N-(aroyl)-N-(arylmethyloxy)-α-alanines: selective inhibitors of aldose reductase

Aldose reductase (ALR2), a NADPH-dependent reductase, is the first and rate-limiting enzyme of the polyol pathway of glucose metabolism and is implicated in the pathogenesis of secondary diabetic complications. In the last decades, this enzyme has been targeted for inhibition but despite the numerous efforts made to identify potent and safe ALR2 inhibitors, many clinical candidates have been a failure. For this reason the research of new ALR2 inhibitors highly effective, selective and with suitable pharmacokinetic properties is still of great interest. In this paper some new N-(aroyl)-N-(arylmethyloxy)alanines have been synthesized and tested for their ability to inhibit ALR2. Some of the synthesized compounds exhibit IC50 in the low micromolar range and all have proved to be highly selective towards ALR2. The N-(aroyl)-N-(arylmethyloxy)-α-alanines are a promising starting point for the development of new ALR2 selective drugs with the aim of delaying the onset of diabetic complications

The management of healthcare-related infections through lean methodology: systematic review and meta-analysis of observational studies.

Introduction: Lean is largely applied to the health sector and on the healthcare-associated infections (HAI). However, a few results on the improvement of the outcome have been reported in literature. The purpose of this study is to analyze if the lean application can reduce the HAI rate. Methods: A comprehensive search was performed on PubMed/Medline, Scopus, CINAHL, Cochrane, Embase, and Google Scholar databases using various combinations of the following keywords: "lean" and "infection". Inclusion criteria were: 1) research articles with quantitative data and relevant information on lean methodology and its impact on healthcare infections; 2) prospective studies. The risk of bias and the study quality was independently assessed by two researchers using the “The National Institutes of Health (NIH) quality assessment tool for before-after (Pre-Post) study with no control group”. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines has been used. 22 studies were included in the present meta-analysis. Results: Lean application demonstrated a significant protective role on healthcare-associated infections rate (RR 0.50 [0.38-0.66]) with significant impact on central line-associated bloodstream infections (CLABSIs) (RR 0.47 [0.28-0.82]). Conclusions: Lean has a positive impact on the decreasing of HAIs and on the improvement of compliance and satisfaction of the staff

A Clostridium difficile outbreak in an Italian hospital: the efficacy of the multi-disciplinary and multifaceted approach

Introduction: We described an outbreak of C. difficile that occurred in the Internal Medicine department of an Italian hospital and assessed the efficacy of the measures adopted to manage the outbreak.Methods: The outbreak involved 15 patients and was identified by means of continuous integrated microbiological surveillance, starting with laboratory data (alert organism surveillance).Diarrheal fecal samples from patients with suspected infection by C. difficile underwent rapid membrane immuno-enzymatic testing, which detects both the presence of the glutamate dehydrogenase antigen and the presence of the A and B toxins.Extensive microbiological sampling was carried out both before and after sanitation of the environment, in order to assess the efficacy of the sanitation procedure.Results: The outbreak lasted one and a half month, during which time the Committee for the Prevention of Hospital Infections ordered the implementation of multiple interventions, which enabled the outbreak to be controlled and the occurrence of new cases to be progressively prevented.The strategies adopted mainly involved patient isolation, reinforcement of proper hand hygiene techniques, antimicrobial stewardship and environmental decontamination by means of chlorine-based products. Moreover, the multifaceted management of the outbreak involved numerous sessions of instruction/training for nursing staff and socio-sanitary operatives during the outbreak.Sampling of environmental surfaces enabled two sites contaminated by C. difficile to be identified.Conclusions: Joint planning of multiple infection control practices, together with effective communication and collaboration between the Hospital Infections Committee and the ward involved proved to be successful in controlling the outbreak

Epidemiology, management, and outcome of carbapenem-resistant Klebsiella pneumoniae bloodstream infections in hospitals within the same endemic metropolitan area

In the last decade, carbapenem-resistant Klebsiella pneumoniae (CR-Kp) has become endemic in several countries, including Italy. In the present study, we assessed the differences in epidemiology, management, and mortality of CR-Kp bloodstream infection (BSI) in the three main adult acute-care hospitals of the metropolitan area of Genoa, Italy.From January 2013 to December 2014, all patients with CR-Kp BSI were identified through the computerized microbiology laboratory databases of the three hospitals. The primary endpoints of the study were incidence and characteristics of CR-Kp BSI in hospitals within the same endemic metropolitan area. Secondary endpoints were characteristics of CR-Kp BSI in hospitals with and without internal infectious diseases consultants (IDCs) and 15-day mortality.During the study period, the incidence of healthcare-associated CR-Kp BSI in the entire study population was 1.35 episodes per 10,000 patient-days, with substantial differences between the three hospitals. Patients admitted to the two hospital with internal IDCs were more likely to receive post-susceptibility test combined therapy including carbapenems (77% vs. 26%, p <. 0.001), adequate post-susceptibility test therapies (86% vs. 52%, p <. 0.001), and post-susceptibility therapies prescribed by an infectious diseases specialist (84% vs. 14%, p <. 0.001). Overall, the crude 15-days mortality was 26%. In the final multivariable model, only septic shock at BSI presentation was unfavorably and independently associated with 15-days mortality (odds ratio [OR] 6.7, 95% confidence intervals [CI] 2.6-17.6, p <. 0.001), while a protective effect was observed for post-susceptibility test combined therapies including a carbapenem (OR 0.11, 95% CI 0.03-0.43, p = 0.002).Mortality of CR-Kp remains high. Differences in the incidence of CR-Kp BSI were detected between acute-care centers within the same endemic metropolitan area. Efforts should be made to improve the collaboration and coordination between centers, to prevent further diffusion of CR-Kp

Inhibition of ERK1/2 signaling prevents bone marrow fibrosis by reducing osteopontin plasma levels in a myelofibrosis mouse model

Clonal myeloproliferation and development of bone marrow (BM) fibrosis are the major pathogenetic events in myelofibrosis (MF). The identification of novel antifibrotic strategies is of utmost importance since the effectiveness of current therapies in reverting BM fibrosis is debated. We previously demonstrated that osteopontin (OPN) has a profibrotic role in MF by promoting mesenchymal stromal cells proliferation and collagen production. Moreover, increased plasma OPN correlated with higher BM fibrosis grade and inferior overall survival in MF patients. To understand whether OPN is a druggable target in MF, we assessed putative inhibitors of OPN expression in vitro and identified ERK1/2 as a major regulator of OPN production. Increased OPN plasma levels were associated with BM fibrosis development in the Romiplostim-induced MF mouse model. Moreover, ERK1/2 inhibition led to a remarkable reduction of OPN production and BM fibrosis in Romiplostim-treated mice. Strikingly, the antifibrotic effect of ERK1/2 inhibition can be mainly ascribed to the reduced OPN production since it could be recapitulated through the administration of anti-OPN neutralizing antibody. Our results demonstrate that OPN is a novel druggable target in MF and pave the way to antifibrotic therapies based on the inhibition of ERK1/2-driven OPN production or the neutralization of OPN activity

Characterisation of brewpub beer carbohydrates using high performance anion exchange chromatography coupled with pulsed amperometric detection

High performance anion exchange chromatography (HPAEC) coupled with pulsed amperometric detection (PAD) was optimised in order to quantify mannose, maltose, maltotriose, maltotetraose, maltopentaose, maltohexaose and maltoheptaose content of beer. The method allows the determination of above mentioned oligosaccharides, in a single chromatographic run, without any pre-treatment. Limit of detection and limit of quantification were suitable for beer. Accuracy and repeatability were good for the entire amount considered. Once optimised HPAEC PAD for the specific matrix, the second goal of this research was to verify the possibility to discriminate beers, depending on their style. The carbohydrates content of brewpub commercial beers was very variable, ranging from 19.3 to 1469 mg/L (mannose), 34.5 to 2882 mg/L (maltose), 141.9 to 20731 mg/L (maltotriose), 168.5 to 7650 mg/L (maltotetraose), 20.1 to 2537 mg/L (maltopentaose), 22.9 to 3295 mg/L (maltohexaose), 8.5 to 2492 mg/L (maltoeptaose), even in the same style of beer. However, the carbohydrates content was useful, jointed with other compounds amount, to discriminate different styles of beer. As a matter of fact, principal component analysis put in evidence beer differences considering some fermentation conditions and colour

Comparison of traditional and reductive winemaking: influence on some fixed components and sensorial characteristics

An explorative study to verify the applicabilityof reductive winemaking (RW) on two cultivars was carriedout. To this purpose, traditional winemaking (TW) andRW were carried out on a semi-aromatic white grape(Sauvignon blanc) and a white neutral one (Trebbianoromagnolo). All phenolic parameters were higher in RWwines, while other substances such as alcohol, reducingsugars, acids, and volatile acidity acids were less affectedby the different winemaking technique. A deeper yellowcolor (OD 420) was a direct consequence of the higherphenolic content of RW wines, while OD 320 was strictlyrelated to caftaric acid integrity. Analyses showed a modificationof the RW wines, also in the case of a neutralcultivar. Principal component analysis (PCA) was appliedto the data set, and the first two PCs explained almost 85%of the total variability and divided TW and RW wines intwo groups to demonstrate that the effect of winemakingoverwhelmed maturation differences. Panelists preferredRW wines, which were characterized by a richer and moredelicate aroma. The study demonstrated that a carefulexclusion of air combined with an effective oxidationprevention yields to more characterized and pleasant wines

Impact of wooden barrel storage on the volatile composition and sensorial profile of red wine

This study determined the influence of the kind of wood (Allier vs Limousin and Allier vs chestnut), the age (new vs 1 year old Allier oak barriques) and the volume (1000L vs 225L ) of Allier oak containers on sensorial profile and volatile composition of a red Sangiovese wine during 360 days of ageing. The greatest sensory differences were found between Allier oak wood and chestnut wood barriques. In chestnut barriques, wines were more fruited and tannic than in Allier where wines were less astringent, more vanilla flavoured and well-balanced. Some differences in chemical composition and sensorial profile were observed in wines aged in used containers with different capacities. The use of containers showed that migration phenomena from wood to wine were more intense in new barriques than in used ones. Therefore, wines aged in new barriques were richer in volatile wood compounds than wines aged in old barriques.[...

Mechanical harvesting optimization and postharvest treatments to improve wine quality

Aims: The aim of this work was to verify the influence of mechanical harvesting and postharvest treatments on wine composition. Methods and results: Trials were carried out in triplicate on cv. Montuni grapes. The estimated best setting frequency for the mechanical harvester was 410 shakes/min. Comparing hand-picked and mechanically harvested grapes, the reduced extract and pH results were lower for the hand-picked grapes, showing a more evident berry breakage caused by the mechanical harvester. The wines obtained from mechanically harvested grapes had a lower phenolic compound content than wines produced with hand-picked grapes, indicating that oxidation phenomena occurred; the trend for postharvest treated grapes was different. The significantly lower amount of higher alcohols in the hand-picked grapes trial than in the mechanically harvested ones could be explained by a lower amount of their precursors and oxygen in musts. The sensory differences among the trials were significant for some parameters, but an overall view of the data suggested that the differences were not remarkable and all the wines were good. Conclusion: Postharvest treatments reduce the loss of natural antioxidant compounds found in wines produced from mechanically harvested grapes. Mechanical harvesting does not have a negative influence on wine composition if matched with the proper vineyard characteristics, machine settings and postharvest treatments. The typicality of Montuni wine is maintained in the cases of grapes harvested mechanically with, but also without, any postharvest treatment. The use of these treatments is otherwise useful to obtain wines with a better stability. Significance and impact of the study: With respect to mechanical harvesting, this study highlights the importance of maintaining and/or improving the quality of mechanically harvested grapes containing the harvesting costs