Alcohol use disorder and the gut

Acute and chronic gastrointestinal problems are common in the setting of excessive alcohol use, and excessive alcohol use is associated with injury to all parts of the gastrointestinal tract. There is mounting evidence of gastrointestinal injury and increased cancer risk even from moderate alcohol consumption. The major causes of alcohol-related morbidity and mortality within the gastrointestinal system are liver disease, pancreatitis and gastrointestinal cancer. Other alcohol-related intestinal dysfunction is common but not life-threatening, leading to diarrhoea, malabsorption and nutritional deficiencies. This review describes non-neoplastic and neoplastic alcohol-related disorders of the gastrointestinal tract, omitting the liver, which has been reviewed elsewhere.     

Interrelationships between Cellular Density,Mosaic Patterning,and Dendritic Coverage of VGluT3 Amacrine Cells

Amacrine cells of the retina are conspicuously variable in their morphologies, their population demographics, and their ensuing functions. Vesicular glutamate transporter 3 (VGluT3) amacrine cells are a recently characterized type of amacrine cell exhibiting local dendritic autonomy. The present analysis has examined three features of this VGluT3 population, including their density, local distribution, and dendritic spread, to discern the extent to which these are interrelated, using male and female mice. We first demonstrate that Bax-mediated cell death transforms the mosaic of VGluT3 cells from a random distribution into a regular mosaic. We subsequently examine the relationship between cell density and mosaic regularity across recombinant inbred strains of mice, finding that, although both traits vary across the strains, they exhibit minimal covariation. Other genetic determinants must therefore contribute independently to final cell number and to mosaic order. Using a conditional KO approach, we further demonstrate that Bax acts via the bipolar cell population, rather than cell-intrinsically, to control VGluT3 cell number. Finally, we consider the relationship between the dendritic arbors of single VGluT3 cells and the distribution of their homotypic neighbors. Dendritic field area was found to be independent of Voronoi domain area, while dendritic coverage of single cells was not conserved, simply increasing with the size of the dendritic field. Bax-KO retinas exhibited a threefold increase in dendritic coverage. Each cell, however, contributed less dendrites at each depth within the plexus, intermingling their processes with those of neighboring cells to approximate a constant volumetric density, yielding a uniformity in process coverage across the population.SIGNIFICANCE STATEMENT Different types of retinal neuron spread their processes across the surface of the retina to achieve a degree of dendritic coverage that is characteristic of each type. Many of these types achieve a constant coverage by varying their dendritic field area inversely with the local density of like-type neighbors. Here we report a population of retinal amacrine cells that do not develop dendritic arbors in relation to the spatial positioning of such homotypic neighbors; rather, this cell type modulates the extent of its dendritic branching when faced with a variable number of overlapping dendritic fields to approximate a uniformity in dendritic density across the retina.     

SALAD‐BAAR: A numerical risk score for hospital admission or emergency department presentation in ambulatory patients with cardiovascular disease

BackgroundWhile many interventions to reduce hospital admissions and emergency department (ED) visits for patients with cardiovascular disease have been developed, identifying ambulatory cardiac patients at high risk for admission can be challenging.HypothesisA computational model based on readily accessible clinical data can identify patients at risk for admission.MethodsElectronic health record (EHR) data from a tertiary referral center were used to generate decision tree and logistic regression models. International Classification of Disease (ICD) codes, labs, admissions, medications, vital signs, and socioenvironmental variables were used to model risk for ED presentation or hospital admission within 90 days following a cardiology clinic visit. Model training and testing were performed with a 70:30 data split. The final model was then prospectively validated.ResultsA total of 9326 patients and 46 465 clinic visits were analyzed. A decision tree model using 75 patient characteristics achieved an area under the curve (AUC) of 0.75 and a logistic regression model achieved an AUC of 0.73. A simplified 9‐feature model based on logistic regression odds ratios achieved an AUC of 0.72. A further simplified numerical score assigning 1 or 2 points to each variable achieved an AUC of 0.66, specificity of 0.75, and sensitivity of 0.58. Prospectively, this final model maintained its predictive performance (AUC 0.63–0.60).ConclusionNine patient characteristics from routine EHR data can be used to inform a highly specific model for hospital admission or ED presentation in cardiac patients. This model can be simplified to a risk score that is easily calculated and retains predictive performance.