Fasting insulin and risk of cerebral infarction in a Japanese general population: The Jichi Medical School Cohort Study

Abstract Objective: We investigated the relation between fasting insulin (FI) and risk of cerebral infarction in a Japanese general population. Methods: The subjects were 2,610 men and women without past history of stroke or myocardial infarction and under treatment for diabetes, examined between 1992 and 1995 as part of the Jichi Medical School Cohort Study. The FI level was measured once at the baseline. Subjects were divided into quintiles by FI levels, and Cox's proportional hazard model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cerebral infarction. Results: During an average of 11.1 years of follow-up, 87 participants developed cerebral infarction. Crude incidence rates of FI quintiles 1-5 were 4.69, 2.35, 1.85, 2.77 and 3.30 per 1,000 person-years, respectively. The multivariate-adjusted HRs for cerebral infarction were 2.33 (95% CI, 1.10 -4.96) in quintile 1 (Q1), 1.25 (95% CI, 0.55 -2.84) in Q2, 1.68 (95% CI, 0.76 -3.70) in Q4 and 2.06 (95% CI, 0.94 -4.47) in Q5, using Q3 as the reference. Conclusions: The lowest FI level was associated with increased risk of cerebral infarction and the association between FI and risk of cerebral infarction appeared to be a U-shaped relationship

Influence of Media on Seasonal Influenza Epidemic Curves

Back ground: Theoretical investigations predicting the epidemic curves of seasonal influenza have been demonstrated so far; however, there is little empirical research using ever accumulated epidemic curves. The effects of vaccine coverage and information distribution on influenza epidemics were evaluated. Materials and Methods: Four indices for epidemics (i.e., onset-peak duration, onset-end duration, ratio of the onset-peak duration to onset-end duration and steepness of epidemic curves) were defined, and the correlations between these indices and anti-flu drug prescription dose, vaccine coverage, the volume of media and search trend on influenza through internet were analyzed. Epidemiological data on seasonal influenza epidemics from 2002/2003 to 2013/2014 excluding 2009/2010 season were collected from National Institute of Infectious Diseases of Japan. Results: The onset-peak duration and its ratio to onset-end duration correlated inversely with the volume of anti-flu drug prescription. Onset-peak duration correlated positively with media information volume on influenza. The steepness of the epidemic curve, and anti-flu drug prescription dose inversely correlated with the volume of media information. Pre-epidemic search trend and media volume on influenza correlated with the vaccine coverage in the season. Vaccine coverage had no strong effect on epidemic curve. Conclusion: Education through media has an effect on the epidemic curve of seasonal influenza

Class II phosphoinositide 3-kinase α-isoform regulates Rho, myosin phosphatase and contraction in vascular smooth muscle

We demonstrated previously that membrane depolarization and excitatory receptor agonists such as noradrenaline induce Ca(2+)-dependent Rho activation in VSM (vascular smooth muscle), resulting in MP (myosin phosphatase) inhibition through the mechanisms involving Rho kinase-mediated phosphorylation of its regulatory subunit MYPT1. In the present study, we show in de-endothelialized VSM strips that the PI3K (phosphoinositide 3-kinase) inhibitors LY294002 and wortmannin inhibited KCl membrane depolarization- and noradrenaline-induced Rho activation and MYPT1 phosphorylation, with concomitant inhibition of MLC (20-kDa myosin light chain) phosphorylation and contraction. LY294002 also augmented de-phosphorylation of MLC and resultantly relaxation in KCl-contracted VSM, whereas LY294002 was much less effective or ineffective under the conditions in which MP was inhibited by either a phosphatase inhibitor or a phorbol ester in Rho-independent manners. VSM express at least four PI3K isoforms, including the class I enzymes p110α and p110β and the class II enzymes PI3K-C2α and -C2β. The dose–response relationships of PI3K-inhibitor-induced inhibition of Rho, MLC phosphorylation and contraction were similar to that of PI3K-C2α inhibition, but not to that of the class I PI3K inhibition. Moreover, KCl and noradrenaline induced stimulation of PI3K-C2α in a Ca(2+)-dependent manner, but not of p110α or p110β. Down-regulation of PI3K-C2α expression by siRNA (small interfering RNA) inhibited contraction and phosphorylation of MYPT1 and MLC in VSM cells. Finally, intravenous wortmannin infusion induced sustained hypotension in rats, with inhibition of PI3K-C2α activity, GTP-loading of Rho and MYPT1 phosphorylation in the artery. These results indicate the novel role of PI3K-C2α in Ca(2+)-dependent Rho-mediated negative control of MP and thus VSM contraction