Inherited liver shunts in dogs elucidate pathways regulating embryonic development and clinical disorders of the portal vein

Congenital disorders of the hepatic portal vasculature are rare in man but occur frequently in certain dog breeds. In dogs, there are two main subtypes: intrahepatic portosystemic shunts, which are considered to stem from defective closure of the embryonic ductus venosus, and extrahepatic shunts, which connect the splanchnic vascular system with the vena cava or vena azygos. Both subtypes result in nearly complete bypass of the liver by the portal blood flow. In both subtypes the development of the smaller branches of the portal vein tree in the liver is impaired and terminal branches delivering portal blood to the liver lobules are often lacking. The clinical signs are due to poor liver growth, development, and function. Patency of the ductus venosus seems to be a digenic trait in Irish wolfhounds, whereas Cairn terriers with extrahepatic portosystemic shunts display a more complex inheritance. The genes involved in these disorders cannot be identified with the sporadic human cases, but in dogs, the genome-wide study of the extrahepatic form is at an advanced stage. The canine disease may lead to the identification of novel genes and pathways cooperating in growth and development of the hepatic portal vein tree. The same pathways likely regulate the development of the vascular system of regenerating livers during liver diseases such as hepatitis and cirrhosis. Therefore, the identification of these molecular pathways may provide a basis for future proregenerative intervention

The burden of diseases, injuries, and risk factors by state in the USA, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides a comprehensive assessment of health and risk factor trends at global, regional, national, and subnational levels. This study aims to examine the burden of diseases, injuries, and risk factors in the USA and highlight the disparities in health outcomes across different states. Methods: GBD 2021 analysed trends in mortality, morbidity, and disability for 371 diseases and injuries and 88 risk factors in the USA between 1990 and 2021. We used several metrics to report sources of health and health loss related to specific diseases, injuries, and risk factors. GBD 2021 methods accounted for differences in data sources and biases. The analysis of levels and trends for causes and risk factors within the same computational framework enabled comparisons across states, years, age groups, and sex. GBD 2021 estimated years lived with disability (YLDs) and disability-adjusted life-years (DALYs; the sum of years of life lost to premature mortality and YLDs) for 371 diseases and injuries, years of life lost (YLLs) and mortality for 288 causes of death, and life expectancy and healthy life expectancy (HALE). We provided estimates for 88 risk factors in relation to 155 health outcomes for 631 risk–outcome pairs and produced risk-specific estimates of summary exposure value, relative health risk, population attributable fraction, and risk-attributable burden measured in DALYs and deaths. Estimates were produced by sex (male and female), age (25 age groups from birth to ≥95 years), and year (annually between 1990 and 2021). 95% uncertainty intervals (UIs) were generated for all final estimates as the 2·5th and 97·5th percentiles values of 500 draws (ie, 500 random samples from the estimate's distribution). Uncertainty was propagated at each step of the estimation process. Findings: We found disparities in health outcomes and risk factors across US states. Our analysis of GBD 2021 highlighted the relative decline in life expectancy and HALE compared with other countries, as well as the impact of COVID-19 during the first 2 years of the pandemic. We found a decline in the USA's ranking of life expectancy from 1990 to 2021: in 1990, the USA ranked 35th of 204 countries and territories for males and 19th for females, but dropped to 46th for males and 47th for females in 2021. When comparing life expectancy in the best-performing and worst-performing US states against all 203 other countries and territories (excluding the USA as a whole), Hawaii (the best-ranked state in 1990 and 2021) dropped from sixth-highest life expectancy in the world for males and fourth for females in 1990 to 28th for males and 22nd for females in 2021. The worst-ranked state in 2021 ranked 107th for males (Mississippi) and 99th for females (West Virginia). 14 US states lost life expectancy over the study period, with West Virginia experiencing the greatest loss (2·7 years between 1990 and 2021). HALE ranking declines were even greater; in 1990, the USA was ranked 42nd for males and 32nd for females but dropped to 69th for males and 76th for females in 2021. When comparing HALE in the best-performing and worst-performing US states against all 203 other countries and territories, Hawaii ranked 14th highest HALE for males and fifth for females in 1990, dropping to 39th for males and 34th for females in 2021. In 2021, West Virginia—the lowest-ranked state that year—ranked 141st for males and 137th for females. Nationally, age-standardised mortality rates declined between 1990 and 2021 for many leading causes of death, most notably for ischaemic heart disease (56·1% [95% UI 55·1–57·2] decline), lung cancer (41·9% [39·7–44·6]), and breast cancer (40·9% [38·7–43·7]). Over the same period, age-standardised mortality rates increased for other causes, particularly drug use disorders (878·0% [770·1–1015·5]), chronic kidney disease (158·3% [149·6–167·9]), and falls (89·7% [79·8–95·8]). We found substantial variation in mortality rates between states, with Hawaii having the lowest age-standardised mortality rate (433·2 per 100 000 [380·6–493·4]) in 2021 and Mississippi having the highest (867·5 per 100 000 [772·6–975·7]). Hawaii had the lowest age-standardised mortality rates throughout the study period, whereas Washington, DC, experienced the most improvement (a 40·7% decline [33·2–47·3]). Only six countries had age-standardised rates of YLDs higher than the USA in 2021: Afghanistan, Lesotho, Liberia, Mozambique, South Africa, and the Central African Republic, largely because the impact of musculoskeletal disorders, mental disorders, and substance use disorders on age-standardised disability rates in the USA is so large. At the state level, eight US states had higher age-standardised YLD rates than any country in the world: West Virginia, Kentucky, Oklahoma, Pennsylvania, New Mexico, Ohio, Tennessee, and Arizona. Low back pain was the leading cause of YLDs in the USA in 1990 and 2021, although the age-standardised rate declined by 7·9% (1·8–13·0) from 1990. Depressive disorders (56·0% increase [48·2–64·3]) and drug use disorders (287·6% [247·9–329·8]) were the second-leading and third-leading causes of age-standardised YLDs in 2021. For females, mental health disorders had the highest age-standardised YLD rate, with an increase of 59·8% (50·6–68·5) between 1990 and 2021. Hawaii had the lowest age-standardised rates of YLDs for all sexes combined (12 085·3 per 100 000 [9090·8–15 557·1]), whereas West Virginia had the highest (14 832·9 per 100 000 [11 226·9–18 882·5]). At the national level, the leading GBD Level 2 risk factors for death for all sexes combined in 2021 were high systolic blood pressure, high fasting plasma glucose, and tobacco use. From 1990 to 2021, the age-standardised mortality rates attributable to high systolic blood pressure decreased by 47·8% (43·4–52·5) and for tobacco use by 5·1% (48·3%–54·1%), but rates increased for high fasting plasma glucose by 9·3% (0·4–18·7). The burden attributable to risk factors varied by age and sex. For example, for ages 15–49 years, the leading risk factors for death were drug use, high alcohol use, and dietary risks. By comparison, for ages 50–69 years, tobacco was the leading risk factor for death, followed by dietary risks and high BMI. Interpretation: GBD 2021 provides valuable information for policy makers, health-care professionals, and researchers in the USA at the national and state levels to prioritise interventions, allocate resources effectively, and assess the effects of health policies and programmes. By addressing socioeconomic determinants, risk behaviours, environmental influences, and health disparities among minority populations, the USA can work towards improving health outcomes so that people can live longer and healthier lives. Funding: Bill & Melinda Gates Foundation

Anti-angiogenic activities of the leaves of <i>Tapinanthus bangwensis</i> (Engl. and K. Krause) Danser Loranthaceae growing on three host trees in south-western Nigeria

AbstractThe control of angiogenic process is of immense importance to the overall health of mankind to avert out-of-control complications such as tumours and cancers. Tapinanthus bangwensis (TBG) is a semi-parasitic plant with multipurpose uses in Nigerian ethno-medicine among which is its anti-infective properties as well as the anti-tumor and restoration of damaged tissues. Despite the wide and varied uses of TBG, the anti-angiogenic investigation of the plant on different host trees is lacking while the documentation and scientific validation of indigenous knowledge on plants’ use is urgent. The present work focuses on the anti-angiogenic activities of the crude extracts and partitioned fractions of the leaves of Tapinanthus bangwensis (TBG) using the Chick chorio allantoic membrane (CAM) model. The plant was collected from three different host trees namely Albizia lebbeck (AL), Stereospermum kunthianum (SK) and Tabebuia rosea (TR). The methanolic crude extracts and solvent-partitioned fractions of TBG-SK samples were assessed for their anti-angiogenic activities using the chick chorio allantoic membrane (CAM) in ovo and in vitro assay methods respectively. Purification and isolation of major compound(s) in the chloroform fraction of TBG extract obtained from Stereospermum kunthianum host tree (TBG-SK) was carried out using chromatographic and spectroscopic methods (NMR, MS).The crude methanolic extract of TBG-SK was most potent (100% activity) in the CAM in ovo assay while the chloroform fraction produced a significantly (p&lt;0.05) highest average reduction in blood vessels with resultant formation of large avascular zones on CAM following an in vitro CAM assay. The anti-angiogenic chloroform fraction revealed the presence of a UV-active triterpenoid moiety. Findings from this work, has provided some justification for the folkloric use of TBG and thus forms a potential basis for drug discovery for wide-ranging disease states.</jats:p