Visualization and functional characterization of T-T cell interactions in vivo

To define the T-T cell interactions during differentiation of naïve CD4+ T helper cells in vivo displaying the interactions of naïve CD4+ and differentiated type 2 (TH2) T helper cells by measuring specific T helper (TH) cytokines. The homing capacity of naïve T cells bearing a T cell receptor (TCR) specific for influenza hemagglutinin (HA) or TH2 cells bearing a TCR specific for ovalbumin (OVA) was analyzed in draining lymph nodes of naïve murine BALB/c recipients after immunization and peptide challenge in vivo. T cell homing was visualized by flow cytometry (FACS) and fluorescence microscopy. For measuring different T cell specific cytokines we used established systems as Enzyme-Linked-Immunosorbent Assay (ELISA) and Enzyme-Linked-Immunospot-(ELISPOT) Assay for interferon(IFN)-γ and CT.4S assay and ELISPOT for IL-4 analysis. We showed that naïve and TH2 cells migrate with similar dynamics into draining lymph nodes and were found in close vicinity in T cell areas, when driven by antigen in complete Freunds’ adjuvant (CFA). Under these conditions, TH2 cells prevented CFA-mediated TH1-induction and deviated the differentiation of naïve TH cells toward a TH2 phenotype. OVA- TH2 cells induced TH2-differentiation in naïve T cells exclusively, if naïve and TH2 memory cells were both activated simultaneously in the same lymph node. ‘TH2’-cells from IL-4-/- mice were unable to affect CFA-mediated TH1-induction showing that TH2-derived IL-4 was strictly required to deviate naïve HA TH cells toward a TH2 phenotype. Among the various signals capable of promoting TH2 differentiation IL-4 is one of the most important factor for differentiation of naïve T cells into TH2 phenotype. Direct, IL-4-mediated, T-T cell interactions could be measured and demonstrated that TH2 derived IL-4 under restricted conditions plays a major role in TH cell differentiation in vivo

Kimberley Transitions, Collaborating to Care for Our Common Home: Beginnings...

This scoping paper is a preliminary introduction to the aspirations, interrelated literature and research involved in development of the Kimberley Transitions Project. Our focus is on Western Australia’s Kimberley region, a landscape of immense natural and cultural significance. Along with the rest of Australia, and indeed the world in which we all live, the Kimberley is on the verge of major climate, political, social and economic change. The direction of changes being proposed by governments and industry are regularly criticised, both globally and locally, by individuals and organisations concerned about damage to its rich biodiversity and cultural integrity. With the aim of collaboratively generating Kimberley-based responses grounded in local knowledges, a mix of disciplines and emerging international theories, scholars and relevant groups have come together to form a Kimberley-wide practical and shared research agenda. One of the key influences behind the project is an international transitions movement which aims to generate collaborative change incorporating a process of transition. Locally identified issues using local knowledges and capacity are central to its evolution. A conceptual and theoretical framing known as ‘transitions discourse’ is also emerging internationally and nationally, one that foregrounds diverse epistemologies and challenges mainstream economics and associated ideologies, such as neoliberalism. Via the Kimberley Transitions project, Kimberley-based researchers and collaborators aim to support and further document social, cultural and economic change inspired by the transitions movement and informed by transition discourses. It has the Kimberley landscape and people at its heart; a transformative approach featuring cultural healing, intellectual rigour and an ethos aimed at enduring, practical and interconnected sustainable outcomes.https://researchonline.nd.edu.au/nulungu_research/1001/thumbnail.jp

Gender differences in the association of individual social class and neighbourhood unemployment rate with prevalent type 2 diabetes mellitus: a cross-sectional study from the DIAB-CORE consortium

OBJECTIVE: To analyse gender differences in the relationship of individual social class, employment status and neighbourhood unemployment rate with present type 2 diabetes mellitus (T2DM). DESIGN: Five cross-sectional studies. SETTING: Studies were conducted in five regions of Germany from 1997 to 2006. PARTICIPANTS: The sample consisted of 8871 individuals residing in 226 neighbourhoods from five urban regions. PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalent T2DM. RESULTS: We found significant multiplicative interactions between gender and the individual variables–—social class and employment status. Social class was statistically significantly associated with T2DM in men and women, whereby this association was stronger in women (lower vs higher social class: OR 2.68 (95% CIs 1.66 to 4.34)) than men (lower vs higher social class: OR 1.78 (95% CI 1.22 to 2.58)). Significant associations of employment status and T2DM were only found in women (unemployed vs employed: OR 1.73 (95% CI 1.02 to 2.92); retired vs employed: OR 1.77 (95% CI 1.10 to 2.84); others vs employed: OR 1.64 (95% CI 1.01 to 2.67)). Neighbourhood unemployment rate was associated with T2DM in men (high vs low tertile: OR 1.52 (95% CI 1.18 to 1.96)). Between-study and between-neighbourhood variations in T2DM prevalence were more pronounced in women. The considered covariates helped to explain statistically the variation in T2DM prevalence among men, but not among women. CONCLUSIONS: Social class was inversely associated with T2DM in both men and women, whereby the association was more pronounced in women. Employment status only affected T2DM in women. Neighbourhood unemployment rate is an important predictor of T2DM in men, but not in women

Regional differences of macrovascular disease in Northeast and South Germany: the population-based SHIP-TREND and KORA-F4 studies

Abstract Background Previous studies found regional differences in the prevalence and incidence of type 2 diabetes between Northeast and South of Germany. The aim of this study was to investigate if regional variations are also present for macrovascular disease in people with type 2 diabetes and in the general population. A further aim was to investigate if traditional risk factors of macrovascular complications can explain these regional variations. Methods Data of persons aged 30–79 from two regional population-based studies, SHIP-TREND (Northeast Germany, 2008–2012, n = 2539) and KORA-F4 (South Germany, 2006–2008, n = 2932), were analysed. Macrovascular disease was defined by self-reported previous myocardial infarction, stroke or coronary angiography. Multivariable logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI) for prevalence of macrovascular disease in persons with type 2 diabetes and in the general population. Results The prevalence of macrovascular disease in persons with type 2 diabetes and in the general population was considerably higher in the Northeast (SHIP-TREND: 32.8 and 12.0%) than in the South of Germany (KORA-F4: 24.9 and 8.8%), respectively. The odds of macrovascular disease in persons with type 2 diabetes was 1.66 (95% CI: 1.11–2.49) in the Northeast in comparison to the South after adjustment for sex, age, body mass index, hypertension, hyperlipidemia and smoking. In the general population, SHIP-TREND participants also had a significantly increased odds of macrovascular disease compared to KORA-F4 participants (OR = 1.63, 95% CI: 1.33–2.00). After excluding coronary angiography (myocardial infarction or stroke only), the ORs for region decreased in all models, but the difference between SHIP-TREND and KORA-F4 participants was still significant in the age- and sex-adjusted model for the general population (OR = 1.34, 95% CI: 1.01–1.78). Conclusions This study provides an indication for regional differences in macrovascular disease, which is not explained by traditional risk factors. Further examinations of other risk factors, such as regional deprivation or geographical variations in medical care services are needed

Blood pressure and lipid management fall far short in persons with type 2 diabetes: results from the DIAB-CORE Consortium including six German population-based studies

Background: Although most deaths among patients with type 2 diabetes (T2D) are attributable to cardiovascular disease, modifiable cardiovascular risk factors appear to be inadequately treated in medical practice. The aim of this study was to describe hypertension, dyslipidemia and medical treatment of these conditions in a large population-based sample. Methods: The present analysis was based on the DIAB-CORE project, in which data from five regional population-based studies and one nationwide German study were pooled. All studies were conducted between 1997 and 2006. We assessed the frequencies of risk factors and co-morbidities, especially hypertension and dyslipidemia, in participants with and without T2D. The odds of no or insufficient treatment and the odds of pharmacotherapy were computed using multivariable logistic regression models. Types of medication regimens were described. Results: The pooled data set comprised individual data of 15, 071 participants aged 45–74 years, including 1287 (8.5%) participants with T2D. Subjects with T2D were significantly more likely to have untreated or insufficiently treated hypertension, i.e. blood pressure of > = 140/90 mmHg (OR = 1.43, 95% CI 1.26-1.61) and dyslipidemia i.e. a total cholesterol/HDL-cholesterol ratio > = 5 (OR = 1.80, 95% CI 1.59-2.04) than participants without T2D. Untreated or insufficiently treated blood pressure was observed in 48.9% of participants without T2D and in 63.6% of participants with T2D. In this latter group, 28.0% did not receive anti-hypertensive medication and 72.0% were insufficiently treated. In non-T2D participants, 28.8% had untreated or insufficiently treated dyslipidemia. Of all participants with T2D 42.5% had currently elevated lipids, 80.3% of these were untreated and 19.7% were insufficiently treated. Conclusions: Blood pressure and lipid management fall short especially in persons with T2D across Germany. The importance of sufficient risk factor control besides blood glucose monitoring in diabetes care needs to be emphasized in order to prevent cardiovascular sequelae and premature death

which marker is best for prediction? Pooled analysis of four German population-based cohort studies and comparison with a nationwide cohort study

Objective To compare the association between different anthropometric measurements and incident type 2 diabetes mellitus (T2DM) and to assess their predictive ability in different regions of Germany. Methods Data of 10 258 participants from 4 prospective population-based cohorts were pooled to assess the association of body weight, body mass index (BMI), waist circumference (WC), waist-to-hip-ratio (WHR) and waist-to-height-ratio (WHtR) with incident T2DM by calculating HRs of the crude, adjusted and standardised markers, as well as providing receiver operator characteristic (ROC) curves. Differences between HRs and ROCs for the different anthropometric markers were calculated to compare their predictive ability. In addition, data of 3105 participants from the nationwide survey were analysed separately using the same methods to provide a nationally representative comparison. Results Strong associations were found for each anthropometric marker and incidence of T2DM. Among the standardised anthropometric measures, we found the strongest effect on incident T2DM for WC and WHtR in the pooled sample (HR for 1 SD difference in WC 1.97, 95% CI 1.75 to 2.22, HR for WHtR 1.93, 95% CI 1.71 to 2.17 in women) and in female DEGS participants (HR for WC 2.24, 95% CI 1.91 to 2.63, HR for WHtR 2.10, 95% CI 1.81 to 2.44), whereas the strongest association in men was found for WHR among DEGS participants (HR 2.29, 95% CI 1.89 to 2.78). ROC analysis showed WHtR to be the strongest predictor for incident T2DM. Differences in HR and ROCs between the different markers confirmed WC and WHtR to be the best predictors of incident T2DM. Findings were consistent across study regions and age groups (<65 vs ≥65 years). Conclusions We found stronger associations between anthropometric markers that reflect abdominal obesity (ie, WC and WHtR) and incident T2DM than for BMI and weight. The use of these measurements in risk prediction should be encouraged

Anthropometric markers and their association with incident type 2 diabetes mellitus: which marker is best for prediction? Pooled analysis of four German population-based cohort studies and comparison with a nationwide cohort study

Objective: To compare the association between different anthropometric measurements and incident type 2 diabetes mellitus (T2DM) and to assess their predictive ability in different regions of Germany. Methods: Data of 10 258 participants from 4 prospective population-based cohorts were pooled to assess the association of body weight, body mass index (BMI), waist circumference (WC), waist-to-hip-ratio (WHR) and waist-to-height-ratio (WHtR) with incident T2DM by calculating HRs of the crude, adjusted and standardised markers, as well as providing receiver operator characteristic (ROC) curves. Differences between HRs and ROCs for the different anthropometric markers were calculated to compare their predictive ability. In addition, data of 3105 participants from the nationwide survey were analysed separately using the same methods to provide a nationally representative comparison. Results: Strong associations were found for each anthropometric marker and incidence of T2DM. Among the standardised anthropometric measures, we found the strongest effect on incident T2DM for WC and WHtR in the pooled sample (HR for 1 SD difference in WC 1.97, 95% CI 1.75 to 2.22, HR for WHtR 1.93, 95% CI 1.71 to 2.17 in women) and in female DEGS participants (HR for WC 2.24, 95% CI 1.91 to 2.63, HR for WHtR 2.10, 95% CI 1.81 to 2.44), whereas the strongest association in men was found for WHR among DEGS participants (HR 2.29, 95% CI 1.89 to 2.78). ROC analysis showed WHtR to be the strongest predictor for incident T2DM. Differences in HR and ROCs between the different markers confirmed WC and WHtR to be the best predictors of incident T2DM. Findings were consistent across study regions and age groups

Comparative Study of the Sensitivity of Different Diagnostic Methods for the Laboratory Diagnosis of Buruli Ulcer Disease

Background. Several diagnostic laboratory methods are available for case confirmation of Buruli ulcer disease. This study assessed the sensitivity of various diagnostic tests in relation to clinical presentation of the disease, type of diagnostic specimen, and treatment history. Methods. Swab samples, 3-mm punch biopsy tissue specimens, and surgically excised tissue specimens from 384 individuals with suspected Buruli ulcer disease were obtained at 9 different study sites in Ghana and were evaluated with dry reagent-based polymerase chain reaction (PCR), microscopic examination, culture, and histopathological analysis. The study subjects presented with nonulcerative and ulcerative lesions and were divided into 3 treatment groups: (1) previously untreated patients scheduled for antimycobacterial treatment, (2) patients treated with surgery alone, and (3) patients treated with surgery in combination with previous antimycobacterial treatment. Results. Of 384 suspected cases of Buruli ulcer disease, 268 were confirmed by at least 1 positive test result. The overall sensitivity of PCR (85%) was significantly higher than that of microscopic examination (57%) and culture (51%). After data were stratified by treatment group, type of lesion, and diagnostic specimen type, analysis revealed that PCR of 3-mm punch biopsy tissue specimens (obtained from previously untreated nonulcerative lesions) and of swab samples (obtained from previously untreated ulcers) had the highest diagnostic sensitivity (94% and 90%, respectively). Although duration of the disease did not significantly influence the sensitivity of any test, previous antimycobacterial treatment was significantly associated with decreased sensitivity of PCR and culture. Conclusions. Across all subgroups, PCR had the highest sensitivity. PCR assessment of 3-mm punch biopsy tissue specimens proved to be the best diagnostic tool for nonulcerative lesions, and PCR assessment of swab samples was the best diagnostic tool for ulcerative lesions. For monitoring of antimycobacterial treatment success within controlled trials, however, only culture is appropriat