Toll-like receptor signaling in the establishment and function of the immune system

Toll-like receptors (TLRs) are pattern recognition receptors that play a central role in the development and function of the immune system. TLR signaling promotes the earliest emergence of hematopoietic cells during development, and thereafter influences the fate and function of both primitive and effector immune cell types. Aberrant TLR signaling is associated with hematopoietic and immune system dysfunction, and both loss- and gain-of- function variants in TLR signaling-associated genes have been linked to specific infection susceptibilities and immune defects. Herein, we will review the role of TLR signaling in immune system development and the growing number of heritable defects in TLR signaling that lead to inborn errors of immunity

Social Identity, Self-Esteem, and Mental Health in Autism

We investigated Autism social identity and mental health in autistic people. Autistic people have social and communication deficits, and experience social stigma—factors that could interfere with the development of positive social identity. Indeed, autistic participants (N = 272) had significantly lower personal self-esteem, and higher levels of depression and anxiety than typically developing controls (N = 267). Autism social identification was positively associated with personal self-esteem, and this relationship was mediated by collective self-esteem (perceived positivity of Autism identity). Furthermore, there were significant negative indirect effects between Autism identification and anxiety, and between Autism identification and depression, through increases in collective self-esteem and personal self-esteem. Thus, while autistic participants reported poorer mental health than average, having a positive Autism social identity appeared to offer a protective mechanism. This implies that to improve mental health in the Autism population, clinical approaches should aim to facilitate development of positive Autism identities.<br/

Humoral immune response of pregnant goats to two Corynebacterium pseudotuberculosis bacterin formulations

Caseous lymphadenitis is a chronic suppurative bacterial disease caused by Corynebacterium pseudotuberculosis, and it has a high prevalence among small ruminants. Different vaccine preparations have been employed to control this disease. The adjuvant used in the formulation is a critical factor for the improvement of vaccine efficacy. No commercial vaccines are available in Argentina. The aims of the present work were to compare the specific antibody response against a C. pseudotuberculosis whole cell vaccine formulated with a classical and an immunoestimulant adjuvant in pregnant goats, and to assess the transfer of vaccine-specific antibodies from the goat to the offspring through colostrum. Twenty three pregnant goats were vaccinated. The animals were randomly allocated to three groups: control, aluminum hydroxide Al(OH)3 adjuvant and a new cage-like particle adjuvant (ISPA). Antibodies (IgG) against this antigen were measured by ELISA. A robust humoral immune response was detected in vaccinated animals, with production of specific IgG. No significant differences were found between the vaccines formulated with different adjuvants. High levels of specific antibodies were detected in colostrum samples from both immunised groups, which were passively transferred from goats to offprings. No adverse local reactions in the vaccines injection sites were detected

Migration and allergic diseases in a rural area of a developing country.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-02-10T17:02:09Z No. of bitstreams: 1 Rodriguez A Migration and allergic....pdf: 149809 bytes, checksum: dd2e77d239dd95d5fbf01198a195d13a (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-02-10T17:40:30Z (GMT) No. of bitstreams: 1 Rodriguez A Migration and allergic....pdf: 149809 bytes, checksum: dd2e77d239dd95d5fbf01198a195d13a (MD5)Made available in DSpace on 2017-02-10T17:40:30Z (GMT). No. of bitstreams: 1 Rodriguez A Migration and allergic....pdf: 149809 bytes, checksum: dd2e77d239dd95d5fbf01198a195d13a (MD5) Previous issue date: 2016Wellcome Trust (grant nos. 072405/Z/03/Z and 088862/Z/09/Z).Laboratorio de Investigaci on FEPIS. Quinind e, Esmeraldas Province, Ecuador / Faculty of Epidemiology and Population Health. London School of Hygiene and Tropical Medicine. London, United Kingdom / Universidad Internacional del Ecuador. Facultad de Ciencias Medicas de la Salud y la Vida. Quito, EcuadorLaboratorio de Investigaci on FEPIS. Quinind e, Esmeraldas Province, EcuadorLaboratorio de Investigaci on FEPIS. Quinind e, Esmeraldas Province, EcuadorFaculty of Epidemiology and Population Health. London School of Hygiene and Tropical Medicine. London, United KingdomFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Instituto de Saúde Coletiva. Salvador, BA, BrasilLaboratorio de Investigaci on FEPIS. Quinind e, Esmeraldas Province, Ecuador / Universidad Internacional del Ecuador. Facultad de Ciencias Medicas de la Salud y la Vida. Quito, Ecuador / St George’s University of London. Institute of Infection and Immunity. London, United Kingdo

A Quantum Mechanical Model of Spherical Supermembranes

We present a quantum mechanical model of spherical supermembranes. Using superfields to represent the cartesian coordinates of the membrane, we are able to exactly determine its supersymmetric vacua. We find there are two classical vacua, one corresponding to an extended membrane and one corresponding to a point-like membrane. For the ${\mathcal N} = 2$ case, instanton effects then lift these vacua to massive states. For the ${\mathcal N} = 4$ case, there is no instanton tunneling, and the vacua remain massless. Similarities to spherical supermembranes as giant gravitons and in Matrix theory on pp-waves is discussed.Comment: 9 page

Design of the Subpopulations and Intermediate Outcome Measures in COPD (SPIROMICS) AIR Study.

IntroductionPopulation-based epidemiological evidence suggests that exposure to ambient air pollutants increases hospitalisations and mortality from chronic obstructive pulmonary disease (COPD), but less is known about the impact of exposure to air pollutants on patient-reported outcomes, morbidity and progression of COPD.Methods and analysisThe Subpopulations and Intermediate Outcome Measures in COPD (SPIROMICS) Air Pollution Study (SPIROMICS AIR) was initiated in 2013 to investigate the relation between individual-level estimates of short-term and long-term air pollution exposures, day-to-day symptom variability and disease progression in individuals with COPD. SPIROMICS AIR builds on a multicentre study of smokers with COPD, supplementing it with state-of-the-art air pollution exposure assessments of fine particulate matter, oxides of nitrogen, ozone, sulfur dioxide and black carbon. In the parent study, approximately 3000 smokers with and without airflow obstruction are being followed for up to 3 years for the identification of intermediate biomarkers which predict disease progression. Subcohorts undergo daily symptom monitoring using comprehensive daily diaries. The air monitoring and modelling methods employed in SPIROMICS AIR will provide estimates of individual exposure that incorporate residence-specific infiltration characteristics and participant-specific time-activity patterns. The overarching study aim is to understand the health effects of short-term and long-term exposures to air pollution on COPD morbidity, including exacerbation risk, patient-reported outcomes and disease progression.Ethics and disseminationThe institutional review boards of all the participating institutions approved the study protocols. The results of the trial will be presented at national and international meetings and published in peer-reviewed journals

Eficacia reducida de derquantel y abamectina en ovinos y caprinos con Haemonchus sp resistentes a lactonas macrocíclicas

Se presentan las observaciones efectuadas sobre la actividad de una combinación antihelmíntica conteniendo un nueva droga, el derquantel (spiroindoles) adicionada con abamectina (lactonas macrocíclicas) en ovinos y caprinos naturalmente parasitados por Haemonchus sp. En el conteo de huevos, la eficacia de la combinación mostró porcentajes de reducción variables y dependientes de los estadios parasitarios intervinientes al momento del tratamiento y al status previo de resistencia a las lactonas macrocíclicas. Se observó una eficacia alta (mayor al 99%) frente a la oviposición de estadios maduros de Haemonchus sp o cuando los antecedentes de las poblaciones parasitarias indicaban resistencia no marcada a las lactonas macrocíclicas. Por el contrario, eficacias inferiores (76 al 83%) se observaron cuando las poblaciones de este parásito mostraban resistencia severa a las lactonas macrocíclicas y los estadios inmaduros constituían la mayor parte de la población parasitaria al momento del tratamiento. Las combinaciones antihelmínticas tienen un interesante potencial de uso frente a poblaciones parasitarias de Haemonchus sp resistentes a los antihelmínticos, pero las presentes observaciones enfatizan la necesidad de evaluar a nivel de cada establecimiento la actividad de todos los antiparasitarios, sean estos formulados con viejas o nuevas drogas, si se pretende instaurar programas racionales para el control de estos nematodesA field study was carried out to determine the activity of an anthelmintic combination of derquantel (spiroindoles) plus abamectin (macrocyclic lactones) against Haemonchus sp in sheeps and goats. The clinical efficacy of the combination showed variable egg count reduction percentage dependent on the parasitic stages involved at the time of treatment and the previous status of resistance to the macrocyclic lactones. High efficacy (greater than 99%) was observed against oviposition of mature Haemonchus sp stages or when background of parasitic populations indicated moderate resistance to macrocyclic lactones. In contrast, lower efficiencies (76-83%) were observed when populations of this parasite showed severe resistance to macrocyclic lactones and immature stages constituted the majority of the parasitic population at time of treatment. Anthelmintic combinations could have an interesting potential for prevent o manage the nematode resistance in small ruminants, but the present observations emphasize the need to evaluate at the level of each establishment the activity of all anthelmintic drenches formulated with new or old drugsEEA RafaelaFil: Cerutti, Julieta. Universidad Católica de Córdoba. Facultad Ciencias Agropecuarias; ArgentinaFil: Cooper, Laura G. Universidad Católica de Córdoba. Facultad Ciencias Agropecuarias; ArgentinaFil: Torrents, Jorgelina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Suarez Archilla, Guillermo Alejandro. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Anziani, Oscar Sergio. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; Argentina. Universidad Católica de Córdoba. Facultad de Ciencias Agropecuarias, Argentin

Codon-precise, synthetic, antibody fragment libraries built using automated hexamer codon additions and validated through next generation sequencing

We have previously described ProxiMAX, a technology that enables the fabrication of precise, combinatorial gene libraries via codon-by-codon saturation mutagenesis. ProxiMAX was originally performed using manual, enzymatic transfer of codons via blunt-end ligation. Here we present Colibra™: an automated, proprietary version of ProxiMAX used specifically for antibody library generation, in which double-codon hexamers are transferred during the saturation cycling process. The reduction in process complexity, resulting library quality and an unprecedented saturation of up to 24 contiguous codons are described. Utility of the method is demonstrated via fabrication of complementarity determining regions (CDR) in antibody fragment libraries and next generation sequencing (NGS) analysis of their quality and diversity

The electronic medication complete communication (EMC2) study: Rationale and methods for a randomized controlled trial of a strategy to promote medication safety in ambulatory care

AbstractBackgroundAdverse drug events (ADEs) affect millions of patients annually and place a significant burden on the healthcare system. The Food and Drug Administration (FDA) has developed patient safety information for high-risk medications that pose serious public health concerns. However, there are currently few assurances that patients receive this information or are able to identify or respond correctly to ADEs.ObjectiveTo evaluate the effectiveness of the Electronic Medication Complete Communication (EMC2) Strategy to promote safe medication use and reporting of ADEs in comparison to usual care.MethodsThe automated EMC2 Strategy consists of: 1) provider alerts to counsel patients on medication risks, 2) the delivery of patient-friendly medication information via the electronic health record, and 3) an automated telephone assessment to identify potential medication concerns or ADEs. The study will take place in two community health centers in Chicago, IL. Adult, English or Spanish-speaking patients (N=1200) who have been prescribed a high-risk medication will be enrolled and randomized to the intervention arm or usual care based upon practice location. The primary outcomes of the study are medication knowledge, proper medication use, and reporting of ADEs; these will be measured at baseline, 4weeks, and three months. Intervention fidelity as well as barriers and costs of implementation will be evaluated.ConclusionsThe EMC2 Strategy automates a patient-friendly risk communication and surveillance process to promote safe medication use while minimizing clinic burden. This trial seeks to evaluate the effectiveness and feasibility of this strategy in comparison to usual care