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Objective: The sequelae of increasing childhood obesity are of major concern. We assessed the association of BMI in late adolescence with diabetes mortality in midlife.Research Design and Methods: The BMI values of 2,294,139 Israeli adolescents (age 17.4 ± 0.3 years), measured between 1967 and 2010, were grouped by U.S. Centers for Disease Control and Prevention age/sex percentiles and by ordinary BMI values. The outcome, obtained by linkage with official national records, was death attributed to diabetes mellitus (DM) as the underlying cause. Cox proportional hazards models were applied.Results: During 42,297,007 person-years of follow-up (median, 18.4 years; range <1-44 years) there were 481 deaths from DM (mean age at death, 50.6 ± 6.6 years). There was a graded increase in DM mortality evident from the 25th to the 49th BMI percentile group onward and from a BMI of 20.0-22.4 kg/m2 onward. Overweight (85th to 94th percentiles) and obesity (the 95th percentile or higher), compared with the 5th to 24th percentiles, were associated with hazard ratios (HRs) of 8.0 (95% CI 5.7-11.3) and 17.2 (11.9-24.8) for DM mortality, respectively, after adjusting for sex, age, birth year, height, and sociodemographic variables. The HR for the 50th through 74th percentiles was 1.6 (95% CI 1.1-2.3). Findings persisted in a series of sensitivity analyses. The estimated population-attributable fraction for DM mortality, 31.2% (95% CI 26.6-36.1%) for the 1967-1977 prevalence of overweight and obesity at age 17, rose to a projected 52.1% (95% CI 46.4-57.4%) for the 2012-2014 prevalence.Conclusions: Adolescent BMI, including values within the currently accepted "normal" range, strongly predicts DM mortality up to the seventh decade. The increasing prevalence of childhood and adolescent overweight and obesity points to a substantially increased future adult DM burden. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Intravenous immunoglobulin (IVIG) has been widely used to treat various conditions, including inflammatory and autoimmune diseases. IVIG has been shown to have a direct influence on neutrophils, eosinophils and lymphocytes. However, many aspects IVIG's effect on neutrophils activation still remain unknown. OBJECTIVE: To evaluate the effect of IVIG on PMA-induced activation of neutrophils, with and without priming with TNF-a, in a series of in vitro experiments performed on whole blood. RESULTS: Our data coincided with well-known literature indicating that the effect of phorbol 12-myristate 13-acetate (PMA) on human leukocytes includes activation of neutrophils, monocytes and eosinophils, increase of chemiluminescence (CL) and induction of netosis, resulting in assembly of traps. In presence of IVIG (10 mg/mL), CL was reduced by 25% in response to PMA compared to PMA-induced leukocyte activation without IVIG. Decreasing IVIG concentration to 1 mg/mL and below did not inhibit PMA-induced activation of CL. PMA-induced activation after TNF-a priming resulted in approximately 50% increase of amplitude of CL response to PMA. Moreover, maximum CL was reached by minute 5, which was more rapid than in the absence of TNF-a-priming (in this case maximum CL was reached by minute 15). The IVIG concentrations did not affect morphological changes of leukocytes after sequential addition of TNF-a and PMA. IVIG had no effect on leukocyte content and on PMA-induced CL of primed leukocytes. Addition of IVIG under TNF-α priming significantly increased the number of traps in the smears in response to PMA activation. Of note, such an increase in the number of traps was depended on the IVIG concentration in plasma. CONCLUSION: In conclusion, we suggest that IVIG is able to reduce the degradation of traps under priming with TNF-α. Moreover, IVIG might switch the activation of primed leukocytes to netosis. [ABSTRACT FROM AUTHOR]

Introduction: Intravenous immunoglobulin (IVIG) has been widely used to treat various conditions, including inflammatory and autoimmune diseases. IVIG has been shown to have a direct influence on neutrophils, eosinophils and lymphocytes. However, many aspects IVIG's effect on neutrophils activation still remain unknown., Objective: To evaluate the effect of IVIG on PMA-induced activation of neutrophils, with and without priming with TNF-α, in a series of in vitro experiments performed on whole blood., Results: Our data coincided with well-known literature indicating that the effect of phorbol 12-myristate 13-acetate (PMA) on human leukocytes includes activation of neutrophils, monocytes and eosinophils, increase of chemiluminescence (CL) and induction of netosis, resulting in assembly of traps. In presence of IVIG (10 mg/mL), CL was reduced by 25% in response to PMA compared to PMA-induced leukocyte activation without IVIG. Decreasing IVIG concentration to 1 mg/mL and below did not inhibit PMA-induced activation of CL.PMA-induced activation after TNF-α priming resulted in approximately 50% increase of amplitude of CL response to PMA. Moreover, maximum CL was reached by minute 5, which was more rapid than in the absence of TNF-α-priming (in this case maximum CL was reached by minute 15).The IVIG concentrations did not affect morphological changes of leukocytes after sequential addition of TNF-α and PMA. IVIG had no effect on leukocyte content and on PMA-induced CL of primed leukocytes.Addition of IVIG under TNF-α priming significantly increased the number of traps in the smears in response to PMA activation. Of note, such an increase in the number of traps was depended on the IVIG concentration in plasma., Conclusion: In conclusion, we suggest that IVIG is able to reduce the degradation of traps under priming with TNF-α. Moreover, IVIG might switch the activation of primed leukocytes to netosis.

Background: Gastrointestinal (GI)-related autoantibodies (Abs) are rarely evaluated in autoimmune diseases (AID) other than inflammatory bowel disease, autoimmune hepatitis and celiac disease. Our aim was to determine the prevalence of these antibodies in a wide spectrum of AID., Methods: We examined 923 serum samples representing 18 AID and compared them with 338 samples from healthy subjects. We used the BioPlex 2200-immunoassay (Bio-Rad, USA) to test samples for the presence of IgA and IgG directed at gliadin (AGA), tissue-transglutaminase (tTG), and Saccharomyces cerevisiae (ASCA)., Results: Prevalence of IgA AGA was significantly higher in antiphospholipid syndrome (APS) (7.1 %, P=0.012) and in pemphigus vulgaris (25%, P =0.008) patients, as compared with healthy controls. Presence of IgG-AGA was more common among Crohn's disease (20.5%, P = 0.023) and rheumatoid arthritis (6.5%, P=0.027) patients. IgG anti tTG were frequently observed in APS (6.1%, P=0.012), in giant cell arteritis (11.5%, P=0.013) and in ulcerative colitis (11.1%, P=0.018) patients, and as expected, higher prevalence of ASCA (IgA 19.3% and IgG 27.7%) was found in Crohn's disease. IgG ASCA were also found in systemic lupus erythematosus (SLE) (4.5%, P=0.01), in Graves' disease (5.7%, P=0.018), in cryoglobulinemia (7.1%, P=0.006), and in patients with vasculitides (6.5%, P=0.002). In contrast, lower prevalence of IgG type AGA was found in SLE (P=0.034), cryoglobulinemia (P=0.019) and vasculitides (P=0.013) patients., Conclusions: Our findings suggest an association between GI-related- Abs and a wide spectrum of AID. The clinical implication of these findings is yet to be determined.