Immunopathology of CD4+ T Cell-Mediated Autoimmune Responses to Central Nervous System Antigens: Role of IL-16

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating and degenerative disease of the central nervous system (CNS). While etiology of the disease remains unknown, genetic susceptibility and autoimmune mechanisms in the initiation and progression of the disease have been strongly suggested. Experimental autoimmune encephalomyelitis (EAE) is commonly used to study immune regulation of MS. Infiltration by CD4+ T cells, through blood-brain barrier (BBB), precedes the onset and relapses of MS. CNS migration and homing patterns of T cells are tightly synchronized by astrocyte and microglia derived cytokines and chemokines. Autoimmune, CNS antigenreactive, infiltrating T cells produce and locally release cytokines including but not limited to IFNγ, IL-2, IL-6, IL-16, IL-17, TNFα, and chemokines including CCL2, CCL5 and CXCL10. Chemokine mediated chemotaxis is exclusive for activated cell state and most chemokines do not discriminate between distinct cell types. Conversely, a cytokine IL-16 is a CD4-specific cytokine-ligand and exclusively induces chemotaxis of CD4+T cells, by binding and signaling through CD4, regardless of T cell activation state. In this article we focus on CD4+ T cell-mediated autoimmune responses to CNS antigens because of their importance for immunopathology of MS and EAE. We focus on autoimmune responses to myelin oligodendrocyte glycoprotein (MOG) because of its relevance for immunopathology of MS. We emphasize a role of IL-16 in regulation of CD4+T cell mediated autoimmune responses to MOG in EAE and MS. While a role of IL-16 in regulation of other CD4+T cell mediated autoimmune diseases has been established, its role in regulation of MS remains to be determined. Emerging data from our laboratories have indicated that IL-16-mediated CD4+ T cell chemoattraction has a significant role in regulation of CD4+ T cell-mediated autoimmune responses to CNS antigens. We propose an important function of this cytokine in regulation of relapsing-remitting EAE

Damping device for a stationary labyrinth seal

A stationary labyrinth seal system includes a seal housing having an annular cavity, a plurality of damping devices, and a retaining ring. The damping devices are positioned within the annular cavity and are maintained within the annular cavity by the retaining ring

Patient characteristics associated with treatment initiation among paediatric patients with Attention-Deficit/Hyperactivity Disorder symptoms in a naturalistic setting in Central Europe and East Asia

BACKGROUND: Cultural views of Attention-Deficit/Hyperactivity Disorder (ADHD), differing healthcare systems and funding mechanisms, and the availability of mental health services can greatly influence the perceptions, diagnosis, and treatment of ADHD. There is, however, lack of information about treatment practice and the treatment decision-making process for ADHD, particularly in non-Western countries. Our study compared characteristics of paediatric patients newly diagnosed with ADHD symptoms who did and who did not initiate treatment, and also examined whether any differences varied by region in Central Europe and East Asia. METHODS: Data were taken from a 1-year prospective, observational study that included 1,068 paediatric patients newly diagnosed with ADHD symptoms. Clinical severity was measured using the Clinical Global Impression-ADHD-Severity (CGI-ADHD-S) scale and the Child Symptom Inventory-4 (CSI-4) checklist. Logistic regression was used to explore patient characteristics associated with treatment initiation (pharmacotherapy and/or psychotherapy) at baseline for each region. RESULTS: A total of 74.3% of patients initiated treatment at baseline (78.3% in Central Europe and 69.9% in East Asia). Of these, 48.8% started with both pharmacotherapy and psychotherapy in Central Europe, and only 17.1% did so in East Asia. The level of clinical severity was highest in the combination treatment group in Central Europe, but was highest in the psychotherapy only group in East Asia. In East Asia, treatment initiation was associated with being older, being male, and having a higher CGI-ADHD-S score. In Central Europe, treatment initiation was associated with parental psychological distress, having a higher CSI-4 score, and not being involved in bullying. CONCLUSIONS: Although factors associated with treatment initiation differed to some extent between Central Europe and East Asia, clinical severity appeared to be one of the most important determinants of treatment initiation in both regions. However, the choice between pharmacotherapy and psychotherapy, either alone or in combination, varied substantially across the regions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12888-014-0304-x) contains supplementary material, which is available to authorized users

Predictors and consequences of adherence to the treatment of pediatric patients with attention-deficit/hyperactivity disorder in Central Europe and East Asia.

PURPOSE: To assess baseline predictors and consequences of medication non-adherence in the treatment of pediatric patients with attention-deficit/hyperactivity disorder (ADHD) from Central Europe and East Asia. PATIENTS AND METHODS: Data for this post-hoc analysis were taken from a 1-year prospective, observational study that included a total of 1,068 newly-diagnosed pediatric patients with ADHD symptoms from Central Europe and East Asia. Medication adherence during the week prior to each visit was assessed by treating physicians using a 5-point Likert scale, and then dichotomized into either adherent or non-adherent. Clinical severity was measured by the Clinical Global Impressions-ADHD-Severity (CGI-ADHD) scale and the Child Symptom Inventory-4 (CSI-4) Checklist. Health-Related Quality of Life (HRQoL) was measured using the Child Health and Illness Profile-Child Edition (CHIP-CE). Regression analyses were used to assess baseline predictors of overall adherence during follow-up, and the impact of time-varying adherence on subsequent outcomes: response (defined as a decrease of at least 1 point in CGI), changes in CGI-ADHD, CSI-4, and the five dimensions of CHIP-CE. RESULTS: Of the 860 patients analyzed, 64.5% (71.6% in Central Europe and 55.5% in East Asia) were rated as adherent and 35.5% as non-adherent during follow-up. Being from East Asia was found to be a strong predictor of non-adherence. In East Asia, a family history of ADHD and parental emotional distress were associated with non-adherence, while having no other children living at home was associated with non-adherence in Central Europe as well as in the overall sample. Non-adherence was associated with poorer response and less improvement on CGI-ADHD and CSI-4, but not on CHIP-CE. CONCLUSION: Non-adherence to medication is common in the treatment of ADHD, particularly in East Asia. Non-adherence was associated with poorer response and less improvement in clinical severity. A limitation of this study is that medication adherence was assessed by the treating clinician using a single item question

Patient characteristics associated with treatment initiation among paediatric patients with Attention-Deficit/Hyperactivity Disorder symptoms in a naturalistic setting in Central Europe and East Asia.

BACKGROUND: Cultural views of Attention-Deficit/Hyperactivity Disorder (ADHD), differing healthcare systems and funding mechanisms, and the availability of mental health services can greatly influence the perceptions, diagnosis, and treatment of ADHD. There is, however, lack of information about treatment practice and the treatment decision-making process for ADHD, particularly in non-Western countries. Our study compared characteristics of paediatric patients newly diagnosed with ADHD symptoms who did and who did not initiate treatment, and also examined whether any differences varied by region in Central Europe and East Asia. METHODS: Data were taken from a 1-year prospective, observational study that included 1,068 paediatric patients newly diagnosed with ADHD symptoms. Clinical severity was measured using the Clinical Global Impression-ADHD-Severity (CGI-ADHD-S) scale and the Child Symptom Inventory-4 (CSI-4) checklist. Logistic regression was used to explore patient characteristics associated with treatment initiation (pharmacotherapy and/or psychotherapy) at baseline for each region. RESULTS: A total of 74.3% of patients initiated treatment at baseline (78.3% in Central Europe and 69.9% in East Asia). Of these, 48.8% started with both pharmacotherapy and psychotherapy in Central Europe, and only 17.1% did so in East Asia. The level of clinical severity was highest in the combination treatment group in Central Europe, but was highest in the psychotherapy only group in East Asia. In East Asia, treatment initiation was associated with being older, being male, and having a higher CGI-ADHD-S score. In Central Europe, treatment initiation was associated with parental psychological distress, having a higher CSI-4 score, and not being involved in bullying. CONCLUSIONS: Although factors associated with treatment initiation differed to some extent between Central Europe and East Asia, clinical severity appeared to be one of the most important determinants of treatment initiation in both regions. However, the choice between pharmacotherapy and psychotherapy, either alone or in combination, varied substantially across the regions

Ways of coping and behavior in adolescent resilient spectator violence among peers

Se examina la relación entre los modos de afrontamiento y la conducta resiliente en adolescentes espectadores de violencia entre pares en ambientes educativos. Se indaga si los tipos de espectadores reconocidos por la literatura especializada (indiferente, culpabilizado, amoral y prosocial) se diferencian en cuanto a los modos de afrontamiento al estrés en este tipo de situaciones, y si, en promedio, se diferencian en cuanto al grado de resiliencia que manifiestan. Para ello se evaluó una muestra representativa con la Escala de Resiliencia, el Cuestionario de Modos de Afrontamiento y una Escala de Tipo de Espectador de Violencia Entre Pares (TEVP), elaborada por los responsables del estudio. Los datos indican que existen diferencias significativas en ciertos modos de afrontamiento, en la conducta resiliente, y entre ésta y la mayoría de los modos de afrontamiento manifestados por los distintos tipos de espectadores de violencia entre pares. Asimismo, se corrobora que la escala TEVP, elaborada para el presente estudio, es válida y confiable. === === ABSTRACT === === Examines the relationship between ways of coping and resilience behavior in adolescent spectators peer violence in educational environments. Inquires whether the types of viewers recognized by the literature (indifferent, guilty, amoral and prosocial), they differ on the coping modes with stress dealing with these situations, and if, on average, differ in terms of degree of resilience that they reveal. This evaluated a representative sample of the Resilience Scale, the Ways of Coping Questionnaire and a Scale Type Spectator Peer violence (TSPV) developed by those responsible for the study. The data indicate that significant differences exist in certain ways of coping, the resilient behavior, and between it and most of the coping modes expressed by different types of peer violence among spectators. Also, it is confirmed that the scale TSPV developed for this study is valid and reliable

Influence of diabetes on ambulation and inflammation in men and women with symptomatic peripheral artery disease

AbstractObjectiveTo determine whether diabetes and sex were factors associated with ambulatory function, endothelial cell inflammation, oxidative stress, and apoptosis, and with circulating biomarkers of inflammation and antioxidant capacity in patients with peripheral artery disease (PAD) and claudication.Materials/MethodsAmbulatory function of 180 symptomatic men and women with PAD was assessed during a graded maximal treadmill test, 6-minute walk test, and 4-meter walk test. Patients were further characterized on endothelial effects of circulating factors present in the sera using a cell culture-based bioassay on primary human arterial endothelial cells, and on circulating inflammatory and vascular biomarkers.ResultsMen and women with diabetes had greater prevalence (p = 0.007 and p = 0.015, respectively) of coronary artery disease (CAD) than patients without diabetes. To assure that this difference did not influence planned comparisons, the data set was stratified on CAD. Diabetic men with CAD had a lower peak walking time (PWT) during the treadmill test and a slower 4-meter gait speed compared to non-diabetic men with CAD (p < 0.05). Diabetic women with CAD had a lower PWT compared to their non-diabetic counterparts (p < 0.01). Additionally, diabetic men with CAD had higher pigment epithelium-derived factor (p < 0.05) than their non-diabetic counterparts, and diabetic women with CAD had higher leptin (p < 0.01) and interleukin-8 levels (p < 0.05).ConclusionsIn patients with PAD, diabetic men and women with CAD had more severe claudication than their non-diabetic counterparts, as measured by shorter PWT, and the men had further ambulatory impairment manifested by slower 4-meter gait speed. Furthermore, the diabetic patients with CAD had elevations in interleukin-8, leptin, and PEDF

Le FORUM, Vol. 35 No. 1

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