Immune-mediated hematological disease in dogs is associated with alterations of the fecal microbiota: a pilot study.

Background: The dog is the most popular companion animal and is a valuable large animal model for several human diseases. Canine immune-mediated hematological diseases, including immune-mediated hemolytic anemia (IMHA) and immune thrombocytopenia (ITP), share many features in common with autoimmune hematological diseases of humans. The gut microbiome has been linked to systemic illness, but few studies have evaluated its association with immune-mediated hematological disease.

Does who you live with matter for your health? The influence of partners' socioeconomic characteristics on self-rated health in Norway.

Aims: Studies of the association between self-rated health and persons' income and education have almost invariably shown that people with higher education and incomes report better health. Less is known of the influence of household members' socioeconomic characteristics on individuals' health. This study thus aimed to assess the extent to which the socioeconomic characteristics of partners may contribute to explaining the variation in the respondents' self-rated health (SRH).

Intramural Purkinje fibers facilitate rapid ventricular activation in the equine heart.

Background: The Purkinje fibers convey the electrical impulses at much higher speed than the working myocardial cells. Thus, the distribution of the Purkinje network is of paramount importance for the timing and coordination of ventricular activation. The Purkinje fibers are found in the subendocardium of all species of mammals, but some mammals also possess an intramural Purkinje fiber network that provides for relatively instantaneous, burst-like activation of the entire ventricular wall, and gives rise to an rS configuration in lead II of the ECG.

Association Between Newly Diagnosed Atrial Fibrillation and Work Disability (from a Nationwide Danish Cohort Study).

It is previously shown that cardiovascular conditions have a negative effect on the ability to work. However, it is unknown if incident atrial fibrillation (AF) influences the ability to work. We examined the association between AF and the risk of work disability and the influence of socioeconomic factors.

Socioeconomic inequality in oral anticoagulation therapy initiation in patients with atrial fibrillation with high risk of stroke: a register-based observational study.

Objective: The study aimed to examine the association between socioeconomic factors (SEFs) and oral anticoagulation (OAC) therapy and whether it was influenced by changing guidelines. We hypothesised that inequities in initiation of OAC reduced over time as more detailed and explicit clinical guidelines were issued.

Design: Register-based observational study.

Antibody-mediated delivery of T-cell epitopes to antigen-presenting cells induce strong CD4 and CD8 T-cell responses.

Targeted delivery of antigen to antigen-presenting cells (APCs) enhances antigen presentation and thus, is a potent strategy for making more efficacious vaccines. This can be achieved by use of antibodies with specificity for endocytic surface molecules expressed on the APC. We aimed to compare two different antibody-antigen fusion modes in their ability to induce T-cell responses; first, exchange of immunoglobulin (Ig) constant domain loops with a T-cell epitope (Troybody), and second, fusion of T-cell epitope or whole antigen to the antibody C-terminus.

Cardiac vagal tone as a novel screening tool to recognize asymptomatic cardiovascular autonomic neuropathy: Aspects of utility in type 1 diabetes.

Aims: To test the performance of the cardiac vagal tone (CVT) derived from a 5-minute ECG recording compared with the standardized cardiovascular autonomic reflex tests (CARTs).

Methods: Cross-sectional study included 56 well-phenotyped adults with type 1 diabetes (19-71 years, 2-54 years disease-duration). Autonomic testing included: standardized CARTs obtained with the VAGUS™, CVT, and indices of heart rate variability (HRV) obtained at 24- and 120-hour, and electrochemical skin conductance assessed with SUDOSCAN®.

Patient experiences with peripherally inserted venous catheters- A cross-sectional, multicentre study in Norway.

Aim: To investigate patient experiences with peripherally inserted venous catheters, namely PICC lines and Midlines, as well as the influence of socio-demographic variables, length of stay, comorbidity and complications on these experiences.

Design: The study had a descriptive, multicentre, cross-sectional design.

Methods: We used a questionnaire to investigate patient experiences ( = 359).

Socioeconomic position and risk of atrial fibrillation: a nationwide Danish cohort study.

Aim: To examine the association between socioeconomic position and the risk of atrial fibrillation (AF) in different stages of life in a population of Danish citizens.

Methods: Register-based study. We followed all individuals turning 35, 50, 65 or 80 years from 1 January 1996 to 31 December 2005 until AF, death, emigration or the end of study period (31 December 2015).

Associations between socioeconomic status, atrial fibrillation, and outcomes: a systematic review.

Background: Atrial fibrillation (AF) is a growing epidemic and evidence of a relationship to socioeconomic status (SES) is inconsistent. We aimed to summarize the literature about SES and AF and defined two objectives: (1) To examine the association between SES and the risk of AF; (2) To examine the association between SES and AF-related outcomes in an AF-population.

Methods: We performed a separate search for each objective in Ovid-MEDLINE and Ovid-Embase.

Video-based data acquisition system for use in eye blink classical conditioning procedures in sheep.

Pavlovian eye blink conditioning (EBC) has been extensively studied in humans and laboratory animals, providing one of the best-understood models of learning in neuroscience. EBC has been especially useful in translational studies of cerebellar and hippocampal function. We recently reported a novel extension of EBC procedures for use in sheep, and now describe new advances in a digital video-based system.

Alcohol-Induced Developmental Origins of Adult-Onset Diseases.

Fetal alcohol exposure may impair growth, development, and function of multiple organ systems and is encompassed by the term fetal alcohol spectrum disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker's hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult development of chronic diseases.

Maternal and neonatal plasma microRNA biomarkers for fetal alcohol exposure in an ovine model.

Background: Plasma or circulating miRNAs (cir miRNAs) have potential diagnostic value as biomarkers for a range of diseases. Based on observations that ethanol (EtOH) altered intracellular miRNAs during development, we tested the hypothesis that plasma miRNAs were biomarkers for maternal alcohol exposure, and for past in utero exposure, in the neonate.

Methods: Pregnant sheep were exposed to a binge model of EtOH consumption resulting in an average peak blood alcohol content of 243 mg/dl, for a third-trimester-equivalent period from gestational day 4 (GD4) to GD132.

Acute alcohol exposure, acidemia or glutamine administration impacts amino acid homeostasis in ovine maternal and fetal plasma.

Fetal alcohol syndrome (FAS) is a significant problem in human reproductive medicine. Maternal alcohol administration alters maternal amino acid homeostasis and results in acidemia in both mother and fetus, causing fetal growth restriction. We hypothesized that administration of glutamine, which increases renal ammoniagenesis to regulate acid-base balance, may provide an intervention strategy.

The role of cortisol in chronic binge alcohol-induced cerebellar injury: Ovine model.

Women who drink alcohol during pregnancy are at high risk of giving birth to children with neurodevelopmental disorders. Previous reports from our laboratory have shown that third trimester equivalent binge alcohol exposure at a dose of 1.75 g/kg/day results in significant fetal cerebellar Purkinje cell loss in fetal sheep and that both maternal and fetal adrenocorticotropin (ACTH) and cortisol levels are elevated in response to alcohol treatment.

Different patterns of regional Purkinje cell loss in the cerebellar vermis as a function of the timing of prenatal ethanol exposure in an ovine model.

Studies in rat models of fetal alcohol spectrum disorders have indicated that the cerebellum is particularly vulnerable to ethanol-induced Purkinje cell loss during the third trimester-equivalent, with striking regional differences in vulnerability in which early-maturing regions in the vermis show significantly more loss than the late-maturing regions. The current study tested the hypothesis that the sheep model will show similar regional differences in fetal cerebellar Purkinje cell loss when prenatal binge ethanol exposure is restricted to the prenatal period of brain development equivalent to the third trimester and also compared the pattern of loss to that produced by exposure during the first trimester-equivalent. Pregnant Suffolk sheep were assigned to four groups: first trimester-equivalent saline control group, first trimester-equivalent ethanol group (1.

Corneal neovascularization: an anti-VEGF therapy review.

Corneal neovascularization is a serious condition that can lead to a profound decline in vision. The abnormal vessels block light, cause corneal scarring, compromise visual acuity, and may lead to inflammation and edema. Corneal neovascularization occurs when the balance between angiogenic and antiangiogenic factors is tipped toward angiogenic molecules.

CD40/APC-specific antibodies with three T-cell epitopes loaded in the constant domains induce CD4+ T-cell responses.

CD4+ T lymphocytes play a central role in the orchestration and maintenance of the adaptive immune response. Targeting of antigen to antigen presenting cells (APCs) increases peptide loading of major histocompatibility complex (MHC) class II molecules and CD4+ T-cell activation. APCs have been targeted by APC-specific recombinant antibodies (rAbs) with single T-cell epitopes integrated in the constant region of the heavy chain (C(H)).

Hemangiogenesis and lymphangiogenesis in corneal pathology.

Purpose: We characterized the presence of hemangiogenesis (HA) and lymphangiogenesis (LA) in human corneal specimens exhibiting 13 underlying pathologies.

Methods: Human corneal specimens were obtained from consenting subjects (n = 2 or n = 3 for each pathology; total sample size, n = 35). The pathological specimens were stained with hematoxylin and eosin (H&E) to determine the presence or absence of corneal neovascularization (NV) and superficial or deep stromal distribution of NV.

Stabilizing mutations increase secretion of functional soluble TCR-Ig fusion proteins.

Background: Whereas T cell receptors (TCRs) detect peptide/major histocompatibility complexes (pMHCs) with exquisite specificity, there are challenges regarding their expression and use as soluble detection molecules due to molecular instability. We have investigated strategies for the production of TCR-immunoglobulin (Ig) fusion proteins. Two different TCRs that are characteristic of a mouse model for idiotype (Id) dependent immune regulation were engineered.

Periplasmic expression of soluble single chain T cell receptors is rescued by the chaperone FkpA.

Background: Efficient expression systems exist for antibody (Ab) molecules, which allow for characterization of large numbers of individual Ab variants. In contrast, such expression systems have been lacking for soluble T cell receptors (TCRs). Attempts to generate bacterial systems have generally resulted in low yields and material which is prone to aggregation and proteolysis.

The cellular mechanism by which complementary Id+ and anti-Id antibodies communicate: T cells integrated into idiotypic regulation.

The V region antigenic determinants (idiotopes (Ids)) of antibodies (Abs) have been suggested to be involved in regulating the immune system. Certain diseases such as diabetes mellitus have recently been associated with a disequilibrium between Id(+) and anti-Id Abs. However, it is unknown how Abs carrying complementary idiotypes (that is, Id(+) and anti-Id Abs) regulate each other at the level of B and T cells.

Processing of an antigenic sequence from IgG constant domains for presentation by MHC class II.

Targeting of T cell epitopes to APC enhances T cell responses. We used an APC-specific Ab (anti-IgD) and substituted either of 18 loops connecting beta strands in human IgG constant H (C(H)) domains with a characterized T cell peptide epitope. All Ab-epitope fusion molecules were secreted from producing cells except IgG-loop 2(BC)C(H)1, and comparing levels, a hierarchy appeared with fusions involving C(H)2 > or = C(H)1 > C(H)3.

Acid-sensitive channel inhibition prevents fetal alcohol spectrum disorders cerebellar Purkinje cell loss.

Ethanol is now considered the most common human teratogen. Educational campaigns have not reduced the incidence of ethanol-mediated teratogenesis, leading to a growing interest in the development of therapeutic prevention or mitigation strategies. On the basis of the observation that maternal ethanol consumption reduces maternal and fetal pH, we hypothesized that a pH-sensitive pathway involving the TWIK-related acid-sensitive potassium channels (TASKs) is implicated in ethanol-induced injury to the fetal cerebellum, one of the most sensitive targets of prenatal ethanol exposure.

Functional phage display of two murine alpha/beta T-cell receptors is strongly dependent on fusion format, mode and periplasmic folding assistance.

Phage display has been instrumental for the success of antibody (Ab) technology. The aim of the present study was to explore phage display of soluble T-cell receptors (TCRs). A library platform that supports engineering and selection of improved TCRs to be used as detection reagents for specific antigen presentation will be very useful.