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The journal transferred to Wolters Kluwer effective 1 January 2018 and all Articles in Press will be published by the new publisher as a result. This Article in Press has therefore been withdrawn from this platform. Should you have any queries please contact the Editor-in-Chief, Prof. Abdulmonem Al-Hayani at hayani30@hotmail.com. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

The article focuses on the importance of job satisfaction for nurse practitioners and provides advice on creating a happy and profitable practice. Topics discussed include opportunities for professional growth, clear job responsibilities and expectations, collaboration with others, incentivized goals, involvement in clinic systems, effective hiring and management strategies, pacing when adding new services, adopting a leadership approach, and measuring performance indicators.

Human germinal center (GC)–associated lymphoma (HGAL) is an adaptor protein expressed in GC B cells. HGAL regulates cell motility and B-cell receptor (BCR) signaling, processes that are central for the successful completion of the GC reaction. Herein, we demonstrate phosphorylation of HGAL by Syk and Lyn kinases at tyrosines Y80, Y86, Y106Y107, Y128, and Y148. The HGAL YEN motif (amino acids 107-109) is similar to the phosphopeptide motif pYXN used as a binding site to the growth factor receptor–bound protein 2 (Grb2). We demonstrate by biochemical and molecular methodologies that HGAL directly interacts with Grb2. Concordantly, microscopy studies demonstrate HGAL-Grb2 colocalization in the membrane central supramolecular activation clusters (cSMAC) following BCR activation. Mutation of the HGAL putative binding site to Grb2 abrogates the interaction between these proteins. Further, this HGAL mutant localizes exclusively in the peripheral SMAC and decreases the rate and intensity of BCR accumulation in the cSMAC. Furthermore, we demonstrate that Grb2, HGAL, and Syk interact in the same complex, but Grb2 does not modulate the effects of HGAL on Syk kinase activity. Overall, the interplay between the HGAL and Grb2 regulates the magnitude of BCR signaling and synapse formation.

According to the current literature, biliary lithiasis is a worldwide-diffused condition that affects almost 20% of the general population. The rate of common bile duct stones (CBDS) in patients with symptomatic cholelithiasis is estimated to be 10% to 33%, depending on patient's age. Compared to stones in the gallbladder, the natural history of secondary CBDS is still not completely understood. It is not clear whether an asymptomatic choledocholithiasis requires treatment or not. For many years, open cholecystectomy with choledochotomy and/or surgical sphincterotomy and cleaning of the bile duct were the gold standard to treat both pathologies. Development of both endoscopic retrograde cholangiopancreatography (ERCP) and laparoscopic surgery, together with improvements in diagnostic procedures, influenced new approaches to the management of CBDS in association with gallstones.

ABSTRACTAsplenic or hyposplenic (AH) individuals are particularly vulnerable to invasive infections caused by encapsulated bacteria. Such infections have often a sudden onset and a fulminant course. Infectious diseases (IDs) incidence in AH subjects can be reduced by preventive measures such as vaccination. The aim of our work is to provide updated recommendations on prevention of infectious diseases in AH adult patients, and to supply a useful and practical tool to healthcare workers for the management of these subjects, in hospital setting and in outpatients consultation. A systematic literature review on evidence based measures for the prevention of IDs in adult AH patients was performed in 2015. Updated recommendations on available vaccines were consequently provided. Vaccinations against S. pneumoniae, N. meningitidis, H. influenzaetype b and influenza virus are strongly recommended and should be administered at least 2 weeks before surgery in elective cases or at least 2 weeks after the surgical intervention in emergency cases. In subjects without evidence of immunity, 2 doses of live attenuated vaccines against measles-mumps-rubella and varicella should be administered 4–8 weeks apart from each other; a booster dose of tetanus, diphtheria and pertussis vaccine should be administered also to subjects fully vaccinated, and a 3-dose primary vaccination series is recommended in AH subjects with unknown or incomplete vaccination series (as in healthy people). Evidence based prevention data support the above recommendations to reduce the risk of infection in AH individuals.

Esophageal carcinoma is the eighth most frequent cancer worldwide and the sixth cancer-related cause of death. Here we propose a new meta-analysis to identify the most appropriate approach for resectable adenocarcinoma of the distal esophagus and cardia (Siewert 1-2). A systematic literature search was performed independently by 2 of the manuscript's authors using PubMed, EMBASE, Scopus and the Cochrane Library Central. The following criteria were set for inclusion in this meta-analysis: 1) studies comparing transthoracic esophagectomy and transhiatal esophagectomy for adenocarcinoma of the esophagus; 2) studies reporting at least 1 perioperative outcome; and 3) if more than 1 study was reported by the same institute, only the most recent or the highest quality study was included. A total of 6 articles dated between 1996 and 2012 fulfilled the selection criteria and were therefore included in this meta-analysis; this pool of articles consisted of 2 prospective and 4 retrospective studies. A statistically significant difference favoring the transthoracic procedure was noted regarding the number of retrieved lymph nodes, 5-year disease-free survival rate and 5-year overall survival rate (p = 0.001, p = 0.05 and p = 0.03, respectively). In conclusion, transthoracic esophagectomy for adenocarcinoma of the distal esophagus and esophagogastric junction (Siewert 1-2) appears to be superior to the transhiatal approach in terms of oncological outcomes.

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by welldefined neuropathological brain changes including amyloid plaques, neurofibrillary tangles and the presence of chronic neuroinflammation. Objective: The brain penetrant BET bromodomain inhibitor JQ1 has been shown to regulate inflammation responses in vitro and in vivo, but its therapeutic potential in AD is currently unknown. Method: Three-month-old 3xTg mice were injected once a day with JQ1 (50 mg/kg) or vehicle for 15 weeks. At the end of the treatment learning and memory was assessed using the modified Barnes maze and the Y maze behavioral tests. Tissue from the brain and other organs was collected for molecular evaluation of neuroinflammation tau pathology and amyloid β. Results: JQ1 treatment reduced splenomegaly and neuroinflammation in the brain of treated mice where we observed a reduction in the expression of the pro-inflammatory modulators Il-1b, Il-6, Tnfa, Ccl2, Nos2 and Ptgs2. Additionally, JQ1-treated mice showed a reduction of tau phosphorylation at Ser396 in the hippocampus and frontal cortex while total levels of tau remained unaffected. On the other hand, JQ1 did not ameliorate learning and memory deficits in 7-month-old 3xTg mice. Conclusion: Taken together, our data suggest that BET bromodomain inhibitors hold the promise to be used for the treatment of neurological disorders characterized by neuroinflammation.

Long non-coding RNAs (lncRNAs), including natural antisense transcripts (NATs), are expressed more extensively than previously anticipated and have widespread roles in regulating gene expression. Nevertheless, the molecular mechanisms of action of the majority of NATs remain largely unknown. Here, we identify a NAT of low-density lipoprotein receptor-related protein 1 (Lrp1), referred to as Lrp1-AS, that negatively regulates Lrp1expression. We show that Lrp1-AS directly binds to high-mobility group box 2 (Hmgb2) and inhibits the activity of Hmgb2 to enhance Srebp1a-dependent transcription of Lrp1. Short oligonucleotides targeting Lrp1-AS inhibit the interaction of antisense transcript and Hmgb2 protein and increase Lrp1expression by enhancing Hmgb2 activity. Quantitative RT-PCR analysis of brain tissue samples from Alzheimer’s disease patients and aged-matched controls revealed upregulation of LRP1-AS and downregulation of LRP1. Our data suggest a regulatory mechanism whereby a NAT interacts with a ubiquitous chromatin-associated protein to modulate its activity in a locus-specific fashion.

Esophagojejunal anastomosis leakage is one of the major complications after total gastrectomy for gastric cancer and is an independent predictor of survival. Our aim is to systematically review the literature and discuss the reported therapeutic approaches to identify the best therapeutic approach. Pubmed, EMbase, Cochrane Library, CILEA Archive, BMJ Clinical Evidence, and Up ToDate databases were screened limiting the research to articles written in English from January 1992 through December 2013. This way a total of 474 manuscripts were retrieved for furthermore evaluation. Eleven manuscripts were considered eligible and the study is focused on those works. We analyzed a total of 3,893 patients and 114 cases of esophagojejunal anastomosis leakage. Different treatments were grouped into three main categories: conservative approach (66 cases), endoscopic approach (21 cases), and surgical approach (27 cases). The overall mortality rate is 26.32 per cent and surgical approach showed the higher rate. According to the reported data, a complete resolution of the leakage can be achieved in an interval ranging from 7 to 28 days in the group treated conservatively. Conservative approach should always be considered as the treatment of choice. Reoperation may be necessary in case of wide dehiscence or when other treatments fail; therefore, the high mortality rate related to this procedure is due to the comorbidities of patients undergoing relaparotomy. Finally, endoscopic approach with endoclips seems promising but needs furthermore studies.

De novomalignancies represent an important cause of death for liver transplant recipients. Our aim was to analyze predictors of extra-hepatic non-skin cancer (ESNSC) and the impact of ESNSC on the long-term outcome.

We assessed hand hygiene adherence in 2 infectious disease units. In one unit, adherence declined slightly from year 1 (84.2%) to year 4 (71.0%) after a multimodal intervention but remained much higher than before intervention. Adherence dropped in the second unit after a loss of leadership (from 50.7% to 5.7%). Strong leadership presence may improve hand hygiene adherence.

Apolipoprotein A1 (APOA1) is the major protein component of high-density lipoprotein (HDL) in plasma. We have identified an endogenously expressed long noncoding natural antisense transcript, APOA1-AS, which acts as a negative transcriptional regulator of APOA1 both in vitro and in vivo. Inhibition of APOA1-ASin cultured cells resulted in the increased expression of APOA1 and two neighboring genes in the APOcluster. Chromatin immunoprecipitation (ChIP) analyses of a ∼50 kb chromatin region flanking the APOA1gene demonstrated that APOA1-AScan modulate distinct histone methylation patterns that mark active and/or inactive gene expression through the recruitment of histone-modifying enzymes. Targeting APOA1-ASwith short antisense oligonucleotides also enhanced APOA1expression in both human and monkey liver cells and induced an increase in hepatic RNA and protein expression in African green monkeys. Furthermore, the results presented here highlight the significant local modulatory effects of long noncoding antisense RNAs and demonstrate the therapeutic potential of manipulating the expression of these transcripts both in vitro and in vivo.

Nodal ratio (NR) has been demonstrated to be an important prognostic factor in patients with gastric cancer. The aim of this study is to evaluate the prognostic role of nodal ratio comparing it with the new TNM (2010) classification. One hundred forty-two patients were submitted to potentially curative gastrectomy for cancer. Patients with low performance status underwent D1.5 lymphadenectomy, whereas the other patients underwent D2–D2.5 lymphadenectomy. Nodal staging was classified according to 2010 International Union Against Cancer/American Joint Committee on Cancer classification. Kaplan-Meier method was used to evaluate survival, stratified for nodal classes and nodal status. Total gastrectomy was performed in 39 per cent of cases and distal gastrectomy in 61 per cent. Mean number of resected nodes was 25.5. Whereas N status was strictly related to the number of resected nodes, the NR was independent from the extension of the lymphadenectomy. Overall five-year survival was 81 per cent for N0 patients, 72 per cent for N1, and 26 and 23 per cent for N2 and N3, respectively. Patients with NR0 had 81 per cent five-year survival, whereas NR1 67 per cent, NR2 51 per cent, and NR3 22 per cent. NR seems to be a simple method to predict the prognosis of patients with gastric cancer; unlike N status, it is independent from the number of resected nodes, and therefore it is particularly useful in case of inadequate lymphadenectomy.

One of the main challenges in the perspective of a hydrogen economy is the development of a storage system both safe and with high weight capacity. Among the most promising systems are the storage in metals and chemical hydrides and the high pressure storage in tanks made of composite materials. Both these technologies allow volumetric densities equal or higher than that of liquid hydrogen. The present work deals with the results obtained in a Italian national project, whose objectives have been the development of innovative technologies in specific applications: large scale energy storage, stationary applications in distributed generation, and automotive (with a particular attention to the fluvial and the sea transportation in protected areas). The theoretical, modellistic and experimental activities have been oriented to the development of innovative high capacity metal hydrides, the study of a regeneration method for chemical hydrides, the integration of intermediate pressure electrolyzers with advanced compressors and, finally, the development of thermomechanical models for executive design of storage systems. A number of prototypes has been realised and installed in a test facility in the Fusina (Venezia) power plant. The activity has been completed with an executive feasibility evaluation, in the perspective of industrial applications.

The discovery of RNA interference (RNAi) has opened new avenues in biology and medicine. In addition to post-transcriptional gene silencing, new findings are expanding the range of action of small duplex RNAs and broadening the spectrum of the potential applications of RNAi-based therapeutics. In recent years a complex and heterogeneous network of non-protein coding RNAs (ncRNAs) with potential regulatory functions has come into the spotlight providing an unexpected perspective on the mechanisms of transcriptional and epigenetic control of gene expression in human cells. The spread and complexity of these RNA-based transcriptional regulatory networks are still to be explored. However, they are likely to be important mechanisms controlling gene expression in human cells. As we will learn more about these processes, endogenous small RNAs and ncRNAs participating in these transcriptional regulatory networks might become valuable targets to modulate expression of genes involved in human diseases. Thus, understanding these basic processes of gene regulation might be translated in the near future into innovative therapeutic strategies to treat human diseases.

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One of the main challenges in the perspective of a hydrogen economy is the development of a storage system both safe and with high weight capacity. Among the most promising systems are the storage in metals and chemical hydrides and the high pressure storage in tanks made of composite materials. Both these technologies allow volumetric densities equal or higher than that of liquid hydrogen. The present work deals with the results obtained in a Italian national project, whose objectives have been the development of innovative technologies in specific applications: large scale energy storage, stationary applications in distributed generation, and automotive (with a particular attention to the fluvial and the sea transportation in protected areas). The theoretical, modellistic and experimental activities have been oriented to the development of innovative high capacity metal hydrides, the study of a regeneration method for chemical hydrides, the integration of intermediate pressure electrolyzers with advanced compressors and, finally, the development of thermomechanical models for executive design of storage systems. A number of prototypes has been realised and installed in a test facility in the Fusina (Venezia) power plant. The activity has been completed with an executive feasibility evaluation, in the perspective of industrial applications.

The fuel cell system and fuel cell gas turbine hybrid system represent an emerging technology for power generation because of its higher energy conversion efficiency, extremely low environmental pollution, and potential use of some renewable energy sources as fuels. Depending upon the type and size of applications, from domestic heating to industrial cogeneration, there are different types of fuel cell technologies to be employed. The fuel cells considered in this paper are mainly the molten carbonate (MCFC) and the solid oxide (SOFC) fuel cells, while a brief overview is provided about the proton exchange membrane (PEMFC). In all these systems, heat exchangers play an important and critical role in the thermal management of the fuel cell itself and the boundary components, such as the fuel reformer (when methane or natural gas is used), the air preheating, and the fuel cell cooling. In this paper, the impact of heat exchangers on the performance of SOFC, MCFC gas turbine hybrid systems and PEMFC systems is investigated. Several options in terms of cycle layout and heat exchanger technology are discussed from the on-design, off-design and control perspectives. A general overview of the main issues related to heat exchangers performance, cost and durability is presented and the most promising configurations identified.

This work describes different models, developed by the Thermochemical Power Group at the University of Genoa (Italy), for the simulation of solid oxide fuel cell and gas turbine hybrid systems. The paper focuses on both “cores” of the system: the fuel cell stack on the one hand and the turbomachinery and the auxiliaries on the other hand. Therefore, in the first part of the paper the models developed for the analysis of the Rolls‐Royce Integrated Planar SOFC cells are presented; the results are compared to experimental data, and carefully analysed and discussed. In the second part of the paper, design and off design models of IP‐SOFC pressurised hybrid systems in the range 250 kW–20 MW are presented; the hybrid performance results are presented and discussed, also taking ambient condition effects and a possible control strategy into account. Finally, using an in‐house general purpose transient system analysis code (TRANSEO code), where chemical composition, heat transfer, and fluid dynamic influences vs.time are considered in detail, a preliminary time dependent investigation of a pressurised hybrid system behaviour is presented.