Background. Chronic alcohol-related liver disease (ALD) is mediated by insulin resistance, mitochondrial dysfunction, inflammation, oxidative stress, and DNA damage. Recent studies suggest that dysregulated lipid metabolism with accumulation of ceramides, together with ER stress potentiate hepatic insulin resistance and may cause steatohepatitis to progress.Objective. We examined the degree to which hepatic insulin resistance in advanced human ALD is correlated with ER stress, dysregulated lipid metabolism, and ceramide accumulation.Methods. We assessed the integrity of insulin signaling through the Akt pathway and measured proceramide and ER stress gene expression, ER stress signaling proteins, and ceramide profiles in liver tissue.Results. Chronic ALD was associated with increased expression of insulin, IGF-1, and IGF-2 receptors, impaired signaling through IGF-1R and IRS1, increased expression of multiple proceramide and ER stress genes and proteins, and higher levels of the C14, C16, C18, and C20 ceramide species relative to control.Conclusions. In human chronic ALD, persistent hepatic insulin resistance is associated with dysregulated lipid metabolism, ceramide accumulation, and striking upregulation of multiple ER stress signaling molecules. Given the role of ceramides as mediators of ER stress and insulin resistance, treatment with ceramide enzyme inhibitors may help reverse or halt progression of chronic ALD.

In the midst of global biodiversity loss and rising disease incidence in wildlife, there has been growing interest in the role of infectious disease in species extinction. At local scales infectious disease is a common driver of population declines but globally it is an infrequent driver of species extinction and endangerment. For those unfortunate species threatened by disease questions remain, including when, along the pathway to extinction, do pathogens become a threat? We used the 2011 IUCN Red List, focusing on amphibians, birds, and mammals to test the null hypothesis that the proportion of species threatened by disease is the same in each status category (least concern to extinct). Overall, we found that pathogens appear to increase in importance as species move towards extinction though this varies with host taxonomy. We compare this finding to other threats (e.g. land-use change and invasive species) and discuss the role of potential ecological and artifactual drivers. Furthermore, we identify what other threats most frequently co-occur with infectious disease to examine the specific role of disease in driving extinction. We determined that infectious disease is rarely the sole driver of extinction and that being affected by other threats increases the odds of infectious disease co-occurring as a driver of extinction. Ultimately, our conclusions echo previous calls for baseline data on the presence of pathogens in species when they show the first signs of extinction risk and arguably before.

85.8% referred to White/Caucasians, 9.70% to Black/African Americans, 3.16% to Asian, 0.633% to Hispanics, and 0.633% to Native Americans. No cases referred to Native Hawaiians/Pacific Islanders. The proportion of mentions of race/ethnicity classified as either a routine descriptor or central to the case varied by racial/ethnic category. The association between genetics and disease in cases also varied by racial/ethnic category. Insights. The routinized use of race/ethnicity with no specific goal in preparation materials, such as question banks, risks contributing to racial bias. The implications of routinized use extend to assessment in medical education. Race/ethnicity should be used only when referring to social experiences of groups relevant to their health, not as a proxy for genetics, social class, or culture.