Regulatory Eosinophils Suppress T Cells Partly through Galectin-10.

Eosinophils have the capacity to regulate the function of T cell subsets. Our aim was to test the hypothesis of the existence of a regulatory subset of eosinophils. Human eosinophils were incubated with T cells that were stimulated with allogeneic leukocytes or CD3/CD28 cross-linking.

Mutations in COL1A1 and COL1A2 and dental aberrations in children and adolescents with osteogenesis imperfecta - A retrospective cohort study.

Osteogenesis imperfecta (OI) is a heterogeneous group of disorders of connective tissue, caused mainly by mutations in the collagen I genes (COL1A1 and COL1A2). Dentinogenesis imperfecta (DGI) and other dental aberrations are common features of OI. We investigated the association between collagen I mutations and DGI, taurodontism, and retention of permanent second molars in a retrospective cohort of 152 unrelated children and adolescents with OI.

Real-time Characterization of Antibody Binding to Receptors on Living Immune Cells.

Understanding molecular interactions on immune cells is crucial for drug development to treat cancer and autoimmune diseases. When characterizing molecular interactions, the use of a relevant living model system is important, as processes such as receptor oligomerization and clustering can influence binding patterns. We developed a protocol to enable time-resolved analysis of ligand binding to receptors on living suspension cells.

Insights from engineering the Affibody-Fc interaction with a computational-experimental method.

The interaction between the Staphylococcal Protein A (SpA) domain B (the basis of the Affibody) molecule and the Fc of IgG is key to the use of Affibodies in affinity chromatography and in potential therapies against certain inflammatory diseases. Despite its importance and four-decade history, to our knowledge this interaction has never been affinity matured. We elucidate reasons why single-substitutions in the SpA which improve affinity to Fc may be very rare, and also discover substitutions which potentially serve several engineering purposes.

On the Site and Mechanism of Action of β-Adrenoceptor Agonists in the Bladder.

The clinical success of mirabegron as the first β-adrenoceptor (AR) agonist for treatment of the overactive bladder (OAB) syndrome, has resulted in substantial interest in its site and mechanism of action. Even if the adrenergic innervation of the bladder and urethra has been well studied, the location(s) of β-ARs in different structures within the bladder wall and urethra, and the mode(s) of action of β-AR stimulation have still not been established. The recent demonstration of β-ARs on cholinergic nerve terminals with no immunoreactivity in urothelium or detrusor smooth muscle, is not in agreement with previous morphological studies, and functional data strongly suggest that β-ARs can be found these structures.

Can incontinence be cured? A systematic review of cure rates.

Background: Incontinence constitutes a major health problem affecting millions of people worldwide. The present study aims to assess cure rates from treating urinary (UI) or fecal incontinence (FI) and the number of people who may remain dependent on containment strategies.

Methods: Medline, Embase, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, and PEDro were searched from January 2005 to June 2015.

Electrospun biodegradable microfibers induce new collagen formation in a rat abdominal wall defect model: A possible treatment for pelvic floor repair?

Half of the female population over age 50 years will experience pelvic organ prolapse. We suggest a new approach based on tissue engineering principles to functionally reconstruct the anatomical structures of the pelvic floor. The aim of this study is to investigate the mechanical performance and effect on collagen and elastin production of a degradable mesh releasing basic fibroblast growth factor (bFGF).

Association of lower urinary tract syndrome with peripheral arterial occlusive disease.

Purpose: To describe atherosclerosis may lead to chronic bladder ischemia, eventually resulting in lower urinary tract syndrome (LUTS), and peripheral arterial occlusive disease (PAOD). We investigated the association of LUTS with PAOD.

Methods: This nationwide population-based cohort study was based on data from the Taiwan National Health Insurance Database from 2000 to 2010; follow-up lasted until the end of 2011.

Allergic disease in 8-year-old children is preceded by delayed B cell maturation.

Background: We previously reported that exposure to a farming environment is allergy-protective, while high proportions of neonatal immature/naïve CD5 B cells and putative regulatory T cells (Tregs) are risk factors for development of allergic disease and sensitization up to 3 years of age.

Objective: To examine if B and T cell maturation are associated with allergic disease and farming environment over the first 8 years in life.

Methods: In the prospective FARMFLORA study, including both farming and non-farming families, 48 of 65 children took part in the 8-year follow-up study.

New Iminodiacetate-Thiosemicarbazone Hybrids and Their Copper(II) Complexes Are Potential Ribonucleotide Reductase R2 Inhibitors with High Antiproliferative Activity.

As ribonucleotide reductase (RNR) plays a crucial role in nucleic acid metabolism, it is an important target for anticancer therapy. The thiosemicarbazone Triapine is an efficient R2 inhibitor, which has entered ∼20 clinical trials. Thiosemicarbazones are supposed to exert their biological effects through effectively binding transition-metal ions.

Wholegrain oat diet changes the expression of genes associated with intestinal bile acid transport.

Scope: The molecular mechanisms underlying the cholesterol-lowering properties of oats are only partly known. To study possible pathways involved, we investigated gene expressions in the liver and small intestine of mice fed oats.

Method And Results: Cholesterol and bile acids were analyzed in plasma and feces from LDL-receptor deficient (LDLr ) mice fed Western diet with wholegrain oats.

Bladder Capacity is a Biomarker for a Bladder Centric versus Systemic Manifestation in Interstitial Cystitis/Bladder Pain Syndrome.

Purpose: Interstitial cystitis/bladder pain syndrome presents a significant clinical challenge due to symptom heterogeneity and the myriad associated comorbid medical conditions. We recently reported that diminished bladder capacity may represent a specific interstitial cystitis/bladder pain syndrome subphenotype. The objective of this study was to investigate the relationship between anesthetic bladder capacity, and urological and nonurological clinical findings in a cohort of patients with interstitial cystitis/bladder pain syndrome who had undergone therapeutic urinary bladder hydrodistention.

Blood chemokine profile in untreated early rheumatoid arthritis: CXCL10 as a disease activity marker.

Background: We have recently analyzed the profile of T-cell subtypes based on chemokine receptor expression in blood from untreated early rheumatoid arthritis (ueRA) patients compared to healthy controls (HC). Here, we compared the levels of the respective chemokines in blood plasma of ueRA patients with those of HC. We also studied the association of chemokine levels with the proportions of circulating T-cell subsets and the clinical disease activity.

A Belief Rule Based Expert System to Assess Tuberculosis under Uncertainty.

The primary diagnosis of Tuberculosis (TB) is usually carried out by looking at the various signs and symptoms of a patient. However, these signs and symptoms cannot be measured with 100 % certainty since they are associated with various types of uncertainties such as vagueness, imprecision, randomness, ignorance and incompleteness. Consequently, traditional primary diagnosis, based on these signs and symptoms, which is carried out by the physicians, cannot deliver reliable results.

Smoking activates cytotoxic CD8 T cells and causes survivin release in rheumatoid arthritis.

CD8 T cells have an emerging role in RA. Resent research indicates a causal relationship between the non-exhausted state of CD8 T cells, defined by lost function of PD-1, and development of arthritis. We investigated how smoking contributes to the non-exhausted phenotype of CD8 T cells and cause survivin release to serum.

Clock Genes Regulate the Circadian Expression of Piezo1, TRPV4, Connexin26, and VNUT in an Ex Vivo Mouse Bladder Mucosa.

Objectives: ClockΔ19/Δ19 mice is an experimental model mouse for nocturia (NOC). Using the bladder mucosa obtained from ClockΔ19/Δ19 mice, we investigated the gene expression rhythms of mechanosensory cation channels such as transient receptor potential cation channel subfamily V member 4 (TRPV4) and Piezo1, and main ATP release pathways including vesicular nucleotide transporter (VNUT) and Connexin26(Cx26), in addition to clock genes.

Materials And Methods: Eight- to twelve-week-old male C57BL/6 mice (WT) and age- and sex-matched C57BL/6 ClockΔ19/Δ19 mice, which were bred under 12-h light/dark conditions for 2 weeks, were used.

IFN type I and II induce BAFF secretion from human decidual stromal cells.

B cell activating factor (BAFF) is a critical cytokine for maturation of immature B cells. In murine lymph nodes, BAFF is mainly produced by podoplanin-expressing stromal cells. We have previously shown that circulating BAFF levels are maximal at birth, and that farmers' children exhibit higher BAFF levels in cord blood than non-farmers' children.

Determinates of muscle precursor cell therapy efficacy in a nonhuman primate model of intrinsic urinary sphincter deficiency.

Background: Cell therapy for intrinsic urinary sphincter deficiency (ISD) in women has been moderately effective, and improvements are needed. To improve treatment efficacy, it is important to better understand determinates of cell efficacy in the different patient cohorts. We have reported that in nonhuman primates the chronicity of ISD may affect cell efficacy, but additional factors (age, psychosocial stress, hormone status, body weight) can be associated with many disease/treatment outcomes in women - and these factors are the focus of this study.

The link between vascular dysfunction, bladder ischemia, and aging bladder dysfunction.

The vascular supply to the human bladder is derived mainly from the superior and inferior vesical arteries, the latter being directly connected to the internal iliac artery. Aging is associated with an impairment of blood vessel function and changes may occur in the vasculature at the molecular, cellular and functional level. Pelvic arterial insufficiency may play an important role in the development of bladder dysfunctions such as detrusor overactivity (DO) and the overactive bladder syndrome.

Lupus-like Immune Complex-mediated Glomerulonephritis in Patients with Hepatitis C Virus Infection Treated with Oral, Interferon-free, Direct-acting Antiviral Therapy.

Novel, all-oral interferon-free direct-acting antiviral agents have revolutionized the management of hepatitis C virus (HCV) infection by producing exceptional cure rates with minimal adverse events. While provocation or exacerbation of autoimmunity has been reported in HCV-infected patients receiving interferon, this phenomenon has not been reported in patients receiving interferon-free HCV therapy. We report the occurrence of three cases of lupus-like immune complex-mediated glomerulonephritis occurring shortly after exposure to sofosbuvir-based direct-acting antiviral therapies.

Thermodynamic and kinetic approaches for evaluation of monoclonal antibody - Lipoprotein interactions.

Two complementary instrumental techniques were used, and the data generated was processed with advanced numerical tools to investigate the interactions between anti-human apoB-100 monoclonal antibody (anti-apoB-100 Mab) and apoB-100 containing lipoproteins. Partial Filling Affinity Capillary Electrophoresis (PF-ACE) combined with Adsorption Energy Distribution (AED) calculations provided information on the heterogeneity of the interactions without any a priori model assumptions. The AED calculations evidenced a homogenous binding site distribution for the interactions.

Decentralization can help reduce deforestation when user groups engage with local government.

Policy makers around the world tout decentralization as an effective tool in the governance of natural resources. Despite the popularity of these reforms, there is limited scientific evidence on the environmental effects of decentralization, especially in tropical biomes. This study presents evidence on the institutional conditions under which decentralization is likely to be successful in sustaining forests.

Survivin controls biogenesis of microRNA in smokers: A link to pathogenesis of rheumatoid arthritis.

MicroRNAs (miRs) represent a part of epigenetic control of autoimmunity gaining increasing attention in rheumatoid arthritis (RA). Since cigarette smoking plays important role in RA pathogenesis and reprograms transcriptional profile of miRNAs, we ask if the onco-protein survivin, a novel biomarker of RA, may provide a link between smoking and miRNA. Studying survivin expression in leukocytes of 144 female RA patients we observed that smoking patients had higher survivin transcription and a remarkable spreading of survivin isoforms.