Urinary proteomics pilot study for biomarker discovery and diagnosis in heart failure with reduced ejection fraction

Background Biomarker discovery and new insights into the pathophysiology of heart failure with reduced ejection fraction (HFrEF) may emerge from recent advances in high-throughput urinary proteomics. This could lead to improved diagnosis, risk stratification and management of HFrEF. Methods and Results Urine samples were analyzed by on-line capillary electrophoresis coupled to electrospray ionization micro time-of-flight mass spectrometry (CE-MS) to generate individual urinary proteome profiles. In an initial biomarker discovery cohort, analysis of urinary proteome profiles from 33 HFrEF patients and 29 age- and sex-matched individuals without HFrEF resulted in identification of 103 peptides that were significantly differentially excreted in HFrEF. These 103 peptides were used to establish the support vector machine-based HFrEF classifier HFrEF103. In a subsequent validation cohort, HFrEF103 very accurately (area under the curve, AUC = 0.972) discriminated between HFrEF patients (N = 94, sensitivity = 93.6%) and control individuals with and without impaired renal function and hypertension (N = 552, specificity = 92.9%). Interestingly, HFrEF103 showed low sensitivity (12.6%) in individuals with diastolic left ventricular dysfunction (N = 176). The HFrEF-related peptide biomarkers mainly included fragments of fibrillar type I and III collagen but also, e.g., of fibrinogen beta and alpha-1-antitrypsin. Conclusion CE-MS based urine proteome analysis served as a sensitive tool to determine a vast array of HFrEF-related urinary peptide biomarkers which might help improving our understanding and diagnosis of heart failure

Reduced exploration capacity despite brain volume increase in warm-acclimated common minnow

While evidence suggests that warming may impact cognition of ectotherms, the underlying mechanisms remain poorly understood. A possible but rarely considered mechanism is that the metabolic response of ectotherms to warming is associated with changes in brain morphology and function. Here, we compared aerobic metabolism, brain volume, boldness and accuracy of maze solving of common minnows (Phoxinus phoxinus) acclimated for 8 months to either their current optimal natural (14°C) or warm (20°C) water temperature. Metabolic rates indicated increased energy expenditure in warm-acclimated fish, but also at least partial thermal compensation as warm-acclimated fish maintained high aerobic scope. Warm-acclimated fish had larger brains than cool-acclimated fish. The volume of the dorsal medulla relative to the overall brain size was larger in warm- than in cool-acclimated fish, but the proportion of other brain regions did not differ between the temperature treatments. Warm-acclimated fish did not differ in boldness but made more errors than cool-acclimated fish in exploring the maze across four trials. Inter-individual differences in the number of exploration errors were repeatable across the four trials of the maze test. Our findings suggest that in warm environments, maintaining a high aerobic scope, which is important for the performance of physically demanding tasks, can come at the cost of changes in brain morphology and impairment of the capacity to explore novel environments. This trade-off could have strong fitness implications for wild ectotherms

Interventions to Reduce Medication Dispensing, Administration, and Monitoring Errors in Pediatric Professional Healthcare Settings: A Systematic Review

Introduction: Pediatric patients cared for in professional healthcare settings are at high risk of medication errors. Interventions to improve patient safety often focus on prescribing; however, the subsequent stages in the medication use process (dispensing, drug administration, and monitoring) are also error-prone. This systematic review aims to identify and analyze interventions to reduce dispensing, drug administration, and monitoring errors in professional pediatric healthcare settings. Methods: Four databases were searched for experimental studies with separate control and intervention groups, published in English between 2011 and 2019. Interventions were classified for the first time in pediatric medication safety according to the "hierarchy of controls" model, which predicts that interventions at higher levels are more likely to bring about change. Higher-level interventions aim to reduce risks through elimination, substitution, or engineering controls. Examples of these include the introduction of smart pumps instead of standard pumps (a substitution control) and the introduction of mandatory barcode scanning for drug administration (an engineering control). Administrative controls such as guidelines, warning signs, and educational approaches are lower on the hierarchy and therefore predicted by this model to be less likely to be successful. Results: Twenty studies met the inclusion criteria, including 1 study of dispensing errors, 7 studies of drug administration errors, and 12 studies targeting multiple steps of the medication use process. A total of 44 interventions were identified. Eleven of these were considered higher-level controls (four substitution and seven engineering controls). The majority of interventions (n = 33) were considered "administrative controls" indicating a potential reliance on these measures. Studies that implemented higher-level controls were observed to be more likely to reduce errors, confirming that the hierarchy of controls model may be useful in this setting. Heterogeneous study methods, definitions, and outcome measures meant that a meta-analysis was not appropriate. Conclusions: When designing interventions to reduce pediatric dispensing, drug administration, and monitoring errors, the hierarchy of controls model should be considered, with a focus placed on the introduction of higher-level controls, which may be more likely to reduce errors than the administrative controls often seen in practice. Trial Registration Prospero Identifier: CRD42016047127

Changing species distribution and antimicrobial susceptibility pattern of Shigella over a 29-year period (1980-2008)

We studied changes in species distribution and antimicrobial resistance patterns of Shigella during 1980-2008, using the Diarrhoeal Diseases Surveillance system of Dhaka Hospital of ICDDR,B. In hospitalized patients Shigella prevalence decreased steadily from 8-12% in the 1980s to 3% in 2008. Endemic S. flexneri was the most commonly isolated species (54%). Epidemic S. dysenteriae type 1 had two peaks in 1984 and 1993, but was not found after 2000, except for one case in 2004. The therapeutic options are now limited: in 2008 a total of 33% of S. flexneri were resistant to ciprofloxacin and 57% to mecillinam. In the <5 years age group, severely underweight, wasted and stunted children were more at risk of shigellosis compared to well-nourished children (P<0·001). Although hospitalization for Shigella diarrhoea is decreasing, the high levels of antimicrobial resistance and increased susceptibility of malnourished children continue to pose an ongoing ris