Does Hepatitis C Virus Infection Increase Risk for Stroke? A Population-Based Cohort Study

BACKGROUND: The relationship between hepatitis C virus infection and risk of stroke remains inconsistent. This study evaluates the risk of stroke in association with chronic hepatitis C infection in a longitudinal population-based cohort. METHODS: We identified 4,094 adults newly diagnosed with hepatitis C infection in 2002-2004 from the Taiwan National Health Insurance Research Database. Comparison group consisted of 16,376 adults without hepatitis C infection randomly selected from the same dataset, frequency matched by age and sex. Events of stroke from 2002-2008 were ascertained from medical claims (International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM, codes 430-438). Multivariate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for potential associated factors including HCV infection, age, sex, low-income status, urbanization, cessation of cigarette smoking, alcohol-related illness, obesity, history of chronic diseases and medication use. FINDINGS: During 96,752 person-years of follow-up, there were 1981 newly diagnosed stroke cases. The HRs of stroke associated with medical conditions such as hypertension, diabetes and heart disease were 1.48 (95% CI 1.33 to 1.65), 1.23 (95% CI 1.11 to 1.36) and 1.17 (95% CI 1.06 to 1.30), respectively, after adjustment for covariates. The cumulative risk of stroke for people with hepatitis C and without hepatitis C infections was 2.5% and 1.9%, respectively (p<0.0001). Compared with people without hepatitis C infection, the adjusted HR of stroke was 1.27 (95% CI 1.14 to 1.41) for people with hepatitis C infection. CONCLUSION: Chronic hepatitis C infection increases stroke risk and should be considered an important and independent risk factor

Association of predicted 10 years cardiovascular mortality risk with duration of HIV infection and antiretroviral therapy among HIV-infected individuals in Durban, South Africa

Background: South Africa has the largest population of human immunodeficiency virus (HIV) infected patients on antiretroviral therapy (ART) realising the benefits of increased life expectancy. However, this population may be susceptible to cardiovascular disease (CVD) development, due to the chronic consequences of a lifestyle-related combination of risk factors, HIV infection and ART. We predicted a 10-year cardiovascular mortality risk in an HIV-infected population on long-term ART, based on their observed metabolic risk factor profile. Methods: We extracted data from hospital medical charts for 384 randomly selected HIV-infected patients aged ≥ 30 years. We defined metabolic syndrome (MetS) subcomponents using the International Diabetes Federation definition. A validated non-laboratory-based model for predicting a 10-year CVD mortality risk was applied and categorised into five levels, with the thresholds ranging from very low-risk ( 30%). Results: Among the 384 patients, with a mean (± standard deviation) age of 42.90 ± 8.20 years, the proportion of patients that were overweight/obese was 53.3%, where 50.9% had low high-density lipoprotein (HDL) cholesterol and 21 (17.5%) had metabolic syndrome. A total of 144 patients with complete data allowed a definitive prediction of a 10-year CVD mortality risk. 52% (95% CI 44-60) of the patients were stratified to very low risk ( 30%) of 10-year CVD mortality. The CVD risk grows with increasing age (years), 57.82 ± 6.27 among very high risk and 37.52 ± 4.50; p < 0.001 in very low risk patients. Adjusting for age and analysing CVD risk mortality as a continuous risk score, increasing duration of HIV infection (p = 0.002) and ART (p = 0.007) were significantly associated with increased predicted 10 year CVD mortality risk. However, there was no association between these factors and categorised CVD mortality risk as per recommended scoring thresholds. Conclusions: Approximately 1 in 10 HIV-infected patients is at very high risk of predicted 10-year CVD mortality in our study population. Like uninfected individuals, our study found increased age as a major predictor of 10-year mortality risk and high prevalence of metabolic syndrome. Additional CVD mortality risk due to the duration of HIV infection and ART was seen in our population, further studies in larger and more representative study samples are encouraged. It recommends an urgent need for early planning, prevention and management of metabolic risk factors in HIV populations, at the point of ART initiation

Smoking cessation, alcohol intake and transient increase in the risk of metabolic syndrome among Japanese smokers at one health checkup institution

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome (MetS) is potentially effective measures to identify individuals at risk of coronary heart disease (CHD) and type 2 diabetes. To verify the hypothesis that smoking cessation may increase the risk of MetS, a follow-up study taking drinking habit into account was conducted for the examinees at one health checkup institution.</p> <p>Methods</p> <p>Subjects were the examinees who visited the Institution for Disease Prevention and Health Checkup, Seirei Mikatabara Hospital for annual health checkup from January 2003 to December 2006. Among them, 5,872 smokers (5,479 men, 93.3%) free from MetS at the first year in two consecutive years were selected. For the long term follow-up, the risk of MetS among those who maintained their nonsmoking status for 1 or 2 additional years was evaluated.</p> <p>Results</p> <p>Relative to non-quitters, quitters showed a significantly elevated adjusted hazard ratio (aHR) of MetS in two consecutive years (aHR = 2.09, 95% confidence interval: 1.43–3.04, <it>P </it>< 0.001). The aHR was higher among the quitters who had a drinking habit at the first year (aHR = 2.42, 95% CI: 1.48–3.94, <it>P </it>< 0.001). Analyses for 1 or 2 additional years of follow-up revealed that this significant increase in risk of MetS was transient.</p> <p>Conclusion</p> <p>The present study revealed that smoking cessation elevated the risk of MetS significantly, especially among drinkers. Although this detrimental effect of smoking cessation was found to be during only a short term, our results suggested that we should take measures, presumably including interventions for alcohol cessation, not to expose smoking quitters to this adverse effect. Further investigations are required to confirm our findings.</p

Chemotactic and Inflammatory Responses in the Liver and Brain Are Associated with Pathogenesis of Rift Valley Fever Virus Infection in the Mouse

Rift Valley fever virus (RVFV) is a major human and animal pathogen associated with severe disease including hemorrhagic fever or encephalitis. RVFV is endemic to parts of Africa and the Arabian Peninsula, but there is significant concern regarding its introduction into non-endemic regions and the potentially devastating effect to livestock populations with concurrent infections of humans. To date, there is little detailed data directly comparing the host response to infection with wild-type or vaccine strains of RVFV and correlation with viral pathogenesis. Here we characterized clinical and systemic immune responses to infection with wild-type strain ZH501 or IND vaccine strain MP-12 in the C57BL/6 mouse. Animals infected with live-attenuated MP-12 survived productive viral infection with little evidence of clinical disease and minimal cytokine response in evaluated tissues. In contrast, ZH501 infection was lethal, caused depletion of lymphocytes and platelets and elicited a strong, systemic cytokine response which correlated with high virus titers and significant tissue pathology. Lymphopenia and platelet depletion were indicators of disease onset with indications of lymphocyte recovery correlating with increases in G-CSF production. RVFV is hepatotropic and in these studies significant clinical and histological data supported these findings; however, significant evidence of a pro-inflammatory response in the liver was not apparent. Rather, viral infection resulted in a chemokine response indicating infiltration of immunoreactive cells, such as neutrophils, which was supported by histological data. In brains of ZH501 infected mice, a significant chemokine and pro-inflammatory cytokine response was evident, but with little pathology indicating meningoencephalitis. These data suggest that RVFV pathogenesis in mice is associated with a loss of liver function due to liver necrosis and hepatitis yet the long-term course of disease for those that might survive the initial hepatitis is neurologic in nature which is supported by observations of human disease and the BALB/c mouse model

Prevalence and Determinants of Metabolic Syndrome among Women in Chinese Rural Areas

BACKGROUND AND AIMS: Metabolic syndrome (MS) is prevalent in recent years but few data is reported in the rural areas in China. The aim of this study was to examine MS prevalence and its risk factors among women in rural China. METHODS AND RESULTS: The Nantong Metabolic Syndrome Study (NMSS), a population based cross-sectional study, was conducted during 2007-2008 in Nantong, China. In person interviews, blood glucose and lipid measurements were completed for 13,505 female participants aged 18-74 years. The International Diabetes Federation (IDF), the US Third Report of the National Cholesterol Education Program, the Adult Treatment Panel (ATPIII) and modified ATPIII for Asian population has determined three criteria of MS. These criteria for MS were used and compared in this study. The prevalence of MS was 22.0%, 16.9% and 23.3% according to IDF, ATPIII and ATPIII-modified criteria, respectively. Levels of agreement of these criteria for MS were above 0.75. We found that vigorous-intensity of occupational physical activity was associated with a low prevalence of MS with OR of 0.76 (95% confidence interval (CI): 0.63-0.91). Rice wine drinkers (alcohol >12.8 g/day) had about 34% low risks of developing MS with OR of 0.66 (95% CI: 0.48-0.91), compared with non-drinkers. Odds ratio of MS was 1.81 (95% CI: 1.15-2.84) in women who smoked more than 20 pack-years, compared to non-smokers. Odds ratio of MS was 1.56 (95% CI: 1.25-1.95) in women who had familial history of diseases, including hypertension, diabetes and stroke, compared to women without familial history of those diseases. CONCLUSION: MS is highly prevalent among women in rural China. Both physical activity and rice wine consumption play a protective role, while family history and smoking are risk factors in MS development. Educational programs should be established for promoting healthy lifestyles and appropriate interventions in rural China

Spectral hole burning: examples from photosynthesis

The optical spectra of photosynthetic pigment–protein complexes usually show broad absorption bands, often consisting of a number of overlapping, ‘hidden’ bands belonging to different species. Spectral hole burning is an ideal technique to unravel the optical and dynamic properties of such hidden species. Here, the principles of spectral hole burning (HB) and the experimental set-up used in its continuous wave (CW) and time-resolved versions are described. Examples from photosynthesis studied with hole burning, obtained in our laboratory, are then presented. These examples have been classified into three groups according to the parameters that were measured: (1) hole widths as a function of temperature, (2) hole widths as a function of delay time and (3) hole depths as a function of wavelength. Two examples from light-harvesting (LH) 2 complexes of purple bacteria are given within the first group: (a) the determination of energy-transfer times from the chromophores in the B800 ring to the B850 ring, and (b) optical dephasing in the B850 absorption band. One example from photosystem II (PSII) sub-core complexes of higher plants is given within the second group: it shows that the size of the complex determines the amount of spectral diffusion measured. Within the third group, two examples from (green) plants and purple bacteria have been chosen for: (a) the identification of ‘traps’ for energy transfer in PSII sub-core complexes of green plants, and (b) the uncovering of the lowest k = 0 exciton-state distribution within the B850 band of LH2 complexes of purple bacteria. The results prove the potential of spectral hole burning measurements for getting quantitative insight into dynamic processes in photosynthetic systems at low temperature, in particular, when individual bands are hidden within broad absorption bands. Because of its high-resolution wavelength selectivity, HB is a technique that is complementary to ultrafast pump–probe methods. In this review, we have provided an extensive bibliography for the benefit of scientists who plan to make use of this valuable technique in their future research

The human cytomegalovirus ul11 protein interacts with the receptor tyrosine phosphatase cd45, resulting in functional paralysis of t cells

Human cytomegalovirus (CMV) exerts diverse and complex effects on the immune system, not all of which have been attributed to viral genes. Acute CMV infection results in transient restrictions in T cell proliferative ability, which can impair the control of the virus and increase the risk of secondary infections in patients with weakened or immature immune systems. In a search for new immunomodulatory proteins, we investigated the UL11 protein, a member of the CMV RL11 family. This protein family is defined by the RL11 domain, which has homology to immunoglobulin domains and adenoviral immunomodulatory proteins. We show that pUL11 is expressed on the cell surface and induces intercellular interactions with leukocytes. This was demonstrated to be due to the interaction of pUL11 with the receptor tyrosine phosphatase CD45, identified by mass spectrometry analysis of pUL11-associated proteins. CD45 expression is sufficient to mediate the interaction with pUL11 and is required for pUL11 binding to T cells, indicating that pUL11 is a specific CD45 ligand. CD45 has a pivotal function regulating T cell signaling thresholds; in its absence, the Src family kinase Lck is inactive and signaling through the T cell receptor (TCR) is therefore shut off. In the presence of pUL11, several CD45-mediated functions were inhibited. The induction of tyrosine phosphorylation of multiple signaling proteins upon TCR stimulation was reduced and T cell proliferation was impaired. We therefore conclude that pUL11 has immunosuppressive properties, and that disruption of T cell function via inhibition of CD45 is a previously unknown immunomodulatory strategy of CMV