Risk factors for central venous catheter-related infections in surgical and intensive care units. The Central Venous Catheter-Related Infections Study Group.

To identify avoidable risk factors for central venous catheter (CVC) infections in patients undergoing short-term catheterization

Fuzzy branch‐and‐bound algorithm with owa operators in the case of consumer decision making

The ordered weighted averaging (OWA) operator is one of the most used techniques in the operator’s aggregation procedure. This paper proposes a new assignment algorithm by using the OWA operator and different extensions of it in the Branch‐and‐bound algorithm. The process is based on the use of the ordered weighted average distance operator (OWAD) and the induced OWAD operator (IOWAD). We present it as the Branch‐and‐bound algorithm with the OWAD operator (BBAOWAD) and the Branch‐and‐bound algorithm with the IOWAD operator (BBAIOWAD). The main advantage of this approach is that we can obtain more detailed information by obtaining a parameterized family of aggregation operators. The application of the new algorithm is developed in a consumer decision‐making model in the city of Barcelona regarding the selection of groceries by districts that best suit their needs. We rely on the opinion of local commerce experts in the city. The key advantage of this approach is that we can consider different sources of information independent of each other

Riluzole-Rasagiline Hybrids: Toward the Development of Multi-Target-Directed Ligands for Amyotrophic Lateral Sclerosis

Polypharmacology is a new trend in amyotrophic lateral sclerosis (ALS) therapy and an effective way of addressing a multifactorial etiology involving excitotoxicity, mitochondrial dysfunction, oxidative stress, and microglial activation. Inspired by a reported clinical trial, we converted a riluzole (1)-rasagiline (2) combination into single-molecule multi-target-directed ligands. By a ligand-based approach, the highly structurally integrated hybrids 3-8 were designed and synthesized. Through a target- and phenotypic-based screening pipeline, we identified hit compound 6. It showed monoamine oxidase A (MAO-A) inhibitory activity (IC50 = 6.9 mu M) rationalized by in silico studies as well as in vitro brain permeability. By using neuronal and non-neuronal cell models, including ALS-patient-derived cells, we disclosed for 6 a neuroprotective/neuroinflammatory profile similar to that of the parent compounds and their combination. Furthermore, the unexpected MAO inhibitory activity of 1 (IC50 = 8.7 mu M) might add a piece to the puzzle of its anti-ALS molecular profile

Seroprevalence of five neglected parasitic diseases among immigrants accessing five infectious and tropical diseases units in Italy: a cross-sectional study.

: This multicentre cross-sectional study aims to estimate the prevalence of five neglected tropical diseases (Chagas disease, filariasis, schistosomiasis, strongyloidiasis, toxocariasis) among immigrants accessing health care facilities in five Italian cities (Bologna, Brescia, Florence, Rome, Verona). : Individuals underwent a different set of serological tests, according to country of origin and presence of eosinophilia. Seropositive patients were treated and further followed up. : A total of 930 adult immigrants were enrolled: 477 men (51.3%), 445 women (47.9%), 8 transgender (0.8%); median age was 37.81 years (range 18-80). Most of them were coming from the African continent (405/930, 43.5%), the rest from East Europe, South America and Asia. A portion of 9.6% (89/930) were diagnosed with at least one of the infections under study. Seroprevalence of each specific infection varied from 3.9% (7/180) for Chagas diseases to 9.7% (11/113) for toxocariasis. Seropositive people were more likely to be 35 to 40 years-old male and to come from South East Asia, Sub-Saharan Africa or South America. : The results of our study confirm that neglected tropical diseases represent a substantial health problem among immigrants and highlight the need for addressing this emerging public health issue.<br/

Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease

Liver biology and function, drug-induced liver injury (DILI) and liver diseases are difficult to study using current in vitro models such as primary human hepatocyte (PHH) monolayer cultures, as their rapid de-differentiation restricts their usefulness substantially. Thus, we have developed and extensively characterized an easily scalable 3D PHH spheroid system in chemically-defined, serum-free conditions. Using whole proteome analyses, we found that PHH spheroids cultured this way were similar to the liver in vivo and even retained their inter-individual variability. Furthermore, PHH spheroids remained phenotypically stable and retained morphology, viability, and hepatocyte-specific functions for culture periods of at least 5 weeks. We show that under chronic exposure, the sensitivity of the hepatocytes drastically increased and toxicity of a set of hepatotoxins was detected at clinically relevant concentrations. An interesting example was the chronic toxicity of fialuridine for which hepatotoxicity was mimicked after repeated-dosing in the PHH spheroid model, not possible to detect using previous in vitro systems. Additionally, we provide proof-of-principle that PHH spheroids can reflect liver pathologies such as cholestasis, steatosis and viral hepatitis. Combined, our results demonstrate that the PHH spheroid system presented here constitutes a versatile and promising in vitro system to study liver function, liver diseases, drug targets and long-term DILI