Increased Frequency and Compromised Function of T Regulatory Cells in Systemic Sclerosis (SSc) Is Related to a Diminished CD69 and TGFβ Expression

Contains fulltext : 80239.pdf (publisher's version ) (Open Access)BACKGROUND: Regulatory T cells (Tregs) are essential in the control of tolerance. Evidence implicates Tregs in human autoimmune conditions. Here we investigated their role in systemic sclerosis (SSc). METHODS/PRINCIPAL FINDINGS: Patients were subdivided as having limited cutaneous SSc (lcSSc, n = 20) or diffuse cutaneous SSc (dcSSc, n = 48). Further subdivision was made between early dcSSc (n = 24) and late dcSSc (n = 24) based upon the duration of disease. 26 controls were studied for comparison. CD3+ cells were isolated using FACS and subsequently studied for the expression of CD4, CD8, CD25, FoxP3, CD127, CD62L, GITR, CD69 using flow cytometry. T cell suppression assays were performed using sorted CD4CD25(high)CD127(-) and CD4CD25(low)CD127(high) and CD3(+) cells. Suppressive function was correlated with CD69 surface expression and TGFbeta secretion/expression. The frequency of CD4(+)CD25(+) and CD25(high)FoxP3(high)CD127(neg) T cells was highly increased in all SSc subgroups. Although the expression of CD25 and GITR was comparable between groups, expression of CD62L and CD69 was dramatically lower in SSc patients, which correlated with a diminished suppressive function. Co-incubation of Tregs from healthy donors with plasma from SSc patients fully abrogated suppressive activity. Activation of Tregs from healthy donors or SSc patients with PHA significantly up regulated CD69 expression that could be inhibited by SSc plasma. CONCLUSIONS/SIGNIFICANCE: These results indicate that soluble factors in SSc plasma inhibit Treg function specifically that is associated with altered Treg CD69 and TGFbeta expression. These data suggest that a defective Treg function may underlie the immune dysfunction in systemic sclerosis

Effect of maternal Schistosoma mansoni infection and praziquantel treatment during pregnancy on Schistosoma mansoni infection and immune responsiveness among offspring at age five years.

INTRODUCTION: Offspring of Schistosoma mansoni-infected women in schistosomiasis-endemic areas may be sensitised in-utero. This may influence their immune responsiveness to schistosome infection and schistosomiasis-associated morbidity. Effects of praziquantel treatment of S. mansoni during pregnancy on risk of S. mansoni infection among offspring, and on their immune responsiveness when they become exposed to S. mansoni, are unknown. Here we examined effects of praziquantel treatment of S. mansoni during pregnancy on prevalence of S. mansoni and immune responsiveness among offspring at age five years. METHODS: In a trial in Uganda (ISRCTN32849447, http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women treated with praziquantel or placebo during pregnancy were examined for S. mansoni infection and for cytokine and antibody responses to SWA and SEA, as well as for T cell expression of FoxP3, at age five years. RESULTS: Of the 1343 children examined, 32 (2.4%) had S. mansoni infection at age five years based on a single stool sample. Infection prevalence did not differ between children of treated or untreated mothers. Cytokine (IFNγ, IL-5, IL-10 and IL-13) and antibody (IgG1, Ig4 and IgE) responses to SWA and SEA, and FoxP3 expression, were higher among infected than uninfected children. Praziquantel treatment of S. mansoni during pregnancy had no effect on immune responses, with the exception of IL-10 responses to SWA, which was higher in offspring of women that received praziquantel during pregnancy than those who did not. CONCLUSION: We found no evidence that maternal S. mansoni infection and its treatment during pregnancy influence prevalence and intensity of S. mansoni infection or effector immune response to S. mansoni infection among offspring at age five years, but the observed effects on IL-10 responses to SWA suggest that maternal S. mansoni and its treatment during pregnancy may affect immunoregulatory responsiveness in childhood schistosomiasis. This might have implications for pathogenesis of the disease

Use of psychotropic drugs before pregnancy and the risk for induced abortion: population-based register-data from Finland 1996-2006

<p>Abstract</p> <p>Background</p> <p>Some, though not all studies have reported an increased risk for mental health problems after an induced abortion. Problems with design and data have compromised these studies and the generalisation of their results.</p> <p>Methods</p> <p>The Finnish Medication and Pregnancy database (N = 622 671 births and 114 518 induced abortions for other than fetal reasons) in 1996-2006 was utilised to study the use of psychotropic drugs in the three months before a pregnancy ending in a birth or an induced abortion.</p> <p>Results</p> <p>In total 2.1% of women with a birth and 5.1% of women with an induced abortion had used a psychotropic medicine 0-3 months before pregnancy. Psychotropic drug users terminated their pregnancies (30.9%) more often than other pregnant women (15.5%). Adjustment for background characteristics explained one third of this elevated risk, but the risk remained significantly increased among users of psychotropic medicine (OR 1.94, 95% confidence intervals 1.87-2.02). A similar risk was found for first pregnancies (30.1% vs. 18.9%; adjusted OR 1.53, 95% confidence intervals 1.42-1.65). The rate for terminating pregnancy was the highest for women using hypnotics and sedatives (35.6% for all pregnancies and 29.1% for first pregnancies), followed by antipsychotics (33.9% and 36.0%) and antidepressants (32.0% and 32.1%).</p> <p>Conclusions</p> <p>The observed increased risk for induced abortion among women with psychotropic medication highlighs the importance to acknowledge the mental health needs of women seeking an induced abortion. Further studies are needed to establish the impact of pre-existing differences in mental health on mental health outcomes of induced abortions compared to outcomes of pregnancies ending in a birth.</p

Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis

In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci

Highly Effective Therapy for Maternal Malaria Associated With a Lower Risk of Vertical Transmission

Background. The epidemiology of congenital malaria was investigated in a hospital-based malaria surveillance study in Papua, Indonesia

Prevalence of positive depression screen among post miscarriage women- A cross sectional study

Background: Miscarriages are a common pregnancy complication affecting about 10–15% of pregnancies. Miscarriages may be associated with a myriad of psychiatric morbidity at various timelines after the event. Depression has been shown to affect about 10–20% of all women following a miscarriage. However, no data exists in the local setting informing on the prevalence of post-miscarriage depression. We set out to determine the prevalence of positive depression screen among women who have experienced a miscarriage at the Aga Khan University hospital, Nairobi. Methods: The study was cross-sectional in design. Patients who had a miscarriage were recruited at the post-miscarriage clinic review at the gynecology clinics at Aga Khan University Hospital, Nairobi. The Edinburgh postpartum depression scale was used to screen for depression in the patients. Prevalence was calculated from the percentage of patients achieving the cut –off score of 13 over the total number of patients. Results: A total of 182 patients were recruited for the study. The prevalence of positive depression screen was 34.1% since 62 of the 182 patients had a positive depression screen. Moreover, of the patients who had a positive depression screen, 21(33.1%) had thoughts of self-harm. Conclusion: A positive depression screen is present in 34.1% of women in our population two weeks after a miscarriage. Thoughts of self-harm are present in about a third of these women (33.1%) hence pointing out the importance of screening these women using the EPDS after a miscarriage

Analysis of the association between CD40 and CD40 ligand polymorphisms and systemic sclerosis.

Introduction: The aim of the present study was to investigate the possible role of CD40 and CD40 ligand (CD40LG) genes in the susceptibility and phenotype expression of systemic sclerosis (SSc). Methods: In total, 2,670 SSc patients and 3,245 healthy individuals from four European populations (Spain, Germany, The Netherlands, and Italy) were included in the study. Five single-nucleotide polymorphisms (SNPs) of CD40 (rs1883832, rs4810485, rs1535045) and CD40LG (rs3092952, rs3092920) were genotyped by using a predesigned TaqMan allele-discrimination assay technology. Meta-analysis was assessed to determine whether an association exists between the genetic variants and SSc or its main clinical subtypes. Results: No evidence of association between CD40 and CD40LG genes variants and susceptibility to SSc was observed. Similarly, no significant statistical differences were observed when SSc patients were stratified by the clinical subtypes, the serologic features, and pulmonary fibrosis. Conclusions: Our results do not suggest an important role of CD40 and CD40LG gene polymorphisms in the susceptibility to or clinical expression of SSc

THE AFTERCARE SURVEY:Assessment and intervention practices after brain tumour surgery in Europe

Introduction People with gliomas need specialized neurosurgical, neuro-oncological, psycho-oncological, and neuropsychological care. The role of language and cognitive recovery and rehabilitation in patients’ well-being and resumption of work is crucial, but there are no clear guidelines for the ideal timing and character of assessments and interventions. The goal of the present work was to describe representative (neuro)psychological practices implemented after brain surgery in Europe. Methods An online survey was addressed to professionals working with individuals after brain surgery. We inquired about the assessments and interventions and the involvement of caregivers. Additionally, we asked about recommendations for an ideal assessment and intervention plan. Results Thirty-eight European centres completed the survey. Thirty of them offered at least one post-surgical (neuro)psychological assessment, mainly for language and cognition, especially during the early recovery stage and at long-term. Twenty-eight of the participating centres offered post-surgical therapies. Patients who stand the highest chances of being included in evaluation and therapy post-surgically are those who underwent awake brain surgery, harboured a low-grade glioma, or showed poor recovery. Nearly half of the respondents offer support programs to caregivers, and all teams recommend them. Treatments differed between these offered to individuals with low-grade glioma versus those with high-grade glioma. The figure of caregiver is not yet fully recognized in the recovery phase. Conclusion We stress the need for more complete rehabilitation plans, including the emotional and health-related aspects of recovery. In respondents´ opinions, assessment and rehabilitation plans should also be individually tailored and goal-directed (e.g., professional reinsertion)

Significance Analysis of Tourist Sports Events

Import 04/11/2015Cílem této bakalářské práce je popsání významu sportovních akcí v cestovním ruchu. Práce je rozdělena do dvou částí. První část představuje teoretická východiska zaměřená na cestovní ruch, sportovní událost, sportovní marketing a metody použité v práci. Druhá část práce obsahuje analýzu mezinárodních sportovních událostí v podobě olympijských her, Mistrovství světa ve fotbale. Podrobněji analyzuji sportovní události v České republice v roce 2015, Mistrovství Evropy ve fotbale do 21 let, Světový pohár v Biatlonu, Halové Mistrovství Evropy v Atletice a nejdůkladněji zkoumám Mistrovství světa v ledním hokeji 2015. Dotazník směřovaný pro návštěvníky hokejové sportovní události zkoumá dopady na turismus a cestovní ruch.The aim of this bachelor thesis is to describe significance analysis of tourist sports events. This thesis is divided in two parts. The first part presents the theoretical basis of tourist, sports events and sports marketing and methods used in work. The second part contains an analysis of international sporting events as the Olympic games and FIFA World Cup. I explain the influence of significant sport events in Czech republic in 2015, European Football Championship under 21 years, Biathlon World Cup and European Athletic Indoor Championships. I analyze in detail IIHF Hockey World Championship 2015. Questionnaire was made with questions focused on impact of tourism destinations and tourism.115 - Katedra managementuvýborn

Concurrent Detection of Circulating Minor Histocompatibility Antigen-Specific CD8+ T Cells in SCT Recipients by Combinatorial Encoding MHC Multimers

Allogeneic stem cell transplantation (SCT) is a potentially curative treatment for patients with hematologic malignancies. Its therapeutic effect is largely dependent on recognition of minor histocompatibility antigens (MiHA) by donor-derived CD8+ T cells. Therefore, monitoring of multiple MiHA-specific CD8+ T cell responses may prove to be valuable for evaluating the efficacy of allogeneic SCT. In this study, we investigated the use of the combinatorial encoding MHC multimer technique to simultaneously detect MiHA-specific CD8+ T cells in peripheral blood of SCT recipients. Feasibility of this approach was demonstrated by applying dual-color encoding MHC multimers for a set of 10 known MiHA. Interestingly, single staining using a fluorochrome- and Qdot-based five-color combination showed comparable results to dual-color staining for most MiHA-specific CD8+ T cell responses. In addition, we determined the potential value of combinatorial encoding MHC multimers in MiHA identification. Therefore, a set of 75 candidate MiHA peptides was predicted from polymorphic genes with a hematopoietic expression profile and further selected for high and intermediate binding affinity for HLA-A2. Screening of a large cohort of SCT recipients resulted in the detection of dual-color encoded CD8+ T cells following MHC multimer-based T cell enrichment and short ex vivo expansion. Interestingly, candidate MiHA-specific CD8+ T cell responses for LAG3 and TLR10 derived polymorphic peptides could be confirmed by genotyping of the respective SNPs. These findings demonstrate the potency of the combinatorial MHC multimer approach in the monitoring of CD8+ T cell responses to known and potential MiHA in limited amounts of peripheral blood from allogeneic SCT recipients