117 research outputs found

    Parents' perception of self-advocacy of children with myositis: an anonymous online survey

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Children with complex medical issues experience barriers to the transition of care from pediatric to adult providers. We sought to identify these barriers by elucidating the experiences of patients with idiopathic inflammatory muscle disorders.</p> <p>Methods</p> <p>We collected anonymous survey data using an online website. Patients and their families were solicited from the US and Canada through established clinics for children with idiopathic inflammatory muscle diseases as well as with the aid of a nonprofit organization for the benefit of such individuals. The parents of 45 older children/young adults suffering from idiopathic inflammatory muscle diseases were surveyed. As a basis of comparison, we similarly collected data from the parents of 207 younger children with inflammatory muscle diseases. The survey assessed transition of care issues confronting families of children and young adults with chronic juvenile myositis.</p> <p>Results</p> <p>Regardless of age of the patient, respondents were unlikely to have a designated health care provider assigned to aid in transition of care and were unlikely to be aware of a posted policy concerning transition of care at their pediatrician's office. Additionally, regardless of age, patients and their families were unlikely to have a written plan for moving to adult care.</p> <p>Conclusions</p> <p>We identified deficiencies in the health care experiences of families as pertain to knowledge, self-advocacy, policy, and vocational readiness. Moreover, as children with complex medical issues grow up, parents attribute less self-advocacy to their children's level of independence.</p

    Effector CD4+ T Cell Expression Signatures and Immune-Mediated Disease Associated Genes

    Get PDF
    Genome-wide association studies (GWAS) in immune-mediated diseases have identified over 150 associated genomic loci. Many of these loci play a role in T cell responses, and regulation of T cell differentiation plays a critical role in immune-mediated diseases; however, the relationship between implicated disease loci and T cell differentiation is incompletely understood. To further address this relationship, we examined differential gene expression in naïve human CD4+ T cells, as well as in in vitro differentiated Th1, memory Th17-negative and Th17-enriched CD4+ T cells subsets using microarray and RNASeq. We observed a marked enrichment for increased expression in memory CD4+ compared to naïve CD4+ T cells of genes contained among immune–mediated disease loci. Within memory T cells, expression of disease-associated genes was typically increased in Th17-enriched compared to Th17-negative cells. Utilizing RNASeq and promoter methylation studies, we identified a differential regulation pattern for genes solely expressed in Th17 cells (IL17A and CCL20) compared to genes expressed in both Th17 and Th1 cells (IL23R and IL12RB2), where high levels of promoter methylation are correlated to near zero RNASeq levels for IL17A and CCL20. These findings have implications for human Th17 celI plasticity and for the regulation of Th17-Th1 expression signatures. Importantly, utilizing RNASeq we found an abundant isoform of IL23R terminating before the transmembrane domain that was enriched in Th17 cells. In addition to molecular resolution, we find that RNASeq provides significantly improved power to define differential gene expression and identify alternative gene variants relative to microarray analysis. The comprehensive integration of differential gene expression between cell subsets with disease-association signals, and functional pathways provides insight into disease pathogenesis

    Brugia malayi Antigen (BmA) inhibits HIV-1 trans-infection but neither BmA nor ES-62 alter HIV-1 infectivity of DC induced CD4+ Th-cells

    Get PDF
    One of the hallmarks of HIV-1 disease is the association of heightened CD4+ T-cell activation with HIV-1 replication. Parasitic helminths including filarial nematodes have evolved numerous and complex mechanisms to skew, dampen and evade human immune responses suggesting that HIV-1 infection may be modulated in co-infected individuals. Here we studied the effects of two filarial nematode products, adult worm antigen from Brugia malayi (BmA) and excretory-secretory product 62 (ES-62) from Acanthocheilonema viteae on HIV-1 infection in vitro. Neither BmA nor ES-62 influenced HIV-1 replication in CD4+ enriched T-cells, with either a CCR5- or CXCR4-using virus. BmA, but not ES-62, had the capacity to bind the C-type lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) thereby inhibiting HIV-1 trans-infection of CD4+ enriched T-cells. As for their effect on DCs, neither BmA nor ES-62 could enhance or inhibit DC maturation as determined by CD83, CD86 and HLA-DR expression, or the production of IL-6, IL-10, IL-12 and TNF-α. As expected, due to the unaltered DC phenotype, no differences were found in CD4+ T helper (Th) cell phenotypes induced by DCs treated with either BmA or ES-62. Moreover, the HIV-1 susceptibility of the Th-cell populations induced by BmA or ES-62 exposed DCs was unaffected for both CCR5- and CXCR4-using HIV-1 viruses. In conclusion, although BmA has the potential capacity to interfere with HIV-1 transmission or initial viral dissemination through preventing the virus from interacting with DCs, no differences in the Th-cell polarizing capacity of DCs exposed to BmA or ES-62 were observed. Neither antigenic source demonstrated beneficial or detrimental effects on the HIV-1 susceptibility of CD4+ Th-cells induced by exposed DCs

    Problem Behavior in Children of Chronically Ill Parents: A Meta-Analysis

    Get PDF
    The aim of this meta-analysis is to examine whether children of chronically ill parents differ from norm groups in problem behavior. We report moderator effects and overall effect sizes for internalizing, externalizing and total problem behavior assessed by children and parents. In fixed effect models, we found a significant overall effect size for internalizing problem behavior (number of studies k = 19, total sample size N = 1,858, Cohen’s d = .23, p < .01) and externalizing problem behavior (k = 13, N = 1,525, d = .09, p < .01) but not for total problem behavior (k = 7; N = 896). Effects for internalizing and externalizing problem behavior were larger in non-cancer studies, in samples including younger children and younger ill parents, in samples defined by low average SES and in studies including parents with longer illness duration. In addition, effects for externalizing problem behavior were larger in studies characterized by a higher percentage of ill mothers and single parents. With exclusive self-report, effect sizes were significant for all problem behaviors. Based on these results, a family-centered approach in health care is recommended

    Modification of the FoxP3 Transcription Factor Principally Affects Inducible T Regulatory Cells in a Model of Experimental Autoimmune Encephalomyelitis

    Get PDF
    T regulatory (Treg) cells expressing the transcription factor FoxP3 play a key role in protection against autoimmune disease. GFP-FoxP3 reporter mice have been used widely to study the induction, function and stability of both thymically- and peripherally-induced Treg cells. The N-terminal modification of FoxP3, however, affects its interaction with transcriptional co-factors; this can alter Treg cell development and function in certain self-antigen specific animal models. Interestingly, Treg cell function can be negatively or positively affected, depending on the nature of the model. In this study, we focused on the effect of the GFP-FoxP3 reporter on Treg cell development and function in the Tg4 mouse model. In this model, T cells express a transgenic T cell receptor (TCR) specific for the Myelin Basic Protein (MBP) peptide Ac1-9, making the animals susceptible to experimental autoimmune encephalomyelitis (EAE), a disease akin to multiple sclerosis in humans. Unlike diabetes-susceptible mice, Tg4 FoxP3(gfp) mice did not develop spontaneous autoimmune disease and did not demonstrate augmented susceptibility to induced disease. Concurrently, thymic generation of natural Treg cells was not negatively affected. The induction of FoxP3 expression in naive peripheral T cells was, however, significantly impaired as a result of the transgene. This study shows that the requirements for the interaction of FoxP3 with co-factors, which governs its regulatory ability, differ not only between natural and inducible Treg cells but also between animal models of diseases such as diabetes and EAE

    Role of high tibial osteotomy in chronic injuries of posterior cruciate ligament and posterolateral corner

    Get PDF
    High tibial osteotomy (HTO) is a surgical procedure used to change the mechanical weight-bearing axis and alter the loads carried through the knee. Conventional indications for HTO are medial compartment osteoarthritis and varus malalignment of the knee causing pain and dysfunction. Traditionally, knee instability associated with varus thrust has been considered a contraindication. However, today the indications include patients with chronic ligament deficiencies and malalignment, because an HTO procedure can change not only the coronal but also the sagittal plane of the knee. The sagittal plane has generally been ignored in HTO literature, but its modification has a significant impact on biomechanics and joint stability. Indeed, decreased posterior tibial slope causes posterior tibia translation and helps the anterior cruciate ligament (ACL)-deficient knee. Vice versa, increased tibial slope causes anterior tibia translation and helps the posterior cruciate ligament (PCL)-deficient knee. A review of literature shows that soft tissue procedures alone are often unsatisfactory for chronic posterior instability if alignment is not corrected. Since limb alignment is the most important factor to consider in lower limb reconstructive surgery, diagnosis and treatment of limb malalignment should not be ignored in management of chronic ligamentous instabilities. This paper reviews the effects of chronic posterior instability and tibial slope alteration on knee and soft tissues, in addition to planning and surgical technique for chronic posterior and posterolateral instability with HTO

    Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

    Get PDF
    The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers

    Mechanisms of T cell organotropism

    Get PDF
    F.M.M.-B. is supported by the British Heart Foundation, the Medical Research Council of the UK and the Gates Foundation
    corecore