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Humans are exposed to complex mixtures of mycotoxins through diet. Despite the serious threat they pose, mycotoxin risk assessment often overlooks co-exposure. With the aim of filling this gap, the present study investigates the combined cytotoxicity of sterigmatocystin (STE), ochratoxin A (OTA) and patulin (PAT) in human tumour Neuroblastoma and healthy Mesenchymal Stem Cells three-dimensional (3D) spheroids. The range of concentrations tested (1.56-50 μM for STE, 0.78-25 μM for OTA and 0.15-5 μM for PAT) was selected considering the IC 50 values obtained in previous studies and the estimated dietary exposure of consumers. To ensure appropriate experimental conditions, assessments for single mycotoxins and their combinations were conducted simultaneously. The nature of the toxicological interactions among the mycotoxins was then defined using the isobologram analysis. Our results demonstrated increased cytotoxicity in mycotoxin mixtures compared to individual exposure, with abundance of synergistic interactions. These findings highlight that the co-occurrence of STE, OTA and PAT in food may increase their individual toxic effects and should not be underestimated. Moreover, the use of advanced culture models increased the reliability and physiological relevance of our results which can serve as a groundwork for formulating standardized regulatory approaches towards mycotoxin mixtures in food and feed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Postoperative patients with ostomies experience significant changes in their lives as a result of the device implantation. Self-care is important to improve their health outcomes. Telehealth provides an opportunity to expand access to self-care education., Aim: This is a multicenter, non-inferiority randomized, open-label, controlled trial to evaluate the non-inferiority of a telehealth intervention to the standard in-person approach in improving self-care behaviors., Methods and Analysis: Three hundred and eighty-four patients aged ≥ 18 years, with a recently placed ostomy, no stomal/peristomal complications, and documented cognitive integrity will be randomly assigned (1:1) to receive either a telehealth intervention (four remote educational sessions) or a standard educational approach (four in-person sessions) delivered in outpatient settings. Every session (remote and in-person) will occur on Days 25, 32, 40, and 60 after discharge. Follow-ups will occur 1, 3, and 6 months after the last intervention session. Primary outcome is self-care maintenance measured using the Ostomy Self-care Index (OSCI). Secondary outcomes include self-care monitoring, self-care management, self-efficacy (OSCI), quality of life (Stoma specific quality of Life), depression (Patient Health Questionnaire-9), adjustment (Ostomy Adjustment Inventory-23), stomal and peristomal complication rates, healthcare services utilization, mobility, and number of working days lost. Analyses will be performed per intention-to-treat and per protocol., Ethics and Dissemination: This study has been approved by the Institutional Review Board of the main center (registration number: 119/22). Following completion of the trial, dissemination meetings will be held to share the results of the study with the participants and the health-care team. Adoption of telehealth technologies for ostomy patients can improve service organization by ensuring better integration and continuity of care. If the remote intervention produces comparable effects to the in-person intervention, it would be wise to make telehealth education an alternative treatment for addressing the educational needs of uncomplicated postoperative ostomy patients., Trial Registration: ClinicalTrials.gov (identifier number: NCT05796544)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Iovino et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The cobalt-catalyzed asymmetric hydrogenation of indazole-containing enamides relevant to the synthesis of the calcitonin gene-related peptide (CGRP) receptor antagonist, zavegepant ( 1 ), approved for the treatment of migraines, is described. Both neutral bis(phosphine)cobalt(II) and cationic bis(phosphine)cobalt(I) complexes served as efficient precatalysts for the enamide hydrogenation reactions, providing excellent yield and enantioselectivities (up to >99.9%) for a range of related substrates, though key reactivity differences were observed. Hydrogenation of indazole-containing enamide, methyl ( Z )-2-acetamido-3-(7-methyl-1 H -indazol-5-yl)acrylate, was performed on a 20 g scale.

Mycotoxins are secondary metabolites produced by filamentous fungi associated with a variety of acute and chronic foodborne diseases. Current toxicology studies mainly rely on monolayer cell cultures and animal models, which are undeniably affected by several limitations. To bridge the gap between the current in vitro toxicology approach and the in vivo predictability of the data, we here investigated the cytotoxic effects induced by the mycotoxins sterigmatocystin (STE), ochratoxin A (OTA) and patulin (PAT) on different 2D and 3D cell cultures. We focused on human tumours (neuroblastoma SH-SY5Y cells and epithelial breast cancer MDA-MB-213 cells) and healthy cells (bone marrow-derived mesenchymal stem cells, BM-MSC, and umbilical vein endothelial cells, HUVECs). The cytotoxicity of STE, OTA, and PAT was determined after 24, 48 and 72 h of exposure using an ATP assay in both culture models. Three-dimensional spheroids' morphology was also analysed using the MATLAB-based open source software AnaSP 1.4 version. Our results highlight how each cell line and different culture models showed specific sensitivities, reinforcing the importance of using more complex models for toxicology studies and a multiple cell line approach for an improved and more comprehensive risk assessment.

Current investigations in the field of toxicology mostly rely on 2D cell cultures and animal models. Although well-accepted, the traditional 2D cell-culture approach has evident drawbacks and is distant from the in vivo microenvironment. To overcome these limitations, increasing efforts have been made in the development of alternative models that can better recapitulate the in vivo architecture of tissues and organs. Even though the use of 3D cultures is gaining popularity, there are still open questions on their robustness and standardization. In this review, we discuss the current spheroid culture and organ-on-a-chip techniques as well as the main conceptual and technical considerations for the correct establishment of such models. For each system, the toxicological functional assays are then discussed, highlighting their major advantages, disadvantages, and limitations. Finally, a focus on the applications of 3D cell culture for mycotoxin toxicity assessments is provided. Given the known difficulties in defining the safety ranges of exposure for regulatory agency policies, we are confident that the application of alternative methods may greatly improve the overall risk assessment.

Here, we report real-world evidence on the safety and efficacy of nilotinib as a first-line treatment in elderly patients with chronic phase CML, treated in 18 Italian centers. Sixty patients aged > 65 years (median age 72 years (65-84)) were reported: 13 patients were older than 75 years. Comorbidities were recorded at baseline in 56/60 patients. At 3 months of treatment, all patients obtained complete hematological response (CHR), 43 (71.6%) an early molecular response (EMR), while 47 (78%) reached a complete cytogenetic response (CCyR). At last follow-up, 63.4% of patients still had a deep molecular response (MR4 or better), 21.6% reached MR3 as best response and 11.6% persisted without MR. Most patients (85%) started the treatment at the standard dose (300 mg BID), maintained at 3 months in 80% of patients and at 6 months in 89% of them. At the last median follow-up of 46.3 months, 15 patients discontinued definitively the treatment (8 due to side effects, 4 died for unrelated CML causes, 1 for failure, 2 were lost to follow-up). One patient entered in treatment-free remission. As to safety, 6 patients (10%) experienced cardiovascular events after a median time of 20.9 months from the start. Our data showed that nilotinib could be, as first-line treatment, effective and relatively safe even in elderly CML patients. In this setting, more data in the long term are needed about possible dose reduction to improve the tolerability, while maintaining the optimal molecular response., (© 2023. The Author(s).)

Background: Tumor hypoxia stimulates release of extracellular vesicles (EVs) that facilitate short- and long-range intercellular communication and metastatization. Albeit hypoxia and EVs release are known features of Neuroblastoma (NB), a metastasis-prone childhood malignancy of the sympathetic nervous system, whether hypoxic EVs can facilitate NB dissemination is unclear., Methods: Here we isolated and characterized EVs from normoxic and hypoxic NB cell culture supernatants and performed microRNA (miRNA) cargo analysis to identify key mediators of EVs biological effects. We then validated if EVs promote pro-metastatic features both in vitro and in an in vivo zebrafish model., Results: EVs from NB cells cultured at different oxygen tensions did not differ for type and abundance of surface markers nor for biophysical properties. However, EVs derived from hypoxic NB cells (hEVs) were more potent than their normoxic counterpart in inducing NB cells migration and colony formation. miR-210-3p was the most abundant miRNA in the cargo of hEVs; mechanistically, overexpression of miR-210-3p in normoxic EVs conferred them pro-metastatic features, whereas miR-210-3p silencing suppressed the metastatic ability of hypoxic EVs both in vitro and in vivo., Conclusion: Our data identify a role for hypoxic EVs and their miR-210-3p cargo enrichment in the cellular and microenvironmental changes favoring NB dissemination., (© 2023. The Author(s).)

Given the increasing importance of establishing better risk assessments for mycotoxins, novel in vitro tools for the evaluation of their toxicity are mandatory. In this study, an in vitro 3D spheroid model from SH-SY5Y cells, a human neuroblastoma cell line, was developed, optimized and characterized to test the cytotoxic effects caused by the mycotoxin sterigmatocystin (STE). STE induced a concentration- and time-dependent cell viability decrease in spheroids. Spheroids displayed cell disaggregation after STE exposure, increasing in a dose-dependent manner and over time. STE also induced apoptosis as confirmed by immunofluorescence staining and Western blot. Following the decreased proliferation and increased apoptosis, STE cytostasis effects were observed by migration assays both in 2D and 3D cell culture. Increased ROS generation, as well as DNA damage were also observed. Taken together, these data highlight the cytotoxic properties of STE and suggest that cell culture models play a pivotal role in the toxicological risk assessment of mycotoxins. The evaluation of cytotoxicity in spheroids (3D) rather than monolayer cultures (2D) is expected to more accurately reflect in vivo-like cell behaviour., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Healthcare rehabilitator skills can be grouped into hard and soft skills. Hard skills are specific and teachable, which can be defined and measured, while soft skills are less tangible and more difficult to quantify. The aim of this study is to investigate the level of knowledge of soft skills among Italian healthcare rehabilitators, and how they were acquired., Design and Methods: Two hundred healthcare rehabilitators, who worked in Southern Italy were enrolled from September 1st to October 31st 2017, and interviewed with Computer-Assisted-Web-Interview (CAWI) software, to assess their level of soft skills., Results: Healthcare rehabilitators showed significant satisfaction with university education (59.5%), particularly for theoretical training (64%), while significant dissatisfaction was found for technical-practical training (63.5%), training in patients' family management (66.5%) and stages participation to improve soft skills (59%). Dissatisfied rehabilitators were found for university education of soft skills (59%), particularly for interpersonal relationships with patients family (66.5%) and technical-practical train in(63.5%). Women considered the training courses about soft skills acquisition more useful than men (43.8%)., Conclusions: Healthcare rehabilitator training is lacking in the teaching of both technical-practical and soft skills. It is striking that in a healthcare profession like that of the rehabilitator, where practical and empathic skills are fundamental in the relationship with the patients, such skills are not treated in analogously with theoretical training.

Neuroblastoma is an embryonal malignancy of early childhood arising from the embryonic sympatho-adrenal lineage of the neural crest. About half of all cases are currently classified as high-risk of disease recurrence, with an overall survival rate of less than 40% at 5 years despite intensive therapy. Recent studies on matched primary tumours and at the relapse revealed downregulation of genes transcriptionally silenced by YAP as significant association with neuroblastoma relapse. Here, we evaluated the pharmacological targeting of YAP/TAZ with the YAP/TAZ-TEAD inhibitor Verteporfin (VP) in Tumour Initiating Cells (TICs) derived from High-Risk Neuroblastoma patients. VP treatment suppresses YAP/TAZ expression, induces apoptosis and causes the re-organization of the cytoskeleton reducing cells migration and clonogenic ability. Moreover, VP reduces the percentage of side population cells and ABC transporters involved in drug resistance, and the percentage of stem cell subpopulations CD133+ and CD44 + of TICs. Finally, we demonstrated that VP sensitizes TICs to the standard drugs used for neuroblastoma therapy etoposide and cis-platin opening the way to use VP as drug repositioning candidate for recurrent neuroblastoma., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background/aim: In oncological settings, high-quality decision-making takes place when an adaptive pattern of cognitive and behavioural processes occurs, potentially limiting post-decisional regret and leading to an increment of adherence to the final decision. An example of a choice that requires a patient's involvement in the decision-making during cancer treatment occurs when the insertion of Central Vascular Access Device (CVAD) is proposed for chemotherapy administration. The aim of the current study was to develop and evaluate the psychometric properties of an Italian version of the Decisional Conflict Scale (DCS), including its factorial structure and its accuracy in discriminating the level of uncertainty in a sample of cancer patients during their decision-making process for the insertion of a CVAD for intravenous (IV) chemotherapy administration., Materials and Methods: The study included 264 cancer patients with different diagnoses. To test the structural and psychometric properties of the Italian version of the DCS (DCS-ITA), exploratory factorial analysis was conducted followed by traditional classical test theory assessments of internal reliability and criterion validity., Results: The Italian version of the DCS (DCS-ITA) demonstrated good internal consistency, acceptable construct validity, which was tested with exploratory factorial analysis, and good criterion validity, demonstrated by the ability of the scale to differentiate between patients who declared themselves certain about their choice and patients expressing uncertainty about the choice to make., Conclusion: Overall, the results of the study showed that the DCS-ITA is a psychometrically sound instrument that easily discriminates between patients who are experiencing a decisional conflict and those who are not. The DCS-ITA can be used as a valid and easy-to-use tool for the screening of the decisional conflict in oncological settings., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background and Objectives: Game addiction is an emerging problem in public health. A gaming disorder is characterized by a pattern of persistent or recurrent gaming behavior. The behavioral pattern is severe enough to implicate a significant involvement of family, social, educational, professional, or other relationships. Therefore, greater attention needs to be paid to potential addictive behaviors in terms of video games in order to identify both pre-adolescents and adolescents at risk and to provide them with adequate assistance. Materials and Methods : A random sample of 622 students including pre-adolescents and adolescents were enrolled from September 1st to October 31th 2016, and the Game Addiction Scale (GAS) interview was used to identify pathological students with both Monothetic and Polythetic analysis., Results: This study shows the presence of pathological students is equal to 1.93%, with 37.46% and 4.50% obtained with Monothetic and Polythetic analysis (global and partial), respectively. In our sample, the most frequent were students with a gaming time of 1 or 2 h, and students with a day gaming frequency of 1, 2, or 3 times a day. The items with more pathological students were Item 2 (i.e., Tolerance) and 4 (i.e., Withdrawal). Every item was positively correlated with Daily gaming time(hours) and Daily game frequency, excluding Item 4(i.e., Withdrawal). Finally, the Monothetic GAS score was positively correlated with Daily gaming time while the Polythetic Global GAS was positively correlated with Daily game frequency and negatively with Education level; instead, the Polythetic Partial GAS score was positively correlated with only Daily gaming time., Conclusion: Males are pathological gamblers more so than females and spend more time playing video games. An increase in Daily game frequency or Daily gaming time implicates an increase in video game addictions, while an increase in Education level, which generally corresponds to a greater age, implicates a decrease in game addiction. Finally, we observed that the correlations obtained between the Polythetic Partial GAS score with the independent variables such as Age, Gender, Education level, Daily gaming time (hours), and Daily game frequency were analogous to the significant correlations obtained with the Monothetic GAS score, while these correlations were different for the Polythetic Global GAS and the independent variables. These results suggest that the use of the original Polythetic scale should not be neglected., Competing Interests: The authors declare no conflicts of interest.

Background: The management of chronic diseases, particularly in children, requires an integrated physical and psychological approach to both sick children and their family. This is the case of Cystic Fibrosis (CF), a complex genetic chronic disease, where, a comprehensive evaluation of the emotional impact and an effective multidimensional approach are indicated., Aim: This study investigates on parenting stress in children and adolescents with CF and its determinants related to parents, children and the disease severity., Methods: The study involved 34.04% adult males and 65.96% adult females (range 21-55 years) and 47 children with CF, 54.35% males and 45.65% females (range 1-17 years). The data were obtained through a Parenting Stress Index - Short Form (PSI-SF) questionnaire. According to the PSI-SF scoring system, three types of stress were detected: a typical stress pattern (normal), a high stress pattern (increased) and a defensive response, which may be considered as a high stress feature in children which requires monitoring and clinical evaluation., Results: This study shows a significant presence of stress in females (60.23%), of subject married (84.62%), unemployed (69.23%) and with education level such as "middle School" (61.54%). Concerning children of parents with high stress, it resulted most frequent children with one sibling (53.85%). Finally, by univariate analysis, it resulted a significant positive correlation between parenting stress and disease degree of children. Instead by multivariate analysis, we found that the variables: Number of siblings and Birth order were a significant positive and negative predictor of parenting stress respectively., Conclusion: An increased stress level was detected in less than one third of parents of subjects with CF. These data may be related to the psychological support which is part of the routine management of CF care team. However, as children's features seem to act as a determinant of stress more than parental ones, the parental-child dysfunction should be the target for further integrated interventions.

Background: Neuroblastoma (NB) is a paediatric tumour of the sympathetic nervous system. Half of all cases are defined high-risk with an overall survival less than 40% at 5 years from diagnosis. The lack of in vitro models able to recapitulate the intrinsic heterogeneity of primary NB tumours has hindered progress in understanding disease pathogenesis and therapy response., Methods: Here we describe the establishment of 6 patient-derived organoids (PDOs) from cells of NB tumour biopsies capable of self-organising in a structure resembling the tissue of origin., Results: PDOs recapitulate the histological architecture typical of the NB tumour. Moreover, PDOs expressed NB specific markers such as neural cell adhesion molecules, NB84 antigen, synaptophysin (SYP), chromogranin A (CHGA) and neural cell adhesion molecule NCAM (CD56). Analyses of whole genome genotyping array revealed that PDOs maintained patient-specific chromosomal aberrations such as MYCN amplification, deletion of 1p and gain of chromosome 17q. Furthermore, the PDOs showed stemness features and retained cellular heterogeneity reflecting the high heterogeneity of NB tumours., Conclusions: We were able to create a novel preclinical model for NB exhibiting self-renewal property and allowing to obtain a reservoir of NB patients' biological material useful for the study of NB molecular pathogenesis and to test drugs for personalised treatments.

Background: Cancer is the leading cause of death worldwide. Of the various therapeutic approaches, chemotherapy is the most widely used treatment. Among the various side effects associated with this treatment, taste alterations (TAs) have received little attention, even though they have a serious impact on the nutritional aspect and quality of life (QoL) of patients. TAs concern 75% of the patients receiving chemotherapy, and this figure is still considered to be underestimatedbeacuse could be due both to inadequate attention and to the absence of specific subjective tools able to fully evaluate TAs in patients undergoing chemotherapy., Methods: A review by querying CINAHL, PubMed, Scopus and Google Scholar databases about the current status of use of the CiTAS self-evaluation scale, was performed., Results: From critical reading of the selected reports, it can be said that until now CiTAS has not been used to a large extent for evaluating taste, even at a late stage in patients undergoing chemotherapy. However, the results and the selected reports seem to indicate hope for its wider use., Conclusions: In literature, CITAS scale has been used on very heterogeneous populations and not adequately studied in specific care settings, its use within controlled trials could implement its spread.Correct and subjective evaluation of TAs would allow the planning of specific and personalized interventions aimed at providing adequate nutrition to support the maintenance and/or achievement of a correct body mass index. All this could contribute significantly to a better perception of QoL in patients undergoing chemotherapy.

Introduction: Paediatric delirium is associated with a longer duration of hospitalization in paediatric intensive care units, the emergence of post-traumatic symptoms and possible neurocognitive dysfunction after discharge. In preschool children, the diagnosis of delirium appears rather challenging: their pre-verbal status and the presence of cognitive skills still in development make accurate diagnosis difficult. Recently, a pediatric delirium screening tool suitable for critical preschool children has also been developed and identified in international literature, with excellent results also in critical infants under 2 years of age: the Cornell Assessment of Pediatric Delirium (CAPD). The CAPD, using a Likert scale, bases the assessment of paediatric delirium within the context of child development. This scale follows the development of the infant by comparing the detection of specific items on the scale as the anchor points that characterize the development of infants by age groups., Objective: Culturally and linguistically validation in Italian language and prior testing of the Cornell Assessment of Pediatric Delirium., Method: Translation and Cultural Validation of the Cornell Assessment of Pediatric Delirium (CAPD) for the Evaluation/Diagnosis of Pediatric Delirium within Pediatric Intensive Care. The translation and adaptation of this instrument followed the phases of the model proposed by the World Health Organization. Prior testings, such as item descriptive analysis, item-total correlation and Cronbach's alpha, were conducted., Results: All phases of the cultural-linguistic validation process were carried out in a satisfactory manner. For the prior testing, the scale was administered to a sample of 42 children, with age ranged 0-5 years old (66.6%), with a higher prevalence of the male gender. All items were normally distributed and there was no excessive Skeweness and Kurtosis. Each item contributed to the scale fairly well and all coefficients of item total correlation (rjx) were higher than the recommended level of 0.30. The composite reliability index was 0.94 and Cronbach's alpha was 0.96., Conclusions: The process has meticulously followed the recommendations in international literature. The final version was approved by the authors of the original instrument.

Neuroblastoma is a neural crest-derived tumor that accounts for 7-10% of all malignancies in children and ~15% of all childhood cancer-associated mortalities. Approximately 50% of patients are characterized as high-risk (HR) and have an overall survival of <40% at 5 years from diagnosis. HR patients with unfavorable prognosis exhibit several structural copy number variations (CNVs), whereas localized tumors belonging to patients in the low- and intermediate-risk classes, have favorable outcomes and display several numerical CNVs. Taken together these results are indicative of chromosome instability (CIN) in neuroblastoma tumor cells. The present review discusses multiple aspects of CIN including methods of measuring CIN, CIN targeting as a therapeutic strategy in cancer and the effects of CIN in neuroblastoma development and aggressiveness with particular emphasis on the CIN gene signature associated with HR neuroblastoma patients.

Neuroblastoma (NB) is an embryonic malignancy of the sympathetic nervous system with heterogeneous biological, morphological, genetic and clinical characteristics. Although genomic studies revealed the specific biological features of NB pathogenesis useful for new therapeutic approaches, the improvement of high-risk (HR)-NB patients overall survival remains unsatisfactory. To further clarify the biological basis of disease aggressiveness, we used whole-exome sequencing to examine the genomic landscape of HR-NB patients at stage M with short survival (SS) and long survival (LS). Only a few genes, including SMARCA4, SMO, ZNF44 and CHD2, were recurrently and specifically mutated in the SS group, confirming the low recurrence of common mutations in this tumor. A systems biology approach revealed that in the two patient groups, mutations occurred in different pathways. Mutated genes (ARHGEF11, CACNA1G, FGF4, PTPRA, PTK2, ANK3, SMO, NTNG2, VCL and NID2) regulate the MAPK pathway associated with the organization of the extracellular matrix, cell motility through PTK2 signaling and matrix metalloproteinase activity. Moreover, we detected mutations in LAMA2, PTK2, LAMA4, and MMP14 genes, impairing MET signaling, in SFI1 and CHD2 involved in centrosome maturation and chromosome remodeling, in AK7 and SPTLC2, which regulate the metabolism of nucleotides and lipoproteins, and in NALCN, SLC12A1, SLC9A9, which are involved in the transport of small molecules. Notably, connected networks of somatically mutated genes specific for SS patients were identified. The detection of mutated genes present at the onset of disease may help to address an early treatment of HR-NB patients using FDA-approved compounds targeting the deregulated pathways., (© 2018 UICC.)

Exchange of information between healthcare professionals involved in the care of patients is essential for providing effective care. Use of the Situation-BackgroundAssessment-Recommendation (SBAR) methodology is increasingly indicated in the health sector to facilitate communication during handovers of patients between clinicians or clinical teams. The present review of the literature aims to determine the effectiveness of the SBAR methodology in the handover of nursing documentation.

The objectives of the cross-sectional study were to delineate the knowledge, attitudes, and behavior among nurses regarding the prevention of central line-associated bloodstream infections (CLABSIs) and to identify their predisposing factors. A questionnaire was self-administered from September to November 2011 to nurses in oncology and outpatient chemotherapy units in 16 teaching and non-teaching public and private hospitals in the Campania region (Italy). The questionnaire gathered information on demographic and occupational characteristics; knowledge about evidence-based practices for the prevention of CLABSIs; attitudes towards guidelines, the risk of transmitting infections, and hand-washing when using central venous catheter (CVC); practices about catheter site care; and sources of information. The vast majority of the 335 nurses answered questions correctly about the main recommendations to prevent CLABSIs (use sterile gauze or sterile transparent semipermeable dressing to cover the catheter site, disinfect the needleless connectors before administer medication or fluid, disinfect with hydrogen peroxide the catheter insertion site, and use routinely anticoagulants solutions). Nurses aged 36 to 50 years were less likely to know these main recommendations to prevent CLABSIs, whereas this knowledge was higher in those who have received information about the prevention of these infections from courses. Nurses with lower education and those who do not know two of the main recommendations on the site's care to prevent the CLABSIs, were more likely to perceive the risk of transmitting an infection. Higher education, attitude toward the utility allow to dry antiseptic, and the need of washing hands before wearing gloves for access to port infusion were predictors of performing skin antiseptic and aseptic technique for dressing the catheter insertion site. Educational interventions should be implemented to address the gaps regarding knowledge and practice regarding the prevention of CLABSIs and to ensure that nurses use evidence-based prevention interventions.

Neuroblastoma is an embryonic malignancy of early childhood originating from neural crest cells and showing heterogeneous biological, morphological, genetic and clinical characteristics. The correct stratification of neuroblastoma patients within risk groups (low, intermediate, high and ultra-high) is critical for the adequate treatment of the patients.High-throughput technologies in the Omics disciplines are leading to significant insights into the molecular pathogenesis of neuroblastoma. Nonetheless, further study of Omics data is necessary to better characterise neuroblastoma tumour biology. In the present review, we report an update of compounds that are used in preclinical tests and/or in Phase I-II trials for neuroblastoma. Furthermore, we recapitulate a number of compounds targeting proteins associated to neuroblastoma: MYCN (direct and indirect inhibitors) and downstream targets, Trk, ALK and its downstream signalling pathways. In particular, for the latter, given the frequency of ALK gene deregulation in neuroblastoma patients, we discuss on second-generation ALK inhibitors in preclinical or clinical phases developed for the treatment of neuroblastoma patients resistant to crizotinib.We summarise how Omics drive clinical trials for neuroblastoma treatment and how much the research of biological targets is useful for personalised medicine. Finally, we give an overview of the most recent druggable targets selected by Omics investigation and discuss how the Omics results can provide us additional advantages for overcoming tumour drug resistance.

Neuroblastoma (NB) is a threatening childhood malignancy. Its prognosis is affected by several morphological, and biological characteristics, including the constitutive expression of ALK tyrosine kinase. In this study we examined the therapeutic potential of a novel ALK inhibitor, entrectinib, in obliterating NB tumor cells. Entrectinib showed the growth-inhibitory effects on NB cells with a 50% inhibitory concentration range of 0.03-5 μM. In the ALK-dependent cells, entrectinib mediated G1-arrest, which was associated with modified expression of multiple cell-cycle regulators. Down-regulation of Ki-67, and attenuated phosphorylation of ERK1/2, and STAT3, correlated with observed antiproliferative capacity of entrectinib. Initial cytostatic activity of entrectinib was followed by concentration-dependent apoptotic cell death, and Caspase-3 activation. However, we delineated a reduced sensitivity of ALK mutated NB cells to entrectinib, and demonstrated strong activation of autophagy in SH-SY5YF1174L NB cell line. Abrogation of autophagy by chloroquine increased significantly the toxicity of entrectinib, as confirmed by enhanced death rate, and PARP protein cleavage in SH-SY5YF1174L cells. In aggregate, our data show that entrectinib inhibits proliferation, and induces G1-arrest, and apoptosis in NB cells. We propose entrectinib for further consideration in treatment of NB, and recommend pharmacological inhibition of autophagy to be explored for a combined therapeutic approach in NB patients that might develop resistance to entrectinib.

Background: Less than 5% of neuroblastomas (NB) occur in adolescents and young adults (AYA), in whom the disease has an indolent and fatal course., Procedure: We studied the genomic profile and histological characteristics of 34 NBs from AYA patients enrolled in the Italian Neuroblastoma Registry (INBR) between 1979 and 2009., Results: Disease was disseminated in 20 patients and localized in 14; 30/34 tumors were classified as NB and 4/34 as nodular ganglioneuroblastoma (nGNB). Segmental Chromosome Aberrations (SCAs) were observed in 29 tumors (85%) namely 1p imbalance (58%), 17q gain (52%), 9p loss (32%), 11q loss (30%), 1q gain (17%), 7q gain (17%), 2p gain (14%), 3p loss (14%), and 4p loss (7%). MYCN amplification and MYCN gain were detected in 3 (10%) and 2 cases (7%) respectively. An anaplastic lymphoma receptor tyrosine kinase (ALK) gene mutation study on the available cases from this cohort revealed 4/25 (16%) mutated cases. In parallel, alpha thalassaemia/mental retardation syndrome X linked (ATRX) gene mutations were also sought, a novel mutation being detected in 1/21 (4,7%) cases., Conclusion: This study confirmed the low incidence of MYCN amplification in AYA and recorded a high frequency of 17q gain and 9p and 11q loss independently from the stage of the disease. The presence of 1q gain, which identifies patients with particularly aggressive disease, relapse and poor survival, was also detected. Furthermore, the frequency of ALK mutations suggests that a target-based therapy with ALK inhibitors might be effective in this subset of patients., (© 2015 Wiley Periodicals, Inc.)

To get insights on the metastatic process of human neuroblastoma (NB), the miRNA expression profile of bone marrow (BM)-infiltrating cells has been determined and compared to that of primary tumors.Twenty-two BM-infiltrating cells, 22 primary tumors, and 4 paired samples from patients with metastatic NB aged > 12 months were analyzed for the expression of 670 miRNAs by stem-loop RT-qPCR. The miRNAs whose expression was significantly different were subjected to selection criteria, and 20 selected miRNAs were tested in 10 additional BM-infiltrating cells and primary tumors. Among the miRNAs confirmed to be differentially expressed, miR-659-3p was further analyzed. Transfection of miR-659-3p mimic and inhibitor demonstrated the specific suppression and over-expression, respectively, of the miR-659-3p target gene CNOT1, a regulator of transcription of genes containing AU-rich element (ARE) sequence. Among the ARE-containing genes, miR-659-3p mimic and inhibitor specifically modified the expression of AKT3, BCL2, CYR61 and THSB2, belonging to the focal adhesion pathway. Most importantly, in BM-infiltrating cells CNOT1 expression was significantly higher, and that of AKT3, BCL2, THSB2 and CYR61 was significantly lower than in primary tumors. Thus, our study suggests a role of the focal adhesion pathway, regulated by miR-659-3p through CNOT1, in the human NB metastatic process.

Congenital dyserythropoietic anemia type II, a recessive disorder of erythroid differentiation, is due to mutations in SEC23B, a component of the core trafficking machinery COPII. In no case homozygosity or compound heterozygosity for nonsense mutation(s) was found. This study represents the first description of molecular mechanisms underlying SEC23B hypomorphic genotypes by the analysis of five novel mutations. Our findings suggest that reduction of SEC23B gene expression is not associated with CDA II severe clinical presentation; conversely, the combination of a hypomorphic allele with one functionally altered results in more severe phenotypes. We propose a mechanism of compensation SEC23A-mediated which justifies these observations., (Copyright © 2013 Elsevier Inc. All rights reserved.)