The Emergency Medicine Specimen Bank: An Innovative Approach To Biobanking In Acute Care

The Emergency Medicine Specimen Bank (EMSB) was developed to facilitate precision medicine in acute care. The EMSB is a biorepository of clinical health data and biospecimens collected from all adult English‐ or Spanish‐speaking individuals who are able and willing to provide consent and are treated at the UCHealth–University of Colorado Hospital Emergency Department. The EMSB is the first acute care biobank that seeks to enroll all patients, with all conditions who present to the ED. Acute care biobanking presents many challenges that are unique to acute care settings such as providing informed consent in a uniquely stressful and fast‐paced environment and collecting, processing, and storing samples for tens of thousands of patients per year. Here, we describe the process by which the EMSB overcame these challenges and was integrated into clinical workflow allowing for operation 24 hours a day, 7 days a week at a reasonable cost. Other institutions can implement this template, further increasing the power of biobanking research to inform treatment strategies and interventions for common and uncommon phenotypes in acute care settings.     

Cardiac performance and myocardial blood flow in pigs with compensated right ventricular hypertrophy

Compensated right ventricular hypertrophy (RVH), defined by a greater than 100% RV weight increase compared to 17 normal animals, was created in 17 young pigs by pulmonary arterial banding. RVH was associated with significant elevations (p less than 0.001) in RV peak dP/dt, RV stroke work, RV minute work and RV rate-pressure product compared to normal animals matched by body weight. RV peak dP/dt showed a positive correlation (p less than 0.001) with RV peak systolic pressure in normals; however, this relationship was lost in banded animals since progressively higher RV pressures were not associated with concomitant increases in RV peak dP/dt, thus, suggesting an intrinsic difference between right and left ventricles when working at systemic arterial pressures. Time to RV peak dP/dt became progressively longer (p less than 0.05) as RV weight increased in the RVH animals. When indices of cardiac work were normalized for RV weight, the RVH group could not be distinguished from normals suggesting that the performance per unit weight of RV muscle in RVH was unchanged. Total RV blood flow, measured by radioactive microspheres, closely followed (p less than 0.001) increases in RV mass in banded animals. Blood flow . g-1 muscle in RV and septal right side were unaltered in RVH; however, regional perfusion of the left ventricle (p less than 0.001) and septal right side were unaltered in RVH; however, regional perfusion of the left ventricle (p less than 0.001) and septal left side (p less than 0.02) increased significantly. There were regional variations in RV perfusion which were maintained in compensated RVH; stress (isoprenaline infusion) caused significant increases in blood flow to all regions of the heart in normal and RVH animals (p less than 0.001), but relative regional distribution was maintained. Our observations suggest a relationship between myocardial work and blood flow in RVH such that RV perfusion . g-1 is elevated to meet haemodynamic requirements once RV regional work . g-1 become greater than normal.     

Interspecies comparison of stellate cell‐containing macula flavae and vitamin A storage in vocal fold mucosa

The macula flavae (MF), populated by vitamin A‐storing stellate cells (SCs), are believed to play a fundamental role in development, maintenance and repair of the vocal fold (VF) mucosa; however, to date, they have mostly been examined in observational human cadaver studies. Here, we conducted an interspecies comparison of MF and SC phenotype, as well as vitamin A quantification and localization, in human, pig, dog, rabbit and rat VF mucosae. MF containing vitamin A‐positive SCs were only identified in human and rat specimens. Pig, dog and rabbit VF mucosae contained no discernable MF, but rather exhibited preferential vitamin A localization to mucous (pig), serous (dog) or mixed (rabbit) glands. This glandular vitamin A storage corresponded to exceedingly high concentrations of retinol in pig and dog mucosae, and retinyl ester in dog mucosa. These findings have significant implications for the presumed role of the MF and SCs in VF biology, the nature of vitamin A storage within the VF mucosa, and the selection of an appropriate animal model for future experimental studies.     

Differential expression of cannabinoid receptors in the human colon: cannabinoids promote epithelial wound healing

BACKGROUND & AIMS: Two G-protein-coupled cannabinoid receptors, termed CB1 and CB2, have been identified and several mammalian enteric nervous systems express CB1 receptors and produce endocannabinoids. An immunomodulatory role for the endocannabinoid system in gastrointestinal inflammatory disorders has been proposed and this study sought to determine the location of both cannabinoid receptors in human colon and to investigate epithelial receptor function. METHODS: The location of CB1 and CB2 receptors in human colonic tissue was determined by immunohistochemistry. Primary colonic epithelial cells were treated with both synthetic and endogenous cannabinoids in vitro, and biochemical coupling of the receptors to known signaling events was determined by immunoblotting. Human colonic epithelial cell lines were used in cannabinoid-binding studies and as a model for in vitro wound-healing experiments. RESULTS: CB1-receptor immunoreactivity was evident in normal colonic epithelium, smooth muscle, and the submucosal myenteric plexus. CB1- and CB2-receptor expression was present on plasma cells in the lamina propria, whereas only CB2 was present on macrophages. CB2 immunoreactivity was seen in the epithelium of colonic tissue characteristic of inflammatory bowel disease. Cannabinoids enhanced epithelial wound closure either alone or in combination with lysophosphatidic acid through a CB1-lysophosphatidic acid 1 heteromeric receptor complex. CONCLUSIONS: CB1 receptors are expressed in normal human colon and colonic epithelium is responsive biochemically and functionally to cannabinoids. Increased epithelial CB2-receptor expression in human inflammatory bowel disease tissue implies an immunomodulatory role that may impact on mucosal immunity.     

Schizophrenia: A Concise Overview of Incidence, Prevalence, and Mortality

Recent systematic reviews have encouraged the psychiatric researchcommunity to reevaluate the contours of schizophrenia epidemiology.This paper provides a concise overview of three related systematicreviews on the incidence, prevalence, and mortality associatedwith schizophrenia. The reviews shared key methodological featuresregarding search strategies, analysis of the distribution ofthe frequency estimates, and exploration of the influence ofkey variables (sex, migrant status, urbanicity, secular trend,economic status, and latitude). Contrary to previous interpretations,the incidence of schizophrenia shows prominent variation betweensites. The median incidence of schizophrenia was 15.2/100,000persons, and the central 80% of estimates varied over a fivefoldrange (7.7–43.0/100,000). The rate ratio for males:femaleswas 1.4:1. Prevalence estimates also show prominent variation.The median lifetime morbid risk for schizophrenia was 7.2/1,000persons. On the basis of the standardized mortality ratio, peoplewith schizophrenia have a two- to threefold increased risk ofdying (median standardized mortality ratio = 2.6 for all-causemortality), and this differential gap in mortality has increasedover recent decades. Compared with native-born individuals,migrants have an increased incidence and prevalence of schizophrenia.Exposures related to urbanicity, economic status, and latitudeare also associated with various frequency measures. In conclusion,the epidemiology of schizophrenia is characterized by prominentvariability and gradients that can help guide future research. incidence • mortality • prevalence • review • schizophrenia     

Isolation of C15: a novel antibody generated by phage display against mesenchymal stem cell-enriched fractions of adult human marrow

Adult bone marrow stroma contains a source of mesenchymal stem cells (MSC) that have the capacity to self-renew and differentiate into multiple stromal lineages. These rare cells can be visualised indirectly by the formation of heterogeneous colonies, containing stem cells and their differentiated progeny in long-term culture. If MSC and their associated progenitor and precursor populations are to reach their full therapeutic potential, markers will be required to identify and characterize specific bone marrow stromal subsets. We sought to use phage display to generate antibodies against bone marrow mononuclear cells (BMMNC) enriched for colony forming cells. Initially, we identified our target cell population by comparing the colony forming efficiency (CFE) of CD49a-positive, STRO-1-positive and CD45-negative BMMNC subpopulations with unseparated BMMNC. Selection with anti-CD49a gave the greatest enrichment (19-fold) of colony forming cells and in light of these findings, we generated phage antibodies against CD49a-positive BMMNC by simultaneous positive/negative selection. A dominant clone (C15), generated after 3 rounds of selection, has been isolated and sequenced, then characterized for cell and tissue specificity. Sequence analysis showed that the V(H) and V(L) gene segments of C15 aligned most closely to the VH26/DP-47 and IGLV3S1/DPL16 germline V segments found in the synthetic repertoire. C15 bound to 4% of freshly isolated BMMNC and localized to osteoblastic cells and proximal marrow cells in areas of active bone formation in sections of osteophyte. C15 binding was upregulated in cultured bone marrow stromal cells (BMSC) and was also detected on bone-derived cell lines. This report demonstrates that phage display is a powerful tool for the isolation of antibodies against rare cell populations, and provides a platform for the future application of this technology in the search for antigens on MSC and other rare cell populations.