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Senataxin is an evolutionarily conserved DNA/RNA helicase, whose dysfunctions are linked to neurodegeneration and cancer. A main activity of this protein is the removal of R-loops, which are nucleic acid structures capable to promote DNA damage and replication stress. Here we found that Senataxin deficiency causes the release of damaged DNA into extranuclear bodies, called micronuclei, triggering the massive recruitment of cGAS, the apical sensor of the innate immunity pathway, and the downstream stimulation of interferon genes. Such cGAS-positive micronuclei are characterized by defective membrane envelope and are particularly abundant in cycling cells lacking Senataxin, but not after exposure to a DNA breaking agent or in absence of the tumor suppressor BRCA1 protein, a partner of Senataxin in R-loop removal. Micronuclei with a discontinuous membrane are normally cleared by autophagy, a process that we show is impaired in Senataxin-deficient cells. The formation of Senataxin-dependent inflamed micronuclei is promoted by the persistence of nuclear R-loops stimulated by the DSIF transcription elongation complex and the engagement of EXO1 nuclease activity on nuclear DNA. Coherently, high levels of EXO1 result in poor prognosis in a subset of tumors lacking Senataxin expression. Hence, R-loop homeostasis impairment, together with autophagy failure and unscheduled EXO1 activity, elicits innate immune response through micronuclei formation in cells lacking Senataxin., (© 2024. The Author(s).)

Background and Aim: Resveratrol (RSV), is a stilbene-based compound exerting wide biological properties. Its analogue 4,4'-dihydroxy- trans -stilbene (DHS) has shown improved bioavailability and antiproliferative activity in vitro and in vivo . One of the hypotheses on how resveratrol works is based on SIRT1 activation. Since their strict structural similarities, we have explored a potential interaction between DHS and SIRT1, in comparison with the parental molecule., Experimental Procedure: Timing of incubation and concentrations of DHS have been determined using MTT assay in normal human lung fibroblasts. Untreated, DHS- or RSV-treated cells were harvested and analysed by Western Blotting or RT-PCR, in order to evaluate SIRT1 levels/activity and expression, and by Cellular Thermal shift assay (CETSA) to check potential DHS or RSV-SIRT1 interaction. Transfection experiments have been performed with two SIRT1 mutants, based on the potential binding pockets identified by Molecular Docking analysis., Results and Conclusion: We unexpectedly found that DHS, but not RSV, exerted a time-dependent inhibitory effect on both SIRT1 protein levels and activity, the latter measured as p53 acetylation. At the mRNA level no significant changes were observed, whereas a proteasome-dependent mechanism was highlighted for the reduction of SIRT1 levels by DHS in experiments performed with the proteasome inhibitor MG132. Bioinformatics analysis suggested a higher affinity of RSV in binding all SIRT1 complexes compared to DHS, except comparable results for complex SIRT1-p53. Nevertheless, both CETSA and SIRT1 mutants transfected in cells did not confirm this interaction. In conclusion, DHS reduces SIRT1 protein level, thereby inhibiting its activity through a proteasome-mediated mechanism., Competing Interests: The authors declare no conflict of interest., (© 2024 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.)

Background: Sexual dimorphism represents a key concept in the comprehension of molecular processes guiding several sex-specific physiological and pathological mechanisms. It has been reported that genes involved in many disorders show a sex-dependent expression pattern. Moreover, the loss of Y chromosome (LOY), found to be a physiological age-driven phenomenon, has been linked to many neurodegenerative and autoimmune disorders, and to an increased cancer risk. These findings drove us towards the consideration that LOY may cause the de-regulation of disease specific networks, involving genes located in both autosomal and sex chromosomes., Results: Exploiting the CRISPR/Cas9 and RNA-sequencing technologies, we generated a Y-deficient human cell line that has been investigated for its gene expression profile. Our results showed that LOY can influence the transcriptome displaying relevant enriched biological processes, such as cell migration regulation, angiogenesis and immune response. Interestingly, the ovarian follicle development pathway was found enriched, supporting the female-mimicking profile of male Y-depleted cells., Conclusion: This study, besides proposing a novel approach to investigate sex-biased physiological and pathological conditions, highlights new roles for the Y chromosome in the sexual dimorphism characterizing human health and diseases. Moreover, this analysis paves the way for the research of new therapeutic approaches for sex dimorphic and LOY-related diseases., (© 2024. The Author(s).)

Females have a lower probability to develop somatic cancers and a better response to chemotherapy than males. However, the reasons for these differences are still not well understood. The X-linked gene TSPY-Like 2 (TSPYL2) encodes for a putative tumor suppressor protein involved in cell cycle regulation and DNA damage response (DDR) pathways. Here, we demonstrate that in unstressed conditions TSPYL2 is maintained at low levels by MDM2-dependent ubiquitination and proteasome degradation. Upon genotoxic stress, E2F1 promotes TSPYL2 expression and protein accumulation in non-transformed cell lines. Conversely, in cancer cells, TSPYL2 accumulates only in females or in those male cancer cells that lost the Y-chromosome during the oncogenic process. Hence, we demonstrate that while TSPYL2 mRNA is induced in all the tested tumor cell lines after DNA damage, TSPYL2 protein stability is increased only in female cancer cells. Indeed, we found that TSPYL2 accumulation, in male cancer cells, is prevented by the Y-encoded protein SRY, which modulates MDM2 protein levels. In addition, we demonstrated that TSPYL2 accumulation is required to sustain cell growth arrest after DNA damage, possibly contributing to protect normal and female cancer cells from tumor progression. Accordingly, TSPYL2 has been found more frequently mutated in female-specific cancers. These findings demonstrate for the first time a sex-specific regulation of TSPYL2 in the DDR of cancer cells and confirm the existence of sexual dimorphism in DNA surveillance pathways., (© 2023. The Author(s).)

In the past decades, the expanding use of prostate-specific membrane antigen (PSMA) imaging for prostate cancer has led to the incidental detection of a lot of extra-prostatic malignancies showing an increased uptake of PSMA. Due to these incidental findings, the increasing amount of immunohistochemistry studies and the deeper knowledge of the mechanisms of expression of this antigen, it is now clear that "PSMA" is a misnomer, since it is not specific to the prostate gland. Nevertheless, this lack of specificity could represent an interesting opportunity to bring new insights on the biology of PSMA and its sites of expression to image and treat new conditions, particularly several cancers. In this review, we will describe the main extra-prostatic cancers that exhibit PSMA expression and that can be studied with PSMA-based positron emission tomography-computed tomography (PET/CT) as an additional or alternative tool to conventional imaging. In particular, we will focus on cancers in which a radioligand therapy with 177 lutetium has been attempted, aiming to provide an overview of the possible future theragnostic applications of PSMA.

Cancer incidence and survival are different between men and women. Indeed, females have a lesser risk and a better prognosis than males in many tumors unrelated to reproductive functions. Although the reasons for these disparities are still unknown, they constitute an important starting point for the development of personalized cancer therapies. One of the mechanisms that fuels carcinogenesis is the accumulation of defects in DNA damage response (DDR) pathways, a complex signaling cascade that senses DNA lesions and, depending on the severity, coordinates transient cell-cycle arrest, DNA replication, repair, apoptosis, and senescence, preventing genomic instability and cancer. Recently, evidence of sexual dimorphisms is emerging in these pathways, therefore providing new opportunities for precision medicine. Here, we will discuss current knowledge about sexual disparities in the DDR, their role in tumorigenesis and cancer progression, and the importance of considering sex contribution in both research and cancer therapies., Competing Interests: The authors declare no competing interest, (© 2022 The Author(s).)

Background: Nursing students' perception of a safe clinical working environment may impact the development of professional skills and progression in the profession., Purpose: The aims of this study were to describe to what extent nursing students perceive the working environments as safe during their most recent clinical rotation and to explore factors associated with their perception of a safe workplace environment., Methods: A nationwide Italian cross-sectional study involving 9607 students in 27 universities across 95 three-year nursing programs was performed in 2015-2016, and secondary analyses were run in 2019., Results: The workplace environment was perceived by students as only a little (n = 2598 [27.0%]), to some extent (n = 4048 [42.1%]), and always (n = 2555 [26.0%]) safe; 406 (4.2%) students reported to have never felt that the workplace as safe. At the multivariate level, factors promoting students' perception of a safe clinical environment were a setting offering higher (a) learning opportunities, (b) safety and nursing care quality, (c) quality of tutorial strategies, and (d) self-directed learning opportunities., Conclusions: Nursing faculty should assess the quality of clinical settings before deciding on environments for students' learning experience.

Purpose: To explore nursing students' perceptions of their clinical learning experiences in the mental health (MH) setting., Design and Methods: Secondary analysis of data collected within an Italian national cross-sectional study involving students (N = 9607) who were attending 95 3-year baccalaureate nursing programs., Findings: Students in MH settings scored the quality of the learning environment overall significantly higher (P = .008) compared to those who rotated in other clinical settings, specifically with respect to (a) the tutorial strategies' quality; (b) the learning opportunities; and (c) the learning environment's quality., Practice Implications: MH settings emerged as a worthy clinical environment where less pressing rhythms allow preceptors to provide students more learning opportunities that, in turn, affect the perceived degree of competence achieved and the desire to work in these contexts after graduation., (© 2019 Wiley Periodicals, Inc.)

Background: Nursing students report care of the older people as an undesirable career pathway. Positive clinical placement experiences influence students' attitudes and career intentions with respect to nursing home (NH) setting. The clinical environment's quality depends on meaningful learning opportunities, the relationship with the preceptors, and the pedagogical atmosphere as influenced by the staff-student interactions., Aim: The aim of this study was to explore nursing students' perceptions on their clinical learning experience and competence learned in the NH setting as compared to other clinical areas., Methods: A secondary analysis was performed of an Italian national cross-sectional study involving 9,607 nursing students attending 95 different three-year bachelor laureate nursing programmes in 27 universities. A questionnaire exploring individual and nursing programme variables was devised. Moreover, students self-reported the perceived quality of the clinical learning experience using the Clinical Learning Quality Evaluation Index tool and the degree of competence learned using a four-point Likert-type scale., Results: Students in the NH setting scored the overall quality of the learning environment significantly higher (p = 0.046) compared to those experiencing other clinical settings, and they scored higher learning occasions (p = 0.002) and self-directed learning opportunities (p = 0.018). No difference emerged in the perceived mean degree of competences learned at the end of the clinical rotation (p = 0.271)., Conclusion: Nursing students perceive the NH setting to be a good quality learning environment with valuable learning opportunities and self-directed learning opportunities compared to other settings. The nursing home setting provides opportunities to acquire clinical competences comparable to the ones in other clinical settings such as hospital units., Implications for Practice: Nursing home settings should be considered by all nursing programmes as a learning environment particularly worthy for students at different levels of their education., (© 2019 John Wiley & Sons Ltd.)

Background: In the last decade, the family system has changed significantly. Although in the past, older people used to live with their children, nowadays, they cannot always depend on assistance of their relatives. Many older people wish to remain as independent as possible while remaining in their homes, even when living alone. To do so, there are many tasks that they must perform to maintain their independence in everyday life, and above all, their well-being. Information and communications technology (ICT), particularly robotics and domotics, could play a pivotal role in aging, especially in contemporary society, where relatives are not always able to accurately and constantly assist the older person., Objective: The aim of this study was to understand the needs, preferences, and views on ICT of some prefrail older people who live alone. In particular, we wanted to explore their attitude toward a hypothetical caregiver robot and the functions they would ask for., Methods: We designed a qualitative study based on an interpretative phenomenological approach. A total of 50 potential participants were purposively recruited in a big town in Northern Italy and were administered the Fried scale (to assess the participants' frailty) and the Mini-Mental State Examination (to evaluate the older person's capacity to comprehend the interview questions). In total, 25 prefrail older people who lived alone participated in an individual semistructured interview, lasting approximately 45 min each. Overall, 3 researchers independently analyzed the interviews transcripts, identifying meaning units, which were later grouped in clustering of themes, and finally in emergent themes. Constant triangulation among researchers and their reflective attitude assured trustiness., Results: From this study, it emerged that a number of interviewees who were currently using ICT (ie, smartphones) did not own a computer in the past, or did not receive higher education, or were not all young older people (aged 65-74 years). Furthermore, we found that among the older people who described their relationship with ICT as negative, many used it in everyday life. Referring to robotics, the interviewees appeared quite open-minded. In particular, robots were considered suitable for housekeeping, for monitoring older people's health and accidental falls, and for entertainment., Conclusions: Older people's use and attitudes toward ICT does not always seem to be related to previous experiences with technological devices, higher education, or lower age. Furthermore, many participants in this study were able to use ICT, even if they did not always acknowledge it. Moreover, many interviewees appeared to be open-minded toward technological devices, even toward robots. Therefore, proposing new advanced technology to a group of prefrail people, who are self-sufficient and can live alone at home, seems to be feasible., (©Katia Daniele, Maura Marcucci, Cesarina Cattaneo, Nunzio Alberto Borghese, Lucia Zannini. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 06.08.2019.)

Protein acetylation and deacetylation events are finely regulated by lysine-acetyl-transferases and lysine-deacetylases and constitute an important tool for the activation or inhibition of specific cellular pathways. One of the most important lysine-acetyl-transferases is p300, which is involved in the regulation of gene expression, cell growth, DNA repair, differentiation, apoptosis, and tumorigenesis. A well-known target of p300 is constituted by the tumor suppressor protein p53, which plays a critical role in the maintenance of genomic stability and whose activity is known to be controlled by post-translational modifications, among which acetylation. p300 activity toward p53 is negatively regulated by the NAD-dependent deacetylase SIRT1, which deacetylates p53 preventing its transcriptional activation and the induction of p53-dependent apoptosis. However, the mechanisms responsible for p53 regulation by p300 and SIRT1 are still poorly understood. Here we identify the nucleosome assembly protein TSPY-Like 2 (TSPYL2, also known as TSPX, DENTT, and CDA1) as a novel regulator of SIRT1 and p300 function. We demonstrate that, upon DNA damage, TSPYL2 inhibits SIRT1, disrupting its association with target proteins, and promotes p300 acetylation and activation, finally stimulating p53 acetylation and p53-dependent cell death. Indeed, in response to DNA damage, cells silenced for TSPYL2 were found to be defective in p53 activation and apoptosis induction and these events were shown to be dependent on SIRT1 and p300 function. Collectively, our results shed new light on the regulation of p53 acetylation and activation and reveal a novel TSPYL2 function with important implications in cancerogenesis.

Background: Effective performance of clinical handovers should be one of the priorities of nursing education to promote efficient communication skills and ensure patient safety. However, to date, no studies have explored to what extent nursing students are involved in handovers., Objective: To explore nursing students' handover involvement during their clinical rotations and associated factors., Method: This was a secondary analysis of a large national cross-sectional study that involved 9607 undergraduate nursing students in 27 universities across 95 three-year Italian baccalaureate nursing programs. The involvement in the clinical handovers was the end point (from 0, never, to 3, always). A path analysis was performed to identify variables directly and indirectly affecting students' handover involvement., Results: Handover involvement was reported as 'only a little', 'to some extent', and 'always' by 1739 (18.1%), 2939 (30.6%), and 4180 (43.5%) students, respectively; only 749 (7.8%) of students reported never being involved. At the path analysis explaining the 19.1% of variance of nursing students' involvement, some variables emerged that directly increased the likelihood of being involved in handovers. These were being female (β = 0.115, p < 0.001); having children (β = 0.107, p = 0.011); being a 3rd-year student (β = 0.142, p < 0.001) and being a 2nd-year student as compared to a 1st-year student (β = 0.050, p = 0.036); and having a longer clinical rotation (β = 0.015, p < 0.001) in units with high 'quality of the learning environment' (β = 0.279, p < 0.001). Moreover, students who were supervised by the nurse teacher (β = -0.279, p < 0.001), or by a nurse on a daily basis (β = -0.253, p = 0.004), or by the staff (β = -0.190, p < 0.001) reported being less involved in handovers as compared to those students supervised by a clinical nurse. Variables with indirect effects also emerged (model of student's supervision adopted at the unit level, and number of previous clinical rotations attended by students). Moreover, handover involvement explained 11.5% of students self-reported degree of competences learned during the clinical experience., Conclusions: Limiting students' opportunity to be involved in handover can prevent the development of communication skills and the professional socialization processes. Strategies at different levels are needed to promote handover among undergraduate nursing students., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To explore nursing students' interprofessional educational (IPE) experiences during their most recent clinical rotation and to explore the factors supporting IPE experiences., Design: National cross-sectional study on data collected in 2016., Setting: 95 Bachelor of Nursing Sciences programmes; 27 Italian Universities., Participants: Students who (a) were attending or just completed their clinical rotations lasting at least 2 weeks in the same unit, and (b) willing to participate in the study., Primary and Secondary Outcomes: First to measure the occurrence of IPE experiences in the most recent clinical rotation; the secondary outcome was to discover factors associated with IPE occurrence., Measures: The primary outcome was measured using questions based on a 4-point Likert scale (from 0='never' to 3='always'). Explanatory variables were collected at both individual and regional levels with items included in the same questionnaire., Results: 9607 out of 10 480 students took part in the study. Overall, 666 (6.9%) perceived not having had any IPE experience, while 3248 (33.8%), 3653 (38%) and 2040 (21.3%) reported having experienced IPE opportunities 'only a little', to 'some extent' or 'always', respectively. From the multilevel analysis performed using the generalised linear mixed model, factors promoting the occurrence of IPE experiences were mainly set at (a) the clinical learning environment level (high: learning environment quality, self-directed learning encouragement, learning opportunities, quality of safety and nursing care and quality of tutorial strategies); and (b) the regional level, where significant differences emerged across regions. In contrast, male gender was negatively associated with the perception of having had IPE experiences., Conclusions: A large number of nursing students experienced either 'never' or 'only a little' IPE opportunities, thus suggesting that nursing education tends to remain within the nursing profession. Limiting students' interprofessional exposure during education can prevent future collaborative approaches that have been shown to be essential in providing best patient care. In order to increase IPE exposure, it is necessary to develop strategies designed both at the singular unit and regional levels., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Easy-to-access tools have been demonstrated to improve evidence-based practice (EBP) competences among nursing students. However, students' perception of access to EBP tools (e.g., clinical practice guidelines [CPGs], protocols) is unknown., Aims: To explore: (1) nursing students' opportunity to access EBP tools during their education, and (2) associated factors., Methods: A national cross-sectional study including all Italian nursing programs. Nursing students were deemed eligible according to the following inclusion criteria: Those who (1) were attending or just ended their practical rotation lasting at least 2 weeks at the time of the survey, and (2) expressed through written informed consent their willingness to take part in the study. Participants were asked about their perceived opportunity to access EBP tools during their most recent clinical learning experience (from 0 - not at all to 3 - always). A set of explanatory variables was collected at the individual, nursing program, and regional levels by using a questionnaire., Results: Nine thousand six hundred and seven (91.6%) out of 10,480 nursing students took part in the study. Overall, 4,376 (45.6%) students perceived not at all or only a small opportunity to access EBP tools during their most recent clinical rotation. In the multilevel analysis, factors promoting access were mainly set at the clinical learning environment level (high safety and nursing care quality, high self-directed learning opportunities, high quality of the learning environment, and being supervised by a clinical nurse). In contrast, male gender and lower academic class were associated with a lower perception of accessibility to EBP tools. A consistent variability in the perceived opportunity to access EBP tools emerged across regions., Linking Evidence to Action: Evidence-based decision-making is increasingly expected from nurses. Therefore, nursing faculties should safeguard and continuously improve students' competence regarding EBP, by implementing strategies mainly at the nursing program and regional levels., (© 2018 Sigma Theta Tau International.)

Context: Error reporting is considered one of the most important mediating factors for patient safety (PS). However, reporting errors can be challenging for health care students., Objectives: The aims of the study were: (i) to describe nursing students' opportunity to report errors, near misses or PS issues that emerged during their clinical learning experience; and (ii) to explore associated factors of the process of reporting itself., Methods: A national survey was conducted on 9607 (91.7%) undergraduate nursing students. The endpoint was to have reported PS issues in the last clinical learning experience (from 0 'never' to 3 'always'). Explanatory variables were set individual, nursing programme and regional levels., Results: A total of 4004 (41.7%) nursing students reported PS issues from 'never/rarely' to 'sometimes'. In the multi-level analysis, factors increasing the likelihood of reporting events affecting PS have been mainly at the nursing programme level: specifically, higher learning opportunities (odds ratio [OR] = 3.040; 95% confidence interval [CI], 2.667-3.466), self-directed learning opportunities (OR = 1.491; 95% CI, 1.364-1.630), safety and nursing care quality (OR = 1.411; 95% CI, 1.250-1.594) and quality of tutorial strategies OR = 1.251; 95% CI, 1.113-1.406). By contrast, being supervised by a nurse teacher (OR = 0.523; 95% CI, 0.359-0.761) prevented the disclosure of PS issues compared with being supervised by a clinical nurse. Students attending their nursing programmes in some Italian regions showed a higher likelihood (OR from 1.346 to 2.938) of reporting PS issues compared with those undertaking their education in other regions., Conclusions: Nursing students continue to be reticent to report PS issues. Given that they represent the largest generation of future health care workers, their education regarding PS should be continuously monitored and improved; moreover, strategies aimed at developing a non-blaming culture should be designed and implemented both at the clinical learning setting and regional levels., (© 2018 John Wiley & Sons Ltd and The Association for the Study of Medical Education.)

Background: The Italian Study Group of Hospital Hygiene of the Italian Society of Hygiene, Preventive Medicine and Public Health promoted and conducted a study on teaching hospital hygiene, with particular reference to the prevention and control of healthcare-associated infections, with the aim of developing effective educational material starting from the results collected., Material and Methods: First of all, a survey was carried out, targeting lecturers in hospital hygiene, with the purpose of investigating their perceptions regarding this issue. The available scientific literature was also reviewed in order to identify effective educational/teaching strategies for the prevention of healthcare-associated infections, so that valid training interventions could be subsequently developed. Finally, a trial-training intervention was implemented, and specific audio-visual teaching material was also tested., Results: The overall response rate to the survey was 42%, with good country-wide representativeness. The level of awareness of hospital hygiene issues by students resulted higher among trainee nurses (65%) than among medical students (44%). The teaching staff identified alternative educational methodologies to substitute the classical lecture (e.g.: case discussions) and, in most cases, the alternative solution appeared to be preferable. The teaching of hospital hygiene was better integrated with other disciplines and professional training activities in the degree courses for nurses than in those for doctors; the total number of hours assigned to such teaching was variable. The literature review highlighted that various educational approaches are used. The most common are presentations or lectures, but videos, posters, questionnaires and e-learning strategies are also used. Combining different instruments when designing an educational programme has proven to be an effective strategy. The training activity tested was positively evaluated by the participants; the possibility of multidisciplinary exchange of knowledge was particularly appreciated., Conclusion: Having considered the issue of teaching hospital hygiene from the points of view of the different protagonists involved (educators and students), this enabled us to develop useful training material and a proposal for a shared educational intervention. The subject of hospital hygiene, in particular the one related to the prevention of healthcare-associated infections, is addressed in various courses and with different modalities; it is, therefore, important to standardize course contents and teaching methods, in order to facilitate multidisciplinary debate, especially starting from case studies.

Cell cycle and apoptosis regulator 2 (CCAR2 or DBC1) is a human protein recently emerged as a novel and important player of the DNA damage response (DDR). Indeed, upon genotoxic stress, CCAR2, phosphorylated by the apical DDR kinases ATM and ATR, increases its binding to the NAD+-dependent histone deacetylase SIRT1 and inhibits SIRT1 activity. This event promotes the acetylation and activation of p53, a SIRT1 target, and the subsequent induction of p53 dependent apoptosis. In addition, CCAR2 influences DNA repair pathway choice and promotes the chromatin relaxation necessary for the repair of heterochromatic DNA lesions. However, besides DDR, CCAR2 is involved in several other cellular functions. Indeed, through the interaction with transcription factors, nuclear receptors, epigenetic modifiers and RNA polymerase II, CCAR2 regulates transcription and transcript elongation. Moreover, promoting Rev-erbα protein stability and repressing BMAL1 and CLOCK expression, it was reported to modulate the circadian rhythm. Through SIRT1 inhibition, CCAR2 is also involved in metabolism control and, suppressing RelB and p65 activities in the NFkB pathway, it restricts B cell proliferation and immunoglobulin production. Notably, CCAR2 expression is deregulated in several tumors and, compared to the non-neoplastic counterpart, it may be up- or down-regulated. Since its up-regulation in cancer patients is usually associated with poor prognosis and its depletion reduces cancer cell growth in vitro, CCAR2 was suggested to act as a tumor promoter. However, there is also evidence that CCAR2 functions as a tumor suppressor and therefore its role in cancer formation and progression is still unclear. In this review we discuss CCAR2 functions in the DDR and its multiple biological activities in unstressed cells., (Copyright © 2018 Elsevier B.V. All rights reserved.)

. The Clinical Learning Quality Evaluation Index for nursing students., Introduction: The Italian nursing programs, the need to introduce tools evaluating the quality of the clinical learning as perceived by nursing students. Several tools already exist, however, several limitations suggesting the need to develop a new tool., Aim: A national project aimed at developing and validating a new instrument capable of measuring the clinical learning quality as experience by nursing students., Methods: A validation study design was undertaken from 2015 to 2016. All nursing national programs (n=43) were invited to participate by including all nursing students attending regularly their clinical learning. The tool developed based upon a) literature, b) validated tools already established among other healthcare professionals, and c) consensus expressed by experts and nursing students, was administered to the eligible students., Results: 9606 nursing in 27 universities (62.8%) participated. The psychometric properties of the new instrument ranged from good to excellent. According to the findings, the tool consists in 22 items and five factors: a) quality of the tutorial strategies, b) learning opportunities; c) safety and nursing care quality; d) self-direct learning; e) quality of the learning environment., Conclusions: The tool is already used. Its systematic adoption may support comparison among settings and across different programs; moreover, the tool may also support in accrediting new settings as well as in measuring the effects of strategies aimed at improving the quality of the clinical learning.

Human CCAR2 has recently emerged as having a pivotal role in the DNA damage response, promoting apoptosis and repair of heterochromatic DNA breaks. However, less is known about the function of CCAR2 in tumor formation and cancer progression. Here, we demonstrate, for the first time, that CCAR2 loss inhibits the proliferation of cancer cells, but preserves the growth of normal cells. Investigating the mechanisms responsible for this differential effect, we found that CCAR2 depletion specifically impairs the activation of AKT pathway in cancer cells, but not in normal cells, by reducing AKT phosphorylation on Ser473. This effect is achieved through the transcriptional upregulation of TRB3 gene and accumulation of TRB3 protein, which then binds to and inhibits the phosphorylation and activation of AKT. The defective activation of AKT finally results in reduced GSK3β phosphorylation, prevention of G1/S transition and inhibition of cancer cell growth. These results establish an important role for CCAR2 in cancer cells proliferation and could shed new light on novel therapeutic strategies against cancer, devoid of detrimental side effects.

Unlabelled: . Validation of the Italian Clinical Learning Environment Instrument (SVIAT): study protocol., Introduction: Nursing students obtain most of their university credits in internship environments whose quality can affect their clinical learning. Several tools are available to measure the quality of the clinical learning environment (CLE) as perceived by students: these instruments developed in other countries, were validated in Italian but do not discriminate those CLEs capable (or not) to promote significant clinical learning., Aim: To validate an instrument to measure the capability of the CLE to generate clinical learning; the secondary aim is to describe the learning environments as perceived by nursing students according to individual course site and tutorial models adopted., Methods: The study will be developed in three phases: a) instrument development and pilot phase, b) validation of the psychometric properties of the instrument and c) description of the CLEs as perceived by the students including factors/item confirmed in the validation process. Expected outcomes. A large validation, with more than 8,000 participating students is expected; the construct under lying will be confirmed through exploratory and confirmatory factor analysis and will report high internal consistency; the instrument will report also a high test-retest and inter-rater reliability; in addition, the instrument will demonstrate predictive ability by discriminating those units able (or not) to activate effective learning processes.

Background: Over the last years the ingestion of disk batteries has become frequent in children with serious consequences. The severity of injuries is related to the growing use of new lithium batteries that may cause catastrophic damages when lodged in the oesophagus., Methods: The notes of three consecutive children with lithium batteries lodged in the oesophagus, admitted to our Institute from 2010 to 2014, were reviewed. Clinical presentation, management, and outcome were considered., Results: The first child, a 22-month-old girl, died of a sudden exsanguination due to an aorto-oesophageal fistula. The second case, a 5-year-old boy, had an exploratory thoracotomy to exclude aortic lesion before battery removal, and a spontaneous oesophageal perforation. The third child, a 18-month-old boy, fully recovered after suffering ulcerative oesophageal burns., Conclusion: Lithium battery lodged in the oesophagus is a paediatric emergency requiring a multidisciplinary approach that can be implemented in a tertiary children's hospital., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: ERAS has recently been implemented in pancreatic surgery settings, but there is little evidence regarding the effects as perceived by patients. Given the lack of the knowledge in the field, the aim of this study was to capture the experience of patients undergoing pancreatic surgery who received perioperative care based on the ERAS programme., Methods: We designed a qualitative study undertaken in the pancreatic surgery unit of San Raffaele Hospital in Milan, Italy. Twenty-two consecutive patients were invited to participate in the study and 13 patients were interviewed. Data was collected between March and December 2012 either through face-to-face or semi-structured telephone follow-up from three to six weeks after discharge. Data was analysed using the interpretative phenomenological approach., Results: Patients who underwent surgical pancreatic procedures and treated with ERAS programme reported experiences based on four themes: (1) Feeling prepared to face surgery, (2) Being actively "inside" or "outside" the programme, (3) Healing at home: the best setting, and (4) "Perceiving the ordinary as extraordinary": reaching independence, once at home., Conclusion: According to the findings, uncomplicated pancreatic surgery patients may benefit from the ERAS programme. Preadmission counselling should help patients to assume an active role. Once the patient returns home, the availability of a caregiver should be thoroughly assessed to guarantee the support needed by patients to successfully complete the ERAS(programme. Surgery and nursing staff should carefully monitor patients and suggest whether they continue, interrupt, or individualise the scheduled ERAS interventions in accordance with a patient's clinical condition and preferred personal timing., (Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.)

The aim of the study was to explore the experiences of night nurses. An interpretative phenomenological study was undertaken, and 35 nurses working in Italian medical, surgical and intensive care units were purposely recruited. Data were gathered in 2010 by semi-structured interviews, collecting nurses' narratives, memorable cases and metaphors, aimed at summarising the essence of work as a nurse during the night. The experience of night nursing is based on four interconnected themes: (i) working in a state of alert, (ii) growing by expanding autonomy and responsibility, (iii) assuring sensitive surveillance and (iv) experiencing deep intimacy. Memorable episodes were polarised along (i) expected/unexpected events; (ii) positive/negative epilogues; and (iii) life/death issues. Many of the emergent metaphors described working during the night as being in the middle of a space where an apparent calm scene takes place, but unpredictable factors may suddenly change the order of events and the outcomes, creating chaos. Working during the night alerts nurses, who increase autonomy, expanding their role and assuming more responsibility with respect to that assumed during daily shifts. The nurses' clinical reasoning is based on data they carefully listen to, and on the meaning that nurses give time by time to different noises and silence. While in the past a sense of companionships was reported, a loneliness or a 'neutral' experience concerning the relationships with colleagues seems to prevail during night nursing. Working night shifts is a complex task, and specific training must be assured to students/novices., (© 2015 John Wiley & Sons Ltd.)