Cellular and Molecular Mechanisms of Pain

The nervous system detects and interprets a wide range of thermal and mechanical stimuli, as well as environmental and endogenous chemical irritants. When intense, these stimuli generate acute pain, and in the setting of persistent injury, both peripheral and central nervous system components of the pain transmission pathway exhibit tremendous plasticity, enhancing pain signals and producing hypersensitivity. When plasticity facilitates protective reflexes, it can be beneficial, but when the changes persist, a chronic pain condition may result. Genetic, electrophysiological, and pharmacological studies are elucidating the molecular mechanisms that underlie detection, coding, and modulation of noxious stimuli that generate pain

Neutrophils promote CXCR3-dependent itch in the development of atopic dermatitis.

Chronic itch remains a highly prevalent disorder with limited treatment options. Most chronic itch diseases are thought to be driven by both the nervous and immune systems, but the fundamental molecular and cellular interactions that trigger the development of itch and the acute-to-chronic itch transition remain unknown. Here, we show that skin-infiltrating neutrophils are key initiators of itch in atopic dermatitis, the most prevalent chronic itch disorder. Neutrophil depletion significantly attenuated itch-evoked scratching in a mouse model of atopic dermatitis. Neutrophils were also required for several key hallmarks of chronic itch, including skin hyperinnervation, enhanced expression of itch signaling molecules, and upregulation of inflammatory cytokines, activity-induced genes, and markers of neuropathic itch. Finally, we demonstrate that neutrophils are required for induction of CXCL10, a ligand of the CXCR3 receptor that promotes itch via activation of sensory neurons, and we find that that CXCR3 antagonism attenuates chronic itch

The Epithelial Cell-Derived Atopic Dermatitis Cytokine TSLP Activates Neurons to Induce Itch

SummaryAtopic dermatitis (AD) is a chronic itch and inflammatory disorder of the skin that affects one in ten people. Patients suffering from severe AD eventually progress to develop asthma and allergic rhinitis, in a process known as the “atopic march.” Signaling between epithelial cells and innate immune cells via the cytokine thymic stromal lymphopoietin (TSLP) is thought to drive AD and the atopic march. Here, we report that epithelial cells directly communicate to cutaneous sensory neurons via TSLP to promote itch. We identify the ORAI1/NFAT calcium signaling pathway as an essential regulator of TSLP release from keratinocytes, the primary epithelial cells of the skin. TSLP then acts directly on a subset of TRPA1-positive sensory neurons to trigger robust itch behaviors. Our results support a model whereby calcium-dependent TSLP release by keratinocytes activates both primary afferent neurons and immune cells to promote inflammatory responses in the skin and airways

Higher levels of secretory IgA are associated with low disease activity index in patients with reactive arthritis and undifferentiated spondyloarthritis

Introduction: Both reactive arthritis (ReA) and undifferentiated spondyloarthritis (uSpA) belong to the group of autoinflammatory diseases called spondyloarthritis (SpA). Hypotheses have been proposed about a relationship between the intestinal mucosa and inflammation of joint tissues. The role of immunoglobulin IgA or secretory immunoglobulin A (SIgA) in the inflammatory and/or clinical activity of patients with SpA remains poorly understood. Objective: To evaluate the status of total IgA and SIgA, and the association among the levels of SIgA, IgA, IgA anti-Chlamydia trachomatis, and anti-Shigella spp. with the disease activity measures, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, was compared in a cohort of patients with ReA and uSpA and healthy subjects. Methods: This was a cross-sectional study. The serum concentrations of SIgA, IgA anti-C. trachomatis, anti-Shigella spp., and total IgA were measured. Disease activity was measured in each patient by means of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS). Statistical analysis did include as bivariate evaluation, comparisons by Student’s t-test, Kruskal–Wallis test, and U Mann–Whitney test, with a multivariate evaluation by principal components analysis (PCA). A correlation analysis was carried out using the Pearson correlation coefficient and a linear regression models. All analysis were made using Stata version 11.2® for Windows, R V3.3.21. Statistical significance was defined a p-value <0.05. Results: In all, 46 patients (78.2% men; mean age, 34.8 ± 12.3 years) and 53 controls (41% men; mean age, 32 ± 11.4 years) were included in the study. The mean serum levels of SIgA were higher in SpA patients than in healthy subjects (p < 0.001). Only SIgA levels correlated with disease activity: BASDAI (r = −0.42, p = 0.0046), ASDAS-CRP (r = −0.37, p = 0.014), and ASDAS-ESR (r = −0.45, p = 0.0021). The negative correlation between SIgA and all activity indices was higher in HLA-B27-positive patients (BASDAI r = −0.70, p = 0.0009, ASDAS-CRP r = −0.58, p = 0.0093, and ASDAS-ESR r = −0.57, p = 0.0083). The PCA showed three factors: the first component was constituted by variables referred as clinical activity measures, the second did include the serological activity markers, and the last component was compounded by age and symptoms time. Conclusion: Elevated serum levels of SIgA were found to be related with low disease activity in patients with ReA and uSpA

Propuesta de Supply Chain Management y Logística para la empresa Bimbo Colombia S.A.S.

Pertenecemos al Grupo 15 del curso Diplomado de profundización en Supply Chain Management y Logística O.G 207115A-955; durante todo el proceso de diplomado hemos estudiado 10 unidades con diferentes temas y actividades en la cual completamos la planificación del sistema SCM y en este documento lo que hacemos es una compilación de todo el material que resultó de cada unidad; para la realización del diplomado debimos escoger una empresa sujeta de la planificación y en conjunto tomamos la decisión de que fuera la empresa Bimbo SAS ya que es una multinacional presente en tres continentes y muchos países con diferentes esquemas de logística (ver www.grupobimbo.com), lo cual nos permitía abarcar todos los temas de estudioWe belong to Group 15 of the Diploma course in Supply Chain Management and Logistics OG 207115A-955; Throughout the diploma process we have studied 10 units with different topics and activities in which we complete the planning of the SCM system and in this document what we do is a compilation of all the material that resulted from each unit; To carry out the diploma course, we had to choose a company subject to planning and together we made the decision that it be the Bimbo SAS company, since it is a multinational present on three continents and in many countries with different logistics schemes (see www.grupobimbo.com ), which allowed us to cover all the study topic

Quantum logic inspired techniques for spacetime-symmetry tests with (anti-)protons

Cosmological observations as well as theoretical approaches to physics beyond the standard model provide strong motivations for experimental tests of fundamental symmetries, such as CPT invariance. In this context, the availability of cold baryonic antimatter at CERN has opened an avenue for ultrahigh-precision comparisons of protons and antiprotons in Penning traps. This work discusses an experimental method inspired by quantum logic techniques that will improve particle localization and readout speed in such experiments. The method allows for sympathetic cooling of the (anti-)proton to its quantum-mechanical ground state as well as the readout of its spin alignment, replacing the commonly used continuous Stern–Gerlach effect. Both of these features are achieved through coupling to a laser-cooled 'logic' ion co-trapped in a double-well potential. This technique will boost the measurement sampling rate and will thus provide results with lower statistical uncertainty, contributing to stringent searches for time dependent variations in the data. Such measurements ultimately yield extremely high sensitivities to CPT violating coefficients acting on baryons in the standard-model extension, will allow the exploration of previously unmeasured types of symmetry violations, and will enable antimatter-based axion-like dark matter searches with improved mass resolution

Seroprevalence of bovine viral diarrhea virus (BVDV) in cattle from Sotaquirá, Colombia

Worldwide distributed Bovine Viral Diarrhea Virus (BVDV) represents a high risk of infection in most bovine farms, in which it is associated with gastrointestinal, respiratory, and reproductive diseases. The purpose of this research was to establish the seroprevalence and the main risk factors associated with the presentation of BVDV in the municipality of Sotaquirá, Colombia. Samples were taken from 1000 cattle of Holstein, Ayrshire, Jersey, Normande Gyr and Holstein x Gyr. Epidemiological surveys were implemented, reproductive and management variables were taken into consideration. Indirect ELISA was performed to detect specific antibodies against BVDV using the commercial kit SERELISA® BVD p80 Ab Mono Blocking. The overall seroprevalence of antibodies against BVDV was 42.5% (425/1000), where the Gyr breed (59.1% apparent prevalence (AP); 60.3% real prevalence (PR)) and the age group > 4 years (53.0% PA; 54.4% PR) presented the highest seroprevalences. A significant statistical association was found for the breed, age, management practices evaluated and the presentation of PI3 (p ≤ 0.05). Age group > 4 years, Normande breed, presentation of PI3 and grazing lease were established as risk factors associated with BVDV in the herds. These infections are mainly associated with dairy cattle and herds with many animals, so it is important to consider vaccination plans as a preventive system and follow up on the most common diseases