Assessing lactate concentration as a predictor of 28-day in-hospital mortality in the presence of ethanol: A retrospective study of emergency department patients.

Background: Presence of ethanol (EtOH) may alter the relationship between blood lactate concentrations and mortality. This study compares lactate-associated mortality risk in the presence and absence of EtOH.

Methods: We performed a retrospective cohort study including all patients, age >17 years, presenting from January 2012-December 2018, to an urban, academic emergency department, with a clinically measured lactate.

Squamous epithelial cell presence reduces accuracy of urinalysis for prediction of positive urine cultures.

Background: Diagnostic value of urinalysis specimens contaminated with squamous epithelial cells (SEC) from the genital surfaces is assumed to be limited compared to clean-catch samples. However, no studies have quantified the change in predictive value in the presence of SECs for individual urinalysis markers.

Methods: In a retrospective, single center cohort study, we analyzed all urine cultures sent from the ED over a 26-month period with corresponding urinalysis results.

Comparison of bedside screening methods for frailty assessment in older adult trauma patients in the emergency department.

Background: Frailty is linked to poor outcomes in older patients. We prospectively compared the utility of the picture-based Clinical Frailty Scale (CFS9), clinical assessments, and ultrasound muscle measurements against the reference FRAIL scale in older adult trauma patients in the emergency department (ED).

Methods: We recruited a convenience sample of adults 65 yrs.

A Sepsis-related Diagnosis Impacts Interventions and Predicts Outcomes for Emergency Patients with Severe Sepsis.

Introduction: Many patients meeting criteria for severe sepsis are not given a sepsis-related diagnosis by emergency physicians (EP). This study 1) compares emergency department (ED) interventions and in-hospital outcomes among patients with severe sepsis, based on the presence or absence of sepsis-related diagnosis, and 2) assesses how adverse outcomes relate to three-hour sepsis bundle completion among patients fulfilling severe sepsis criteria but not given a sepsis-related diagnosis.

Methods: We performed a retrospective cohort study using patients meeting criteria for severe sepsis at two urban, academic tertiary care centers from March 2015 through May 2015.

Proteomic Clustering Analysis of SH2 Domain Datasets.

Proteomic clustering analysis provides a means of identifying relationships and visualizing those relationships in an extremely complex field of study with many interacting parts. With recent high-throughput studies of Src Homology 2 (SH2) domains, many and varied datasets are being amassed. A strategy for analyzing patterns between these large datasets is required to transform the information into knowledge.

Hidden Markov Models for Protein Domain Homology Identification and Analysis.

Protein domain identification and analysis are cornerstones of modern proteomics. The tools available to protein domain researchers avail a variety of approaches to understanding large protein domain families. Hidden Markov Models (HMM) form the basis for identifying and categorizing evolutionarily linked protein domains.

SRC Homology 2 Domain Binding Sites in Insulin, IGF-1 and FGF receptor mediated signaling networks reveal an extensive potential interactome.

Specific peptide ligand recognition by modular interaction domains is essential for the fidelity of information flow through the signal transduction networks that control cell behavior in response to extrinsic and intrinsic stimuli. Src homology 2 (SH2) domains recognize distinct phosphotyrosine peptide motifs, but the specific sites that are phosphorylated and the complement of available SH2 domains varies considerably in individual cell types. Such differences are the basis for a wide range of available protein interaction microstates from which signaling can evolve in highly divergent ways.

The SH2 domain-containing proteins in 21 species establish the provenance and scope of phosphotyrosine signaling in eukaryotes.

The Src homology 2 (SH2) domains are participants in metazoan signal transduction, acting as primary mediators for regulated protein-protein interactions with tyrosine-phosphorylated substrates. Here, we describe the origin and evolution of SH2 domain proteins by means of sequence analysis from 21 eukaryotic organisms from the basal unicellular eukaryotes, where SH2 domains first appeared, through the multicellular animals and increasingly complex metazoans. On the basis of our results, SH2 domains and phosphotyrosine signaling emerged in the early Unikonta, and the numbers of SH2 domains expanded in the choanoflagellate and metazoan lineages with the development of tyrosine kinases, leading to rapid elaboration of phosphotyrosine signaling in early multicellular animals.

SH2 domains recognize contextual peptide sequence information to determine selectivity.

Selective ligand recognition by modular protein interaction domains is a primary determinant of specificity in signaling pathways. Src homology 2 (SH2) domains fulfill this capacity immediately downstream of tyrosine kinases, acting to recruit their host polypeptides to ligand proteins harboring phosphorylated tyrosine residues. The degree to which SH2 domains are selective and the mechanisms underlying selectivity are fundamental to understanding phosphotyrosine signaling networks.

High-throughput phosphotyrosine profiling using SH2 domains.

Protein tyrosine phosphorylation controls many aspects of signaling in multicellular organisms. One of the major consequences of tyrosine phosphorylation is the creation of binding sites for proteins containing Src homology 2 (SH2) domains. To profile the global tyrosine phosphorylation state of the cell, we have developed proteomic binding assays encompassing nearly the full complement of human SH2 domains.

The human and mouse complement of SH2 domain proteins-establishing the boundaries of phosphotyrosine signaling.

SH2 domains are interaction modules uniquely dedicated to the recognition of phosphotyrosine sites and are embedded in proteins that couple protein-tyrosine kinases to intracellular signaling pathways. Here, we report a comprehensive bioinformatics, structural, and functional view of the human and mouse complement of SH2 domain proteins. This information delimits the set of SH2-containing effectors available for PTK signaling and will facilitate the systems-level analysis of pTyr-dependent protein-protein interactions and PTK-mediated signal transduction.