Comparative Genotyping of Campylobacter jejuni Strains from Patients with Guillain-Barré Syndrome in Bangladesh

Background: Campylobacter jejuni is a common cause of acute gastroenteritis and is associated with post-infectious neuropathies such as the Guillain-Barré syndrome (GBS) and the Miller Fisher syndrome (MFS). We here present comparative genotyping of 49 C. jejuni strains from Bangladesh that were recovered from patients with enteritis or GBS. All strains were serotyped and analyzed by lipo-oligosaccharide (LOS) genotyping, amplified fragment length polymorphism (AFLP) analysis, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). Methodology/Principal Findings: C. jejuni HS:23 was a predominant serotype among GBS patients (50%), and no specific serotype was significantly associated with GBS compared to enteritis. PCR screening showed that 38/49 (78%) of strains could be assigned to LOS classes A, B, C, or E. The class A locus (4/7 vs 3/39; p<0.01) was significantly associated in the GBS-related strains as compared to enteritis strains. All GBS/oculomotor related strains contained the class B locus; which was also detected in 46% of control strains. Overlapping clonal groups were defined by MLST, AFLP and PFGE for strains from patients with gastroenteritis and GBS. MLST defined 22 sequence types (STs) and 7 clonal complexes including 7 STs not previously identified (ST-3742, ST-3741, ST-3743, ST-3748, ST-3968, ST-3969 and ST-3970). C. jejuni HS:23 strains from patients with GBS or enteritis were clonal and all strains belonged to ST-403 complex. Concordance between LOS class B and ST-403 complex was revealed. AFLP defined 25 different types at 90% similarity. The predominant AFLP type AF-20 coincided with the C. jejuni HS:23 and ST-403 complex. Conclusion/Significance: LOS genotyping, MLST, AFLP and PFGE helped to identify the HS:23 strains from GBS or enteritis patients as clonal. Overall, genotypes exclusive for enteritis or for GBS-related strains were not obtained although LOS class A was significantly associated with GBS str

Parameter and model uncertainty in a life-table model for fine particles (PM2.5): a statistical modeling study

<p>Abstract</p> <p>Background</p> <p>The estimation of health impacts involves often uncertain input variables and assumptions which have to be incorporated into the model structure. These uncertainties may have significant effects on the results obtained with model, and, thus, on decision making. Fine particles (PM_2.5) are believed to cause major health impacts, and, consequently, uncertainties in their health impact assessment have clear relevance to policy-making. We studied the effects of various uncertain input variables by building a life-table model for fine particles.</p> <p>Methods</p> <p>Life-expectancy of the Helsinki metropolitan area population and the change in life-expectancy due to fine particle exposures were predicted using a life-table model. A number of parameter and model uncertainties were estimated. Sensitivity analysis for input variables was performed by calculating rank-order correlations between input and output variables. The studied model uncertainties were (i) plausibility of mortality outcomes and (ii) lag, and parameter uncertainties (iii) exposure-response coefficients for different mortality outcomes, and (iv) exposure estimates for different age groups. The monetary value of the years-of-life-lost and the relative importance of the uncertainties related to monetary valuation were predicted to compare the relative importance of the monetary valuation on the health effect uncertainties.</p> <p>Results</p> <p>The magnitude of the health effects costs depended mostly on discount rate, exposure-response coefficient, and plausibility of the cardiopulmonary mortality. Other mortality outcomes (lung cancer, other non-accidental and infant mortality) and lag had only minor impact on the output. The results highlight the importance of the uncertainties associated with cardiopulmonary mortality in the fine particle impact assessment when compared with other uncertainties.</p> <p>Conclusion</p> <p>When estimating life-expectancy, the estimates used for cardiopulmonary exposure-response coefficient, discount rate, and plausibility require careful assessment, while complicated lag estimates can be omitted without this having any major effect on the results.</p

Exercise training with dietary counselling increases mitochondrial chaperone expression in middle-aged subjects with impaired glucose tolerance

<p>Abstract</p> <p>Background</p> <p>Insulin resistance and diabetes are associated with increased oxidative stress and impairment of cellular defence systems. Our purpose was to investigate the interaction between glucose metabolism, antioxidative capacity and heat shock protein (HSP) defence in different skeletal muscle phenotypes among middle-aged obese subjects during a long-term exercise and dietary intervention. As a sub-study of the Finnish Diabetes Prevention Study (DPS), 22 persons with impaired glucose tolerance (IGT) taking part in the intervention volunteered to give samples from the <it>vastus lateralis </it>muscle. Subjects were divided into two sub-groups (IGTslow and IGTfast) on the basis of their baseline myosin heavy chain profile. Glucose metabolism, oxidative stress and HSP expressions were measured before and after the 2-year intervention.</p> <p>Results</p> <p>Exercise training, combined with dietary counselling, increased the expression of mitochondrial chaperones HSP60 and glucose-regulated protein 75 (GRP75) in the <it>vastus lateralis </it>muscle in the IGTslow group and that of HSP60 in the IGTfast group. In cytoplasmic chaperones HSP72 or HSP90 no changes took place. In the IGTslow group, a significant positive correlation between the increased muscle content of HSP60 and the oxygen radical absorbing capacity values and, in the IGTfast group, between the improved VO_2maxvalue and the increased protein expression of GRP75 were found. Serum uric acid concentrations decreased in both sub-groups and serum protein carbonyl concentrations decreased in the IGTfast group.</p> <p>Conclusion</p> <p>The 2-year intervention up-regulated mitochondrial HSP expressions in middle-aged subjects with impaired glucose tolerance. These improvements, however, were not correlated directly with enhanced glucose tolerance.</p

Autoimmunity, hypogammaglobulinemia, lymphoproliferation and mycobacterial disease in patients with dominant activating mutations in STAT3

The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.</p