LC/MS-Based Quantitative Proteomic Analysis of Paraffin-Embedded Archival Melanomas Reveals Potential Proteomic Biomarkers Associated with Metastasis

BACKGROUND: Melanoma metastasis status is highly associated with the overall survival of patients; yet, little is known about proteomic changes during melanoma tumor progression. To better understand the changes in protein expression involved in melanoma progression and metastasis, and to identify potential biomarkers, we conducted a global quantitative proteomic analysis on archival metastatic and primary melanomas. METHODOLOGY AND FINDINGS: A total of 16 metastatic and 8 primary cutaneous melanomas were assessed. Proteins were extracted from laser captured microdissected formalin fixed paraffin-embedded archival tissues by liquefying tissue cells. These preparations were analyzed by a LC/MS-based label-free protein quantification method. More than 1500 proteins were identified in the tissue lysates with a peptide ID confidence level of >75%. This approach identified 120 significant changes in protein levels. These proteins were identified from multiple peptides with high confidence identification and were expressed at significantly different levels in metastases as compared with primary melanomas (q-Value<0.05). CONCLUSIONS AND SIGNIFICANCE: The differentially expressed proteins were classified by biological process or mapped into biological system networks, and several proteins were implicated by these analyses as cancer- or metastasis-related. These proteins represent potential biomarkers for tumor progression. The study successfully identified proteins that are differentially expressed in formalin fixed paraffin-embedded specimens of metastatic and primary melanoma

Interventions to Improve Mental Health, Well-Being, Physical Health, and Lifestyle Behaviors in Physicians and Nurses: A Systematic Review

OBJECTIVE: This systematic review focused on randomized controlled trials (RCTs) with physicians and nurses that tested interventions designed to improve their mental health, well-being, physical health, and lifestyle behaviors. DATA SOURCE: A systematic search of electronic databases from 2008 to May 2018 included PubMed, CINAHL, PsycINFO, SPORTDiscus, and the Cochrane Library. STUDY INCLUSION AND EXCLUSION CRITERIA: Inclusion criteria included an RCT design, samples of physicians and/or nurses, and publication year 2008 or later with outcomes targeting mental health, well-being/resiliency, healthy lifestyle behaviors, and/or physical health. Exclusion criteria included studies with a focus on burnout without measures of mood, resiliency, mindfulness, or stress; primary focus on an area other than health promotion; and non-English papers. DATA EXTRACTION: Quantitative and qualitative data were extracted from each study by 2 independent researchers using a standardized template created in Covidence. DATA SYNTHESIS: Although meta-analytic pooling across all studies was desired, a wide array of outcome measures made quantitative pooling unsuitable. Therefore, effect sizes were calculated and a mini meta-analysis was completed. RESULTS: Twenty-nine studies (N = 2708 participants) met the inclusion criteria. Results indicated that mindfulness and cognitive-behavioral therapy-based interventions are effective in reducing stress, anxiety, and depression. Brief interventions that incorporate deep breathing and gratitude may be beneficial. Visual triggers, pedometers, and health coaching with texting increased physical activity. CONCLUSION: Healthcare systems must promote the health and well-being of physicians and nurses with evidence-based interventions to improve population health and enhance the quality and safety of the care that is delivered

Health-status outcomes with invasive or conservative care in coronary disease

BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline