Prediction Model for 30-day Outcomes Among Emergency Department Patients with Lower Gastrointestinal Bleeding

Introduction: There are currently no robust tools available for risk stratification of emergency department (ED) patients with lower gastrointestinal bleed (LGIB). Our aim was to identify risk factors and develop a preliminary model to predict 30-day serious adverse events among ED LGIB patients.Methods: We conducted a health records review including adult ED patients with acute LGIB. We used a composite outcome of 30-day all-cause death, recurrent LGIB, need for intervention to control the bleeding, and severe adverse events resulting in intensive care unit admission. One researcher collected data for variables and a second researcher independently collected 10% of the variables for inter-observer reliability. We used backward multivariable logistic regression analysis and SELECTION=SCORE option to create a preliminary risk-stratification tool. We assessed the diagnostic accuracy of the final model.Results: Of 372 patients, 48 experienced an adverse outcome. We found that age ≥75 years, hemoglobin ≤100 g/L, international normalized ratio ≥2.0, ongoing bleed in the ED, and a medical history of colorectal polyps were statistically significant predictors in the multivariable regression analysis. The area under the curve (AUC) for the model was 0.83 (95% confidence interval, 0.77-0.89). We developed a scoring system based on the logistic regression model and found a sensitivity 0.96 (0.90-1.00) and specificity 0.53 (0.48-0.59) for a cut-off score of 1.Conclusion: This model showed good ability to differentiate patients with and without serious outcomes as evidenced by the high AUC and sensitivity. The results of this study could be used in the prospective derivation of a clinical decision tool

Foldamers of β-peptides : conformational preference of peptides formed by rigid building blocks : The first MI-IR spectra of a triamide nanosystem

To determine local chirality driven conformational preferences of small aminocyclobutane-1-carboxylic acid derivatives, X-(ACBA) n -Y, their matrix-isolation IR spectra were recorded and analyzed. For the very first time model systems of this kind were deposited in a frozen (~10 K) noble gas matrix to reduce line width and thus, the recorded sharp vibrational lines were analyzed in details. For cis-(S,R)-1 monomer two “zigzag” conformers composed of either a six or an eight-membered H-bonded pseudo ring was identified. For trans-(S,S)-2 stereoisomer a zigzag of an eight-membered pseudo ring and a helical building unit were determined. Both findings are fully consistent with our computational results, even though the relative conformational ratios were found to vary with respect to measurements. For the dimers (S,R,S,S)-3 and (S,S,S,R)-4 as many as four different cis,trans and three different trans,cis conformers were localized in their matrix-isolation IR (MI-IR) spectra. These foldamers not only agree with the previous computational and NMR results, but also unambiguously show for the first time the presence of a structure made of a cis,trans conformer which links a “zigzag” and a helical foldamer via a bifurcated H-bond. The present work underlines the importance of MI-IR spectroscopy, applied for the first time for triamides to analyze the conformational pool of small biomolecules. We have shown that the local chirality of a β-amino acid can fully control its backbone folding preferences. Unlike proteogenic α-peptides, β- and especially (ACBA) n type oligopeptides could thus be used to rationally design and influence foldamer’s structural preferences

Modulation of the endocannabinoids N-Arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) on Executive Functions in Humans

Animal studies point to an implication of the endocannabinoid system on executive functions. In humans, several studies have suggested an association between acute or chronic use of exogenous cannabinoids (Δ9-tetrahydrocannabinol) and executive impairments. However, to date, no published reports establish the relationship between endocannabinoids, as biomarkers of the cannabinoid neurotransmission system, and executive functioning in humans. The aim of the present study was to explore the association between circulating levels of plasma endocannabinoids N-arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) and executive functions (decision making, response inhibition and cognitive flexibility) in healthy subjects. One hundred and fifty seven subjects were included and assessed with the Wisconsin Card Sorting Test; Stroop Color and Word Test; and Iowa Gambling Task. All participants were female, aged between 18 and 60 years and spoke Spanish as their first language. Results showed a negative correlation between 2-AG and cognitive flexibility performance (r = −.37; p<.05). A positive correlation was found between AEA concentrations and both cognitive flexibility (r = .59; p<.05) and decision making performance (r = .23; P<.05). There was no significant correlation between either 2-AG (r = −.17) or AEA (r = −.08) concentrations and inhibition response. These results show, in humans, a relevant modulation of the endocannabinoid system on prefrontal-dependent cognitive functioning. The present study might have significant implications for the underlying executive alterations described in some psychiatric disorders currently associated with endocannabinoids deregulation (namely drug abuse/dependence, depression, obesity and eating disorders). Understanding the neurobiology of their dysexecutive profile might certainly contribute to the development of new treatments and pharmacological approaches

The human keratins: biology and pathology

The keratins are the typical intermediate filament proteins of epithelia, showing an outstanding degree of molecular diversity. Heteropolymeric filaments are formed by pairing of type I and type II molecules. In humans 54 functional keratin genes exist. They are expressed in highly specific patterns related to the epithelial type and stage of cellular differentiation. About half of all keratins—including numerous keratins characterized only recently—are restricted to the various compartments of hair follicles. As part of the epithelial cytoskeleton, keratins are important for the mechanical stability and integrity of epithelial cells and tissues. Moreover, some keratins also have regulatory functions and are involved in intracellular signaling pathways, e.g. protection from stress, wound healing, and apoptosis. Applying the new consensus nomenclature, this article summarizes, for all human keratins, their cell type and tissue distribution and their functional significance in relation to transgenic mouse models and human hereditary keratin diseases. Furthermore, since keratins also exhibit characteristic expression patterns in human tumors, several of them (notably K5, K7, K8/K18, K19, and K20) have great importance in immunohistochemical tumor diagnosis of carcinomas, in particular of unclear metastases and in precise classification and subtyping. Future research might open further fields of clinical application for this remarkable protein family

Prediction Model for 30-day Outcomes Among Emergency Department Patients with Lower Gastrointestinal Bleeding

Introduction: There are currently no robust tools available for risk stratification of emergency department (ED) patients with lower gastrointestinal bleed (LGIB). Our aim was to identify risk factors and develop a preliminary model to predict 30-day serious adverse events among ED LGIB patients.Methods: We conducted a health records review including adult ED patients with acute LGIB. We used a composite outcome of 30-day all-cause death, recurrent LGIB, need for intervention to control the bleeding, and severe adverse events resulting in intensive care unit admission. One researcher collected data for variables and a second researcher independently collected 10% of the variables for inter-observer reliability. We used backward multivariable logistic regression analysis and SELECTION=SCORE option to create a preliminary risk-stratification tool. We assessed the diagnostic accuracy of the final model.Results: Of 372 patients, 48 experienced an adverse outcome. We found that age ≥75 years, hemoglobin ≤100 g/L, international normalized ratio ≥2.0, ongoing bleed in the ED, and a medical history of colorectal polyps were statistically significant predictors in the multivariable regression analysis. The area under the curve (AUC) for the model was 0.83 (95% confidence interval, 0.77-0.89). We developed a scoring system based on the logistic regression model and found a sensitivity 0.96 (0.90-1.00) and specificity 0.53 (0.48-0.59) for a cut-off score of 1.Conclusion: This model showed good ability to differentiate patients with and without serious outcomes as evidenced by the high AUC and sensitivity. The results of this study could be used in the prospective derivation of a clinical decision tool

An experimental study of catechol-o-methyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition

Observational studies have suggested that psychometric psychosis liability and a functional polymorphism in the catechol-O-methyltransferase (COMT Val(158)Met) gene moderate the psychosis-inducing effect of cannabis. To replicate and extend this finding, a double-blind, placebo-controlled cross-over design was used in which patients with a psychotic disorder (n = 30), relatives of patients with a psychotic disorder (n = 12), and healthy controls (n = 32) were exposed to D-9-tetrahydrocannabinol (D-9-THC, the principal component of cannabis) or placebo, followed by cognitive assessment and assessment of current psychotic experiences. Previous expression of psychometric psychosis liability was also assessed. Models of current psychotic experiences and cognition were examined with multilevel random regression analyses to assess (i) main effects of genotype and condition, (ii) interactions between condition and genotype, and (iii) three-way interactions between condition, genotype, and psychometric psychosis liability. Carriers of the Val allele were most sensitive to D-9-THC-induced psychotic experiences, but this was conditional on prior evidence of psychometric psychosis liability. D-9-THC impacted negatively on cognitive measures. Carriers of the Val allele were also more sensitive to D-9-THC-induced memory and attention impairments compared to carriers of the Met allele. Experimental effects of D-9-THC on cognition and psychosis are moderated by COMT Val 158 Met genotype, but the effects may in part be conditional on the additional presence of pre-existing psychosis liability. The association between cannabis and psychosis may represent higher order gene-environment and gene-gene interactions