mortality in cardiogenic shock.

Aims: The role of microRNAs has not been studied in cardiogenic shock. We examined the potential role of miR-423-5p level to predict mortality and associations of miR-423-5p with prognostic markers in cardiogenic shock.

Methods And Results: We conducted a prospective multinational observational study enrolling consecutive cardiogenic shock patients.

Early childhood CMV infection may decelerate the progression to clinical type 1 diabetes.

Aims/hypothesis: Evidence of the role of cytomegalovirus (CMV) infection in the pathogenesis of type 1 diabetes (T1D) has remained inconclusive. Our aim was to elucidate the possible role of CMV infection in the initiation of islet autoimmunity and in the progression to clinical T1D among children with human leukocyte antigen (HLA)-conferred T1D risk.

Methods: A total of 1402 children from the prospective Type 1 Diabetes Prediction and Prevention (DIPP) study were analyzed for CMV-specific IgG antibodies during early childhood.

The combination of TRAIL and MG-132 induces apoptosis in both TRAIL-sensitive and TRAIL-resistant human follicular lymphoma cells.

We have previously shown that the human follicular lymphoma cell line, HF28GFP, is sensitive to TRAIL-mediated apoptosis. Nevertheless, when the same cells overexpress anti-apoptotic Bcl-2 family protein, Bcl-xL (HF28Bcl-xL), they become resistant to TRAIL. Thus, these cell lines help us to investigate the action of novel apoptosis inducing candidate drugs.

Camelina Sativa Oil, but not Fatty Fish or Lean Fish, Improves Serum Lipid Profile in Subjects with Impaired Glucose Metabolism-A Randomized Controlled Trial.

Scope: The aim of the study is to examine whether lean fish (LF), fatty fish (FF), and camelina sativa oil (CSO), a plant-based source of alpha-linolenic acid (ALA), differ in their metabolic effects in subjects with impaired glucose metabolism.

Methods And Results: Altogether 79 volunteers with impaired fasting glucose, BMI 25-36 kg m , age 43-72 years, participated in a 12-week randomized controlled trial with four parallel groups, that is, the FF (four fish meals/week), LF (four fish meals/week), CSO (10 g d ALA), and control (limited intakes of fish and sources of ALA) groups. The proportions of eicosapentaenoic acid and DHA increase in plasma lipids in the FF group, and the proportion of ALA increase in the CSO group (p < 0.

Frequency and Prognostic Significance of Abnormal Liver Function Tests in Patients With Cardiogenic Shock.

Cardiogenic shock (CS) is a cardiac emergency often leading to multiple organ failure and death. Assessing organ dysfunction and appropriate risk stratification are central for the optimal management of these patients. The purpose of this study was to assess the prevalence of abnormal liver function tests (LFTs), as well as early changes of LFTs and their impact on outcome in CS.

RIP1 has a role in CD40-mediated apoptosis in human follicular lymphoma cells.

CD40 is a cell surface receptor which belongs to tumor necrosis factor receptor (TNFR) family members. It transmits signals that regulate diverse cellular responses such as proliferation, differentiation, adhesion molecule expression and apoptosis. Unlike other TNFR family members (TRAIL-R, Fas-R and TNFR1), the CD40 cytoplasmic tail lacks death domain.

Timing determines dexamethasone and rituximab induced synergistic cell death.

Dysregulation of cell death signaling pathways in many cell types such as B lymphocytes (B-cells) can lead to cancer, for example to B-cell lymphomas. Rituximab (RTX) and glucocorticoids such as dexamethasone (Dex) are widely used to treat hematological malignancies including B-cell lymphomas. Although the combination of Dex and RTX improves the treatment outcome of lymphoma patients, most lymphomas remain incurable diseases.