Platelet proteome changes associated with diabetes and during platelet storage for transfusion.

Human platelets play a key role in hemostasis and thrombosis and have recently emerged as key regulators of inflammation. Platelets stored for transfusion produce pro-thrombotic and pro-inflammatory mediators implicated in adverse transfusion reactions. Correspondingly, these mediators are central players in pathological conditions including cardiovascular disease, the major cause of death in diabetics. In view of this, a mass spectrometry based proteomics study was performed on platelets collected from healthy and type-2 diabetics stored for transfusion. Strikingly, our innovative and sensitive proteomic approach identified 122 proteins that were either up- or down-regulated in type-2 diabetics relative to nondiabetic controls and 117 proteins whose abundances changed during a 5-day storage period. Notably, our studies are the first to characterize the proteome of platelets from diabetics before and after storage for transfusion. These identified differences allow us to formulate new hypotheses and experimentation to improve clinical outcomes by targeting "high risk platelets" that render platelet transfusion less effective or even unsafe.

The effects of shared peptides on protein quantitation in label-free proteomics by LC/MS/MS.

Assessment of differential protein abundance from the observed properties of detected peptides is an essential part of protein profiling based on shotgun proteomics. However, the abundance observed for shared peptides may be due to contributions from multiple proteins that are affected differently by a given treatment. Excluding shared peptides eliminates this ambiguity but may significantly decrease the number of proteins for which abundance estimates can be obtained. Peptide sharing within a family of biologically related proteins does not cause ambiguity if family members have a common response to treatment. On the basis of this concept, we have developed an approach for including shared peptides in the analysis of differential protein abundance in protein profiling. Data from a recent proteomics study of lung tissue from mice exposed to lipopolysaccharide, cigarette smoke, and a combination of these agents are used to illustrate our method. Starting from data where about half of the implicated database protein involved shared peptides, 82% of the affected proteins were grouped into families, based on FASTA annotation, with closure on peptide sharing. In many cases, a common abundance relative to control was sufficient to explain ion-current peak areas for peptides, both unique and shared, that identified biologically related proteins in a peptide-sharing closure group. On the basis of these results, we propose that peptide-sharing closure groups provide a way to include abundance data for shared peptides in quantitative protein profiling by high-throughput mass spectrometry.

Psychosocial correlates of patient-physician discordance in inflammatory bowel disease.

OBJECTIVE: The aim of this study was to identify the independent psychosocial correlates of patient-physician discordance in adult outpatients with inflammatory bowel disease. METHODS: This cross-sectional study was conducted in three university-affiliated tertiary care settings. Psychological distress, social support, perceived stress, and negative life events were assessed, as were demographic, lifestyle, and clinical characteristics. Patient-physician discordance was assessed with 10-item questionnaires. RESULTS: Ten gastroenterologists and 200 of their patients participated. Patients and their physicians disagreed most on discussion of personal issues. Patients with Crohn's disease had statistically significantly higher discordance on disease activity and physical limitation, as well as higher average overall discordance scores than patients with ulcerative colitis. Mean discordance levels were similar across different physicians. Higher psychological distress and more perceived stress were independently associated with higher discordance after controlling for Crohn's disease, active disease, being with the treating physician for less than 1 yr, and recommendation for further medical investigation. Psychological distress was the most important correlate of overall discordance. CONCLUSIONS: Increased physician awareness that psychologically distressed patients have difficulty processing of clinically relevant information may lead to improved doctor-patient communication during an office visit.

Predicting which patients can undergo upper endoscopy comfortably without conscious sedation.

BACKGROUND: Eliminating conscious sedation for diagnostic endoscopy may be advantageous for patient safety and cost containment. The aim of this study was to identify and validate independent predictors of a comfortable, technically adequate, unsedated diagnostic upper endoscopy in Canadian patients. METHODS: Patients were consecutively enrolled in a prospective fashion. Data collected on an initial cohort of 268 patients included demographics, a validated anxiety questionnaire, use of sedatives/analgesics, upper endoscopy experience, pharyngeal sensitivity, technical adequacy, and patient assessment of comfort after the procedure. The main outcome measure was "satisfactory upper endoscopy," a composite of optimal scores for patient comfort and technical adequacy. Univariate and multivariate analyses were performed to identify the optimal predictive model of a satisfactory unsedated diagnostic upper endoscopy. Once identified, 68 additional patients were enrolled in a similar fashion from an independent prospective sample for purposes of outcome validation. Multivariate analysis was then repeated with the total cohort (N = 336). These results were then compared for concordance with those obtained from the initial cohort. RESULTS: Among the initial 268 patients (54.3% women; mean age 51 +/- 17 years), 49% were anxious, 15% regularly used sedatives and analgesics, 28% experienced increased pharyngeal sensitivity, and 41% had previously undergone upper endoscopy. Endoscopy was completed in 94.7% of patients without sedation and was technically adequate in 97%, and 80.1% were willing to repeat the procedure under similar conditions. Satisfactory upper endoscopy was achieved in only 59% of the initial cohort. The only independent and significant predictors of a satisfactory upper endoscopy were advancing age (OR 1.2: 95% CI [1.1, 1.4]) and decreased pharyngeal sensitivity (OR 0.5: 95% CI [0.27, 0.93]). Concordance of results were noted after validation with the second cohort. Satisfactory endoscopy was achieved in only 59.5% of the total cohort (n = 336); only 61% reported a comfortable procedural experience. CONCLUSIONS: The proportion of patients who can comfortably undergo technically adequate unsedated upper endoscopy is modest. Unsedated upper endoscopy is most likely to be successful under these procedural conditions in patients of advancing age with decreased pharyngeal sensitivity. The generalizability of these findings to an American population requires further study and may assist in identifying a subgroup of patients in whom it is cost-effective to perform upper endoscopy comfortably without sedation.