Saliva Proteins of Vector Culicoides Modify Structure and Infectivity of Bluetongue Virus Particles

Bluetongue virus (BTV) and epizootic haemorrhagic disease virus (EHDV) are related orbiviruses, transmitted between their ruminant hosts primarily by certain haematophagous midge vectors (Culicoides spp.). The larger of the BTV outer-capsid proteins, ‘VP2’, can be cleaved by proteases (including trypsin or chymotrypsin), forming infectious subviral particles (ISVP) which have enhanced infectivity for adult Culicoides, or KC cells (a cell-line derived from C. sonorensis). We demonstrate that VP2 present on purified virus particles from 3 different BTV strains can also be cleaved by treatment with saliva from adult Culicoides. The saliva proteins from C. sonorensis (a competent BTV vector), cleaved BTV-VP2 more efficiently than those from C. nubeculosus (a less competent / non-vector species). Electrophoresis and mass spectrometry identified a trypsin-like protease in C. sonorensis saliva, which was significantly reduced or absent from C. nubeculosus saliva. Incubating purified BTV-1 with C. sonorensis saliva proteins also increased their infectivity for KC cells ∼10 fold, while infectivity for BHK cells was reduced by 2–6 fold. Treatment of an ‘eastern’ strain of EHDV-2 with saliva proteins of either C. sonorensis or C. nubeculosus cleaved VP2, but a ‘western’ strain of EHDV-2 remained unmodified. These results indicate that temperature, strain of virus and protein composition of Culicoides saliva (particularly its protease content which is dependent upon vector species), can all play a significant role in the efficiency of VP2 cleavage, influencing virus infectivity. Saliva of several other arthropod species has previously been shown to increase transmission, infectivity and virulence of certain arboviruses, by modulating and/or suppressing the mammalian immune response. The findings presented here, however, demonstrate a novel mechanism by which proteases in Culicoides saliva can also directly modify the orbivirus particle structure, leading to increased infectivity specifically for Culicoides cells and, in turn, efficiency of transmission to the insect vector

Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721

The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013

BACKGROUND: With recent improvements in vaccines and treatments against viral hepatitis, an improved understanding of the burden of viral hepatitis is needed to inform global intervention strategies. We used data from the Global Burden of Disease (GBD) Study to estimate morbidity and mortality for acute viral hepatitis, and for cirrhosis and liver cancer caused by viral hepatitis, by age, sex, and country from 1990 to 2013. METHODS: We estimated mortality using natural history models for acute hepatitis infections and GBD's cause-of-death ensemble model for cirrhosis and liver cancer. We used meta-regression to estimate total cirrhosis and total liver cancer prevalence, as well as the proportion of cirrhosis and liver cancer attributable to each cause. We then estimated cause-specific prevalence as the product of the total prevalence and the proportion attributable to a specific cause. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs). FINDINGS: Between 1990 and 2013, global viral hepatitis deaths increased from 0·89 million (95% uncertainty interval [UI] 0·86–0·94) to 1·45 million (1·38–1·54); YLLs from 31·0 million (29·6–32·6) to 41·6 million (39·1–44·7); YLDs from 0·65 million (0·45–0·89) to 0·87 million (0·61–1·18); and DALYs from 31·7 million (30·2–33·3) to 42·5 million (39·9–45·6). In 2013, viral hepatitis was the seventh (95% UI seventh to eighth) leading cause of death worldwide, compared with tenth (tenth to 12th) in 1990. INTERPRETATION: Viral hepatitis is a leading cause of death and disability worldwide. Unlike most communicable diseases, the absolute burden and relative rank of viral hepatitis increased between 1990 and 2013. The enormous health loss attributable to viral hepatitis, and the availability of effective vaccines and treatments, suggests an important opportunity to improve public health. FUNDING: Bill & Melinda Gates Foundation

Predicting the seasonal evolution of southern African summer precipitation in the DePreSys3 prediction system

We assess the ability of the DePreSys3 prediction system to predict austral summer precipitation (DJF) over southern Africa, defined as the African continent south of 15°S. DePresys3 is a high resolution prediction system (at a horizontal resolution of ~ 60 km in the atmosphere in mid-latitudes and of the quarter degree in the Ocean) and spans the long period 1959–2016. We find skill in predicting interannual precipitation variability, relative to a long-term trend; the anomaly correlation skill score over southern Africa is greater than 0.45 for the first summer (i.e. lead month 2–4), and 0.37 over Mozambique, Zimbabwe and Zambia for the second summer (i.e. lead month 14–16). The skill is related to the successful prediction of the El-Nino Southern Oscillation (ENSO), and the successful simulation of ENSO teleconnections to southern Africa. However, overall skill is sensitive to the inclusion of strong La-Nina events and also appears to change with forecast epoch. For example, the skill in predicting precipitation over Mozambique is significantly larger for the first summer in the 1990–2016 period, compared to the 1959–1985 period. The difference in skill in predicting interannual precipitation variability over southern Africa in different epochs is consistent with a change in the strength of the observed teleconnections of ENSO. After 1990, and consistent with the increased skill, the observed impact of ENSO appears to strengthen over west Mozambique, in association with changes in ENSO related atmospheric convergence anomalies. However, these apparent changes in teleconnections are not captured by the ensemble-mean predictions using DePreSys3. The changes in the ENSO teleconnection are consistent with a warming over the Indian Ocean and modulation of ENSO properties between the different epochs, but may also be associated with unpredictable atmospheric variability

The global burden of cancer 2013 global burden of disease cancer collaboration

Importance Cancer is among the leading causes of death worldwide. Current estimates of cancer burden in individual countries and regions are necessary to inform local cancer control strategies. Objective To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 28 cancers in 188 countries by sex from 1990 to 2013. Evidence Review The general methodology of the Global Burden of Disease (GBD) 2013 study was used. Cancer registries were the source for cancer incidence data as well as mortality incidence (MI) ratios. Sources for cause of death data include vital registration system data, verbal autopsy studies, and other sources. The MI ratios were used to transform incidence data to mortality estimates and cause of death estimates to incidence estimates. Cancer prevalence was estimated using MI ratios as surrogates for survival data; YLDs were calculated by multiplying prevalence estimates with disability weights, which were derived from population-based surveys; YLLs were computed by multiplying the number of estimated cancer deaths at each age with a reference life expectancy; and DALYs were calculated as the sum of YLDs and YLLs. Findings In 2013 there were 14.9 million incident cancer cases, 8.2 million deaths, and 196.3 million DALYs. Prostate cancer was the leading cause for cancer incidence (1.4 million) for men and breast cancer for women (1.8 million). Tracheal, bronchus, and lung (TBL) cancer was the leading cause for cancer death in men and women, with 1.6 million deaths. For men, TBL cancer was the leading cause of DALYs (24.9 million). For women, breast cancer was the leading cause of DALYs (13.1 million). Age-standardized incidence rates (ASIRs) per 100 000 and age-standardized death rates (ASDRs) per 100 000 for both sexes in 2013 were higher in developing vs developed countries for stomach cancer (ASIR, 17 vs 14; ASDR, 15 vs 11), liver cancer (ASIR, 15 vs 7; ASDR, 16 vs 7), esophageal cancer (ASIR, 9 vs 4; ASDR, 9 vs 4), cervical cancer (ASIR, 8 vs 5; ASDR, 4 vs 2), lip and oral cavity cancer (ASIR, 7 vs 6; ASDR, 2 vs 2), and nasopharyngeal cancer (ASIR, 1.5 vs 0.4; ASDR, 1.2 vs 0.3). Between 1990 and 2013, ASIRs for all cancers combined (except nonmelanoma skin cancer and Kaposi sarcoma) increased by more than 10% in 113 countries and decreased by more than 10% in 12 of 188 countries. Conclusions and Relevance Cancer poses a major threat to public health worldwide, and incidence rates have increased in most countries since 1990. The trend is a particular threat to developing nations with health systems that are ill-equipped to deal with complex and expensive cancer treatments. The annual update on the Global Burden of Cancer will provide all stakeholders with timely estimates to guide policy efforts in cancer prevention, screening, treatment, and palliation

Five insights from the Global Burden of Disease Study 2019

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3.5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.Peer reviewe

BRCA1 effects on the cell cycle and the DNA damage response are linked to altered gene expression.

The breast and ovarian cancer susceptibility gene product BRCA1 has been reported to be expressed in a cell cycle-dependent manner; possess transcriptional activity; associate with several proteins, including the p53 tumor suppressor; and play an integral role in certain types of DNA repair. We show here that ectopic expression of BRCA1 using an adenovirus vector (Ad-BRCA1) leads to dephosphorylation of the retinoblastoma protein accompanied by a decrease in cyclin-dependent kinase activity. Flow cytometric analysis on Ad-BRCA1-infected cells revealed a G(1) or G(2) phase accumulation. High density cDNA array screening of colon, lung, and breast cancer cells identified several genes affected by BRCA1 expression in a p53-independent manner, including DNA damage response genes and genes involved in cell cycle control. Notable changes included induction of the GADD45 and GADD153 genes and a reduction in cyclin B1 expression. Therefore, BRCA1 has the potential to modulate the expression of genes and function of proteins involved in cell cycle control and DNA damage response pathways

ECG waveform analysis in intrapartum fetal monitoring

Australian and New Zealand Journal of Obstetrics and Gynaecology33139-44AZOG

The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013

Background: With recent improvements in vaccines and treatments against viral hepatitis, a better understanding of the burden of viral hepatitis is needed to inform global intervention strategies. We present estimates from the Global Burden of Disease (GBD) Study of morbidity and mortality for acute viral hepatitis, and for cirrhosis and liver cancer due to viral hepatitis by age, sex and country for 1990 through 2013. Methods: Mortality was estimated using natural history models for acute hepatitis and GBD’s cause-of-death ensemble model for cirrhosis and liver cancer. We estimated disease prevalence, and liver cancer and cirrhosis aetiologies via meta-regression. Disability adjusted life-years (DALYs) were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs). Findings: Between 1990 and 2013, viral hepatitis deaths increased from 0·90 million (95% uncertainty interval 0·86 – 0·94) to 1·45 million (1·38–1·54); YLLs increased from 31·0 million (29·6–32·6) to 41·6 million (39·1–44·7); YLDs, from 0·65 million (0·45–0·89) to 0·87 million (0·61–1·18); and DALYs, from 31·7 million (30·2– 33·3) to 42·5 million (39·9–45·6). In 2013, viral hepatitis was the 7th leading cause of death globally. Interpretation: Viral hepatitis is a leading cause of death and disability worldwide. Unlike most communicable diseases, between 1990 and 2013, viral hepatitis has increased in terms of both absolute burden and its relative rank