Mast Cell-Specific Expression of Human Siglec-8 in Conditional Knock-in Mice.

Sialic acid-binding Ig-like lectin 8 (Siglec-8) is expressed on the surface of human eosinophils, mast cells, and basophils-cells that participate in allergic and other diseases. Ligation of Siglec-8 by specific glycan ligands or antibodies triggers eosinophil death and inhibits mast cell degranulation; consequences that could be leveraged as treatment. However, Siglec-8 is not expressed in murine and most other species, thus limiting preclinical studies in vivo.

IL-10 signaling in dendritic cells is required for tolerance induction in a murine model of allergic airway inflammation.

Allergen specific tolerance induction efficiently ameliorates subsequent allergen induced inflammatory responses. The underlying regulatory mechanisms have been attributed mainly to interleukin (IL)-10 produced by diverse hematopoietic cells, while targets of IL-10 in allergen specific tolerance induction have not yet been well defined. Here, we investigate potential cellular targets of IL-10 in allergen specific tolerance induction using mice with a cell type specific inactivation of the IL-10 receptor gene.

Real World Lab Data: Patterns of Lymphocyte Counts in Fingolimod Treated Patients.

Objective: Fingolimod is approved for the treatment of highly active relapsing remitting multiple sclerosis (MS) patients and acts by its unique mechanism of action via sphingosine-1-phosphate receptor-modulation. Although fingolimod-associated lymphopenia is a well-known phenomenon, the exact cause for the intra- and inter-individual differences of the fluctuation of lymphocyte count and its subtypes is still subject of debate. In this analysis, we aim to estimate the significance of the individual variation of distinct lymphocyte subsets for differences in absolute lymphocyte decrease in fingolimod treated patients and discuss how different lymphocyte subset patterns are related to clinical presentation in a long-term real life setting.

Predictors of response to opicinumab in acute optic neuritis.

Objective: The objective of this study was to evaluate prespecified and post hoc analyses in RENEW subgroups to identify participants more likely to benefit from opicinumab.

Methods: RENEW assessed the efficacy/safety of opicinumab versus placebo in participants with a first unilateral acute optic neuritis (AON) episode. Difference in visual evoked potential (VEP) latency of the affected eye at 24 weeks versus the fellow eye at baseline was the primary endpoint.

Mouse mast cells and mast cell proteases do not play a significant role in acute tissue injury pain induced by formalin.

Subcutaneous formalin injections are used as a model for tissue injury-induced pain where formalin induces pain and inflammation indirectly by crosslinking proteins and directly through activation of the transient receptor potential A1 receptor on primary afferents. Activation of primary afferents leads to both central and peripheral release of neurotransmitters. Mast cells are found in close proximity to peripheral sensory nerve endings and express receptors for neurotransmitters released by the primary afferents, contributing to the neuro/immune interface.

Unimpaired Responses to Vaccination With Protein Antigen Plus Adjuvant in Mice With Kit-Independent Mast Cell Deficiency.

Innate inflammatory responses are crucial for induction and regulation of T cell and antibody responses. Mast cell (MC)-deficient mutant mice showed impaired adaptive immunity, suggesting that MCs provide essential adjuvant activities, and pharmacological MC activation was proposed as a new adjuvant principle. However, the mutations result in complex alterations of the immune system in addition to MC deficiency.

Impact of exercise intensity on oxidative stress and selected metabolic markers in young adults in Ghana.

Objective: This study aimed to evaluate the effect of different levels of exercise on markers of oxidative stress and selected metabolic parameters in Ghanaian young adults.

Results: Significant increases in a marker of oxidative stress malondialdehyde and antioxidants such as superoxide dismutase and uric acid were observed in the exercisers compared with the inactive group (p < 0.05).

Persistent presence of outer membrane epitopes during short- and long-term starvation of five Legionella pneumophila strains.

Background: Legionella pneumophila, the causative agent of Legionnaire's disease, may enter a viable but non-culturable (VBNC) state triggered by environmental stress conditions. Specific outer-membrane epitopes of L. pneumophila are used in many diagnostic applications and some of them are linked to important virulence-related factors or endotoxins.

SDVSRM - a new SSRM based technique featuring dynamically adjusted, scanner synchronized sample voltages for measurement of actively operated devices.

Scanning spreading resistance microscopy (SSRM) with its high spatial resolution and high dynamic signal range is a powerful tool for two-dimensional characterization of semiconductor dopant areas. However, the application of the method is limited to devices in equilibrium condition, as the investigation of actively operated devices would imply potential differences within the device, whereas SSRM relies on a constant voltage difference between sample surface and probe tip. Furthermore, the standard preparation includes short circuiting of all device components, limiting applications to devices in equilibrium condition.

Continuous monitoring after atrial fibrillation ablation: the LINQ AF study.

Aims: To study device performance, arrhythmia recurrence characteristics, and methods of outcome assessment using a novel implantable cardiac monitor (ICM) in patients undergoing ablation for atrial fibrillation (AF).

Methods And Results: In 419 consecutive patients undergoing first-time catheter ablation for symptomatic paroxysmal (n = 224) or persistent (n = 195) AF an ICM was injected at the end of the procedure. Telemedicine staff ensured full episode transmission coverage and manually evaluated all automatic arrhythmia episodes.

Endo-/Epicardial Catheter Ablation of Atrial Fibrillation: Feasibility, Outcome, and Insights Into Arrhythmia Mechanisms.

Background: Until today, catheter interventional mapping and ablation of atrial fibrillation (AF) has been limited to the right and left atrial endocardium. We report feasibility, electrophysiological findings, and clinical outcome using a combined endo-/epicardial catheter approach for mapping and ablation of AF.

Methods And Results: Fifty-nine patients with permanence of pulmonary vein isolation and further symptomatic recurrences of paroxysmal AF, persistent AF, or atrial tachycardia underwent reablation using biatrial endo-/epicardial mapping and ablation.

Genome-scale single-cell mechanical phenotyping reveals disease-related genes involved in mitotic rounding.

To divide, most animal cells drastically change shape and round up against extracellular confinement. Mitotic cells facilitate this process by generating intracellular pressure, which the contractile actomyosin cortex directs into shape. Here, we introduce a genome-scale microcantilever- and RNAi-based approach to phenotype the contribution of > 1000 genes to the rounding of single mitotic cells against confinement.

Calcium/Calmodulin-Dependent Protein Kinase II Activity Persists During Chronic β-Adrenoceptor Blockade in Experimental and Human Heart Failure.

Background: Considerable evidence suggests that calcium/calmodulin-dependent protein kinase II (CaMKII) overactivity plays a crucial role in the pathophysiology of heart failure (HF), a condition characterized by excessive β-adrenoceptor (β-AR) stimulation. Recent studies indicate a significant cross talk between β-AR signaling and CaMKII activation presenting CaMKII as a possible downstream mediator of detrimental β-AR signaling in HF. In this study, we investigated the effect of chronic β-AR blocker treatment on CaMKII activity in human and experimental HF.

Imaging protective mast cells in living mice during severe contact hypersensitivity.

Contact hypersensitivity (CHS) is a common skin disease induced by epicutaneous sensitization to haptens. Conflicting results have been obtained regarding pathogenic versus protective roles of mast cells (MCs) in CHS, and this has been attributed in part to the limitations of certain models for studying MC functions in vivo. Here we describe a fluorescent imaging approach that enables in vivo selective labeling and tracking of MC secretory granules by real-time intravital 2-photon microscopy in living mice, and permits the identification of such MCs as a potential source of cytokines in different disease models.

Online social support for obese adults: Exploring the role of forum activity.

Purpose: Worldwide, the number of obese persons continues to grow. Online-mediated self-help groups represent an opportunity for obese persons to support each other. The aim of our study was to evaluate whether and how the use of and active participation in online self-help groups is associated with perceived informational and emotional support among obese adults.

Antidepressant pharmacotherapy in old-age depression-a review and clinical approach.

Purpose: Depression in old age is a disabling disease associated with functional and cognitive decline severely affecting quality of life. Studies specifically investigating antidepressant treatment for this special cohort of patients remain scarce and results are often conflicting. A narrative literature review was undertaken, synthesizing findings from published studies, systematic reviews, and treatment guidelines specifically conducted in elderly depressed patients to summarize implications and current recommendations as well as gaps in evidence for old-age pharmacologic treatment.

Fingolimod additionally acts as immunomodulator focused on the innate immune system beyond its prominent effects on lymphocyte recirculation.

Background: Growing evidence emphasizes the relevance of sphingolipids for metabolism and immunity of antigen-presenting cells (APC). APCs are key players in balancing tolerogenic and encephalitogenic responses in immunology. In contrast to the well-known prominent effects of sphingosine-1-phosphate (S1P) on lymphocyte trafficking, modulatory effects on APCs have not been fully characterized.

Three-Dimensional Left Ventricular Torsion in Patients With Dilated Cardiomyopathy - A Marker of Disease Severity.

Background: LV twist has a key role in maintaining left ventricular (LV) contractility during exercise. The purpose of this study was to investigate LV torsion instead of twist as a surrogate marker of peak oxygen uptake (peak V̇O) assessed by cardiopulmonary exercise testing (CPET) in patients with non-ischemic dilated cardiomyopathy (DCM).

Methods and results: We evaluated 45 outpatients with DCM (50±12 years, 24% females) with 3D speckle-tracking electrocardiography prior to CPET.

Awareness of HIV Transmission Risks and Determinants of Sexual Behaviour: Descriptive and Multivariate Analyses among German Nursing Students.

Background And Aim: Nursing students play a crucial role in sexual health education. Evidence suggests, however, that nursing students had several gaps in their knowledge of HIV transmission. This study investigates how nursing students in Germany assess the potential risks of spreading HIV in defined situations and which factors influence the self-expressed sexual behaviour patterns of these students.

Phosphodiesterase 2 Protects Against Catecholamine-Induced Arrhythmia and Preserves Contractile Function After Myocardial Infarction.

Rationale: Phosphodiesterase 2 is a dual substrate esterase, which has the unique property to be stimulated by cGMP, but primarily hydrolyzes cAMP. Myocardial phosphodiesterase 2 is upregulated in human heart failure, but its role in the heart is unknown.

Objective: To explore the role of phosphodiesterase 2 in cardiac function, propensity to arrhythmia, and myocardial infarction.

Chronic corticosterone treatment enhances extinction-induced depression in aged rats.

Withdrawal and avoidance behavior are common symptoms of depression and can appear as a consequence of absence of reward, i.e. extinction-induced depression (EID).

Membrane-bound stem cell factor is the major but not only driver of fibroblast-induced murine skin mast cell differentiation.

The maintenance and modulation of cutaneous mast cell (MC) numbers is held to be important for skin immune responses to allergens and pathogens. The increase in MC numbers in the skin is achieved by proliferation and the differentiation of precursor to mature MCs. Fibroblast-derived SCF is thought to be the major skin MC growth factor and it potently induces MC proliferation.

Mast cells promote melanoma colonization of lungs.

Mast cells have been implicated in malignant processes, mainly through clinical correlative studies and by experiments performed using animals lacking mast cells due to defective c-kit signaling. However, mast cell-deficient mouse models based on c-kit defects have recently been questioned for their relevance. Here we addressed the effect of mast cells in a tumor setting by using transgenic Mcpt5-Cre+ R-DTA+ mice, in which the deficiency of mast cells is independent of c-kit defects.