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The poor prognosis of head and neck cancer (HNC) is associated with metastasis within the lymph nodes (LNs). Herein, the proteome of 140 multisite samples from a 59-HNC patient cohort, including primary and matched LN-negative or -positive tissues, saliva, and blood cells, reveals insights into the biology and potential metastasis biomarkers that may assist in clinical decision-making. Protein profiles are strictly associated with immune modulation across datasets, and this provides the basis for investigating immune markers associated with metastasis. The proteome of LN metastatic cells recapitulates the proteome of the primary tumor sites. Conversely, the LN microenvironment proteome highlights the candidate prognostic markers. By integrating prioritized peptide, protein, and transcript levels with machine learning models, we identify nodal metastasis signatures in blood and saliva. We present a proteomic characterization wiring multiple sites in HNC, thus providing a promising basis for understanding tumoral biology and identifying metastasis-associated signatures. The biological understanding of poor prognosis associated with lymph node metastasis in head and neck cancer (HNC) remains crucial. Here, a proteomic characterisation of 140 multisite samples from a 59-HNC patient cohort and machine learning reveals potential biomarkers and metastasis related signatures. [ABSTRACT FROM AUTHOR]

The poor prognosis of head and neck cancer (HNC) is associated with metastasis within the lymph nodes (LNs). Herein, the proteome of 140 multisite samples from a 59-HNC patient cohort, including primary and matched LN-negative or -positive tissues, saliva, and blood cells, reveals insights into the biology and potential metastasis biomarkers that may assist in clinical decision-making. Protein profiles are strictly associated with immune modulation across datasets, and this provides the basis for investigating immune markers associated with metastasis. The proteome of LN metastatic cells recapitulates the proteome of the primary tumor sites. Conversely, the LN microenvironment proteome highlights the candidate prognostic markers. By integrating prioritized peptide, protein, and transcript levels with machine learning models, we identify nodal metastasis signatures in blood and saliva. We present a proteomic characterization wiring multiple sites in HNC, thus providing a promising basis for understanding tumoral biology and identifying metastasis-associated signatures. The biological understanding of poor prognosis associated with lymph node metastasis in head and neck cancer (HNC) remains crucial. Here, a proteomic characterisation of 140 multisite samples from a 59-HNC patient cohort and machine learning reveals potential biomarkers and metastasis related signatures. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease and cardiovascular disease are highly prevalent conditions in the elderly. Evidence shows inconsistent findings regarding the association between Parkinson's disease and cardiovascular events. Objective: We sought to evaluate the proportion of cardiovascular adverse events among Parkinson's disease patients included in the placebo arm of randomized controlled trials. Methods: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to February 2017. Randomized, placebo-controlled trials in Parkinson's disease were included. The primary outcome was the proportion of major cardiovascular adverse events, defined as myocardial infarction, stroke, peripheral artery disease, and sudden death. A random-effects meta-analysis was performed to derive pooled estimates of the proportion of adverse events and corresponding 95% confidence intervals (CIs). Results: 236 randomized controlled trials were included, 80% (n = 189; 14704 patients) of which reported data on cardiovascular adverse events. The pooled proportion of major cardiovascular events ranged from 0.00% to 0.06% and the proportion of all cardiovascular adverse events was 3.33% (95% CI: 2.14, 4.70%), and ranged from 1.71% in de novo Parkinson's disease patients to 4.56% in patients receiving levodopa as their only antiparkinsonian medication. The most common adverse events were hypertension and orthostatic hypotension. Conclusions: These results suggest that the proportion of major cardiovascular adverse events is low and that blood pressure abnormalities are the most frequent cardiovascular adverse event. [ABSTRACT FROM AUTHOR]

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What is known Spironolactone is used in paediatric patients with heart disease, yet few data are available regarding the impact on potassium supplementation. Objective We sought to determine the effect of spironolactone on potassium supplementation in paediatric cardiac intensive care patients. Methods A retrospective, propensity matched cohort study was designed. Patients were included in the study if they received furosemide therapy in the cardiac intensive care unit at our institution. Patients who received spironolactone were matched to patients who did not receive spironolactone. Data collection included patient demographics, diuretic data, potassium monitoring, and total milliequivalents of potassium administered during the cardiac intensive care unit stay. Results and discussion A total of 448 patients met study criteria median age 0.43 ( IQR 0.06-3.52) years, 58.9% male. Intensive care unit length of stay was 7 ( IQR 3-17) days, cardiovascular surgery occurred in 90.4%. Patients had a mean 4.6±2.6 potassium concentrations assessed per day (29.5%±19.4%<3.5 mmol/L, and 2.9%±6.5%>5.5 mmol/L). Patients received a median of 5.1 mEq/kg (0-323.4 mEq/kg) of potassium. Spironolactone (n=224) was administered for 2 days ( IQR 1-4) at mean dose of 0.64±0.54 mg kg−1 d−1. Median total mEq/kg of potassium administered did not differ between groups (4.6 mEq/kg ( IQR 0.66-16.8) vs 6.5 mEq/kg ( IQR 1.3-18.3 mEq/kg), P=.13). Potassium laboratory values did not differ in hypokalemia (27.8%±19.1% vs 31.2%±19.5%, P=.06) or hyperkalemia (2.8%±5.4% vs 3.2%±7.5%, P=.49) between groups. What is new Spironolactone supplementation did not reduce the need for potassium supplementation in paediatric cardiac intensive care patients. Conclusion The routine use of spironolactone in the paediatric cardiac intensive care population may not be more efficacious than potassium supplementation for maintenance of serum potassium concentrations. [ABSTRACT FROM AUTHOR]

Purpose: Since pesticides are disputed risk factors for uveal melanoma, we studied the association between occupational pesticide exposure and uveal melanoma risk in a case-control study from nine European countries. Methods: Incident cases of uveal melanoma and population as well as hospital controls were included and frequency-matched by country, 5-year age groups and sex. Self-reported exposure was quantified with respect to duration of exposure and pesticide application method. We calculated the exposure intensity level based on application method and use of personal protective equipment. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression analyses and adjusted for several potential confounders. Results: 293 case and 3,198 control subjects were interviewed. We did not identify positive associations with activities in farming or forestry, pesticide application or pesticide mixing. No consistent positive associations were seen with exposure intensity level scores either. The only statistically significantly raised association in this study was for exposure to chemical fertilizers in forestry (OR = 8.93; 95% CI 1.73-42.13), but this observation was based on only six exposed subjects. Results did not change when we restricted analyses to morphologically verified cases and excluded proxy interviews as well as cancer controls. We did not observe effect modification by sex or eye color. Conclusions: Risk estimates for pesticide exposures and occupational activities in agriculture and forestry were not increased and did not indicate a hormonal mechanism due to these exposures. [ABSTRACT FROM AUTHOR]

Examines the behavior of the minimum mean-squared error (MMSE) receiver in frequency-nonselective-fading channels. Basic system models and equations; The MMSE detector; Performance of the MMSE detector in a single-user environment; The modified MMSE receiver; Conclusions.