SIAH-1 interacts with the Kaposi's sarcoma-associated herpesvirus-encoded ORF45 protein and promotes its ubiquitylation and proteasomal degradation.

Kaposi's sarcoma-associated herpesvirus (KSHV), also referred to as human herpesvirus 8, is a potentially tumorigenic virus implicated in the etiology of Kaposi's sarcoma, primary effusion lymphoma, and some forms of multicentric Castleman's disease. The open reading frame 45 (ORF45) protein, encoded by the KSHV genome, is capable of inhibiting virus-dependent interferon induction and appears to be essential for both early and late stages of infection. In the present study, we show, both in yeast two-hybrid assays and in mammalian cells, that the ORF45 protein interacts with the cellular ubiquitin E3 ligase family designated seven in absentia homologue (SIAH). We provide evidence that SIAH-1 promotes the degradation of KSHV ORF45 through a RING domain-dependent mechanism and via the ubiquitin-proteasome system. Furthermore, our data indicate the involvement of SIAH-1 in the regulation of the expression of ORF45 in KSHV-infected cells. Since the availability of KSHV ORF45 is expected to influence the course of KSHV infection, our findings identify a novel biological role for SIAH proteins as modulators of virus infection.

Socioeconomic inequalities in exposure to environmental tobacco smoke in children in Israel.

BACKGROUND: Environmental tobacco smoke (ETS) exposure in infants and children causes more frequent and severe asthma attacks, respiratory infections, ear infections, and sudden infant death syndrome. The aim of this study was to measure ETS exposure in children in Israel (ages 4-11 years) using urinary cotinine measurements, in order to compare exposure levels to other international populations, and to assess predictors of ETS exposure in children in Israel. METHODS: A subset of children who participated in the National Health and Nutrition Survey (RAV- MABAT) in 2015-2016 were invited to participate in the Second Israel Biomonitoring Survey. We analyzed urinary cotinine and creatinine concentrations in 103 children. Parents of study participants were interviewed in person on children's exposure to ETS at home and in other environments and on sociodemographic variables. We calculated creatinine-adjusted and unadjusted urinary cotinine geometric means in children and analyzed associations in univariable and multivariable analyses, between sociodemographic variables and parental - reported exposure, and urinary cotinine concentrations. RESULTS: Based on urinary creatinine measurement, over 60% of children are exposed to ETS (compared to <40% based on parental report). Linear regression showed a positive association between urinary cotinine concentration and reported ETS exposure (p = 0.001). Mean cotinine concentration among children whose parents reported that they are exposed to ETS at home (5.1 µg/l) was significantly higher than the concentration among children whose parents reported they are not exposed to ETS at home (1.6 µg/l, p < 0.001). There was an inverse relationship between total family income and urinary cotinine concentration (p < 0.05). In a multivariable model adjusted for ethnicity and other factors, family income was a significant predictor of urinary cotinine level (p = 0.04, slope = -0.49). Geometric mean creatinine adjusted concentrations in children in the current study were higher than in children in Canada and selected European countries. CONCLUSIONS: We found evidence of widespread exposure to ETS in children in the study. There is an urgent need to protect children in Israel from exposure to ETS.

Exposure to environmental tobacco smoke in non - smoking adults in Israel: results of the second Israel biomonitoring survey.

BACKGROUND: Exposure to environmental tobacco smoke (ETS) increases the risk of heart and respiratory disease, cancer, and premature mortality in non-smoking individuals. Results from the first Israel Biomonitoring Study in 2011 showed that over 60% of non-smoking adults are exposed to ETS. The purpose of the current study was to assess whether policies to restrict smoking in public places have been associated with reductions in exposure to ETS, and to examine predictors of exposure. METHODS: We analyzed urinary cotinine and creatinine concentrations in 194 adult participants in the National Health and Nutrition (RAV MABAT) Survey in 2015-2016. Study participants were interviewed in person on smoking status and exposure to ETS. We calculated creatinine-adjusted and unadjusted urinary cotinine geometric means and medians among smokers and non-smokers. We analyzed associations in univariable analyses, between socio-demographic variables and self - reported exposure, and urinary cotinine concentrations. RESULTS: There was no reduction in geometric mean urinary cotinine levels in non-smokers in the current study (1.7 µg/g) compared to that in 2011 (1.6 µg/g). Median cotinine levels among the non - smoking Arab participants were higher in comparison to the Jewish and other participants (2.97 versus 1.56 µg/l, p = 0.035). Participants who reported that they were exposed to ETS at home had significantly higher median levels of creatinine adjusted urinary cotinine than those reporting they were not exposed at home (4.19 µg/g versus 2.9 µg/g, p = 0.0039). CONCLUSIONS: Despite additional restrictions on smoking in public places in 2012-2016, over 60% of non-smoking adults in Israel continue to be exposed to ETS. Urinary cotinine levels in non-smokers have not decreased compared to 2011. Results indicate higher exposure to ETS in Arab study participants and those reporting ETS exposure at home. There is an urgent need: (1) to increase enforcement on the ban on smoking in work and public places; (2) for public health educational programs and campaigns about the adverse health effects of ETS; and (3) to develop and disseminate effective interventions to promote smoke free homes. Periodic surveys using objective measures of ETS exposure (cotinine) are an important tool for monitoring progress, or lack thereof, of policies to reduce exposure to tobacco smoke in non-smokers.

Erratum to: The burden of smoking in Israel-attributable mortality and costs (2014).

[This corrects the article DOI: 10.1186/2045-4015-3-28.].

The burden of smoking in Israel-attributable mortality and costs (2014).

BACKGROUND: Tobacco use is the single most preventable cause of death, incurring huge resource costs in terms of treating morbidity and lost productivity. This paper estimates smoking attributable mortality (SAM) as health costs in 2014 in Israel. METHODS: Longitudinal data on prevalence of smokers and ex-smokers were combined with diagnostic and gender specific data on Relative Risks (RR) to gender and disease specific population attributable risks (PAR). PAR was then applied to mortality and hospitalization data from 2011, adjusted by population growth to 2014 to calculate SAM and hospitalization days (SAHD) caused by active smoking. These were used as a base for calculating deaths, hospital days and costs attributable to passive smoking, smoking by pregnant women, residential fires and productivity losses based on international literature. RESULTS: The lagged model estimated active SAM in Israel in 2014 to be 7,025 deaths. Cardio-vascular causes accounted for 45.0% of SAM, malignant neoplasms (39.2%) and respiratory diseases (15.5%). Lung cancer alone accounted for 24.1% of SAM. There were an estimated 793, 17 and 12 deaths from passive smoking, mothers-to-be smoking and residential fires. Total SAM is around 7,847 deaths (95% CI 7,698-7,997) in 2014. We estimated 319,231 active SAHD days (95% CI 313,135-325,326). Respiratory care accounted for around one-half of active SAHD (50.5%). Cardio-Vascular causes for 33.5% and malignant neoplasms (13.2%). Lung cancer only for 4.6%. Total SAHD was around 356,601 days including 36,049 days from passive smoking. Estimated direct acute care costs of 356,601 days in a general hospital amount to around 849 (95% CI 832-865) million NIS ($244 million). Non acute care costs amount to an additional 830 million NIS ($238 million). The total health service costs amount to 1,678 million NIS (95% CI 1,646-1,710) or $482 million, 0.2% of GNP. Productivity losses account for a further 1,909 million NIS ($548 million), giving an overall smoking related cost of 3,587 million NIS (95% CI 3,519-3,656) or $1,030 million, 0.41% of GNP). CONCLUSIONS: Smoking causes a considerable burden in Israel, both in terms of the expected 7,847 lives lost and the financial costs of around 3.6 million NIS ($1,030 million or 0.42% of GNP).