Solution Structure and Dynamics of Hf-Al and Hf-Zn Heterobimetallic Adducts Mimicking Relevant Intermediates in Chain Transfer Reactions.

Cationic cyclometalated hafnocenes [CpPrCpCH2CH2CH2Hf][B(C6F5)4] (4Pr) and [CpiBuCpCH2CH(Me)CH2Hf][B(C6F5)4] (4aiBu and 4biBu) were synthesized from the corresponding [(CpPr)2HfMe][B(C6F5)4] (1Pr) and [(CpiBu)2HfMe][B(C6F5)4] (1iBu) complexes via C-H activation. 4aiBu, 4biBu, and 4Pr, mimicking a propagating M-polymeryl species (M = transition metal) with or without a ß-methyl branch on the metalated chains, serve to investigate whether and how the nature of the last inserted olefin molecules changes the structure, stability, and reactivity of the corresponding heterobimetallic complexes, formed in the presence of aluminum- or zinc-alkyl chain transfer agents (CTAs), which are considered relevant intermediates in coordinative chain transfer polymerization (CCTP) and chain shuttling polymerization (CSP) technologies. NMR and DFT data indicate no major structural difference between the resulting heterobridged complexes, all characterized by the presence of multiple α-agostic interactions. On the contrary, thermodynamic and kinetic investigations, concerning the reversible formation and breaking of heterobimetallic adducts, demonstrate that isomer 4aiBu, in which the ß-Me is oriented away from the reactive coordination site on Hf, but not 4biBu, having the ß-Me pointing in the opposite direction, is capable of reacting with CTAs. Quantification of kinetic rate constants highlights that the formation process is rate limiting and that the nature of the last inserted α-olefin unit modulates transalkylation kinetics. The reaction of 4aiBu, 4biBu, and 4Pr with diisobutylaluminum hydride (DiBAlH) allows the interception and characterization of new heterobinuclear and heterotrinuclear species, featuring both hydride and alkyl bridging moieties, which represent structural models of elusive intermediates in CCTP and CSP processes, capturing the instant when an alkyl chain has just transferred from a transition metal to a main group metal, while the two metals remain engaged in a single heterobimetallic intermediate.

Assessing the mental health needs of Yazidi adolescents and young adults in an Iraqi Kurdi IDP Camp: a focus group study.

BACKGROUND: Internally displaced people (IDP) in Iraq are 1.2 million (as March 2023). Protracted refugee status endangers the mental health, especially of minorities who survived persecution and conflict, such as the Yazidis. This study aims to identify the mental health needs of Yazidi adolescents and young adults (AYA) in the IDP camp of Bajed Kandala (Iraqi Kurdistan). METHODS: A focus group discussion (FGD) study was conducted between April and August 2022. The FGDs involved AYAs, as well as the staff of the clinic of the Bajed Kandala camp. An inductive approach was adopted referring to the 'theme' as the unit of content analysis of the text. All FGDs were recorded and transcribed. The analysis was carried out independently by two researchers. The inter-rater agreement was assessed through the Cohen's k. RESULTS: A total of 6 FGDs were conducted. The participants were 34 of whom 21 (61.8%) females with a median age of 18.5 years (IQR 17.0-21.0). A total of 156 themes were found as relevant to the objective of this study. Four main areas and twelve subareas of needs in mental health were identified. The interrater agreement over the main area and subareas was good (κ = 0.78 [0.95CI 0.69-0.88], κ = 0.82 [0.95CI 0.73-0.91], respectively). The four areas had a similar frequency: Activities (28.2%), Individual (27.6%), Social relationships (22.4%) and Places/setting (21.8%). The subareas 'community' and 'internal resources' were labelled as negative 85.7% and 61.9% of the time, respectively. These sub-areas referred to stigma and self-stigma towards mental health. The subarea 'female condition' was always considered as negative, as well as the subareas 'camp' and 'tent' referring to housing as an important social determinant of mental health. CONCLUSIONS: Community stigma and self-stigma are two still important factors preventing the achievement of mental well-being. Alongside these, a gender gap in mental health was identified in the FGDs. These factors should be taken into account in order to guide future mental health interventions in refugee camps.

The use of 12-item General Health Questionnaire (GHQ-12) in Ukrainian refugees: translation and validation study of the Ukrainian version.

Following the Russian-Ukrainian conflict, the well-being of millions of Ukrainians has been jeopardised. This study aims to translate and test the psychometric features of the Ukrainian version of the General Health Questionnaire 12 (GHQ-12). The study included Ukrainian refugees housed in Verona (Italy) between November/2022 and February/2023. The Ukrainian translation was obtained through a 'forward-backward' translation. Questionnaire was completed by 141 refugees (females: 78.7%). Median age was 36 years (IQR 23-43). Individuals with a score suggestive of psychological distress were 97 (68.8%). Cronbach's coefficient was 0.84 (0.95CI 0.80-0.88). According to confirmatory factor analysis, both single- (modelB1) and two-factor (model B2) structures with bimodal scoring method fitted the data satisfactorily. The two factors of model B2 had a 0.88 correlation. Pearson coefficient showed a positive significant correlation between the GHQ-12 and International Trauma Questionnaire scores (ρ = 0.53, 0.95CI 0.40-0.64, p < 0.001). The GHQ-12 Ukrainian translation showed good psychometric features being a reliable and valid instrument to assess Ukrainian refugees' general well-being.

Screening Second Victims for Emotional Distress: Assessment of the Clinimetric Properties of the WITHSTAND-PSY Questionnaire.

INTRODUCTION: Adverse events (AEs) are a leading cause of patient morbidity and mortality, greatly impacting healthcare providers' well-being (second victim (SV) phenomenon). Since it is not accurately captured by existing psychometric instruments, we developed a clinimetric instrument for assessing SVs' emotional distress before and after an AE. METHODS: Content validity and clinical utility of the WITHSTAND-PSY Questionnaire (WS-PSY-Q) were examined using cognitive interviews. Rasch analysis (n = 284) was applied for clinimetric assessment (i.e., construct, concurrent, and clinical validity, internal consistency), considering two crucial psychological facets of the SV phenomenon (1st: emotional impact of the AE, 2nd: current emotional state). RESULTS: The Rasch partial credit model was used. The 1st facet demonstrated overall acceptable clinimetric properties with the subscale anxiety meeting clinimetric threshold values (e.g., all items with ordered thresholds, Loevinger's coefficient h ≥ 0.40; Person Separation Reliability Index (PSI) = 0.7). The 2nd facet showed overall better clinimetric properties for both subscales (e.g., h ≥ 0.40, PSI = 0.82 and 0.79, respectively; receiver operating characteristic area of 0.80 and 0.86, respectively). For both datasets, item fit statistics, except those for item 19, were within the critical range (z-score < ±2.5), and meaningful differential functioning analysis was observed for only 4 (out of 24) items. Local dependency was not observed, except for two item couples in the depression subscales. CONCLUSIONS: The WS-PSY-Q is the first clinimetric tool assessing SVs' emotional distress. It should be regarded as part of the armamentarium used by clinicians to assess in-depth healthcare providers' psychological reactions in the aftermath of an AE to mitigate burnout and allostatic overload.

The COVID-19 vaccination in 4,772 pregnant women in the province of Trento (North-East Italy). Characteristics of vaccinated women.

OBJECTIVES: to investigate vaccine uptake among pregnant women during the 2nd and 3rd trimester of pregnancy. To describe the factors influencing vaccine uptake during pregnancy, comparing sociodemographic and clinical characteristics of pregnant women who were vaccinated during the 2nd or 3rd trimester with those who were not vaccinated, despite having the indication for vaccination. DESIGN: observational study with a cross-sectional approach and prevalence estimation in the population of women who gave birth in the study period, through record linkages between the ministry information flow Birth assistance certificate, the Regional vaccination register and the Italian flow for SARS-CoV-2 infections. SETTING AND PARTICIPANTS: the study included all the 4,772 pregnant women living in Trentino (north-east Italy), who were in the 2nd or 3rd trimester of pregnancy between the 5th May 2021 and the 28th February 2022 and who delivered in Trentino. MAIN OUTCOME MEASURES: vaccine uptake among pregnant women during the 2nd and 3rd trimester of pregnancy. Results: 33.3% of pregnant women got vaccinated with at least one dose of vaccine during the 2nd or 3rd trimester of pregnancy. Independent factors associated with vaccine uptake in the 2nd or 3rd trimester were the mother's citizenship, educational level, occupational status and age. CONCLUSIONS: the proportion of women who received at least one dose of COVID-19 vaccine during pregnancy was low. The results are important to start efficient actions to promote vaccination in pregnant women, particularly in the most vulnerable ones (unemployed, foreigners and with a low educational level), who appear to be less vaccinated frequently.

Comparing swab- and different symptoms-based strategies to ascertain COVID-19 recovery in healthcare workers: a cost-effectiveness analysis.

OBJECTIVE: Given the human and economic cost of the COVID-19 pandemic, protecting healthcare workers (HCW) and ensuring continuity of care is critical. The aim of this study is to evaluate the cost-effectiveness of different strategies to ascertain COVID-19 recovery in HCWs. METHODS: Data were collected from the hospital health surveillance program on HCWs at the University Hospital of Verona between 29/02/2020 and 14/04/2021. The diagnosis of SARS-CoV-2 infection and the assessment of the recovery were made through RT-PCR on oro-nasopharyngeal swab-sample. Recovery time and probability were estimated through Kaplan-Meier estimate. For each recovery assessment strategy costs (laboratory diagnostics and human resources), expressed in local currency (euro-€), and working days saved (WDS-effectiveness) were estimated. A decision-tree was created where each knot was a time point scheduled by the different recovery assessment strategies. A Monte Carlo simulation method was used, and probabilistic sensitivity analysis assessed the effect of input uncertainty. RESULTS: In the study period 916 (9.9%) HCWs tested positive. Recovery time through symptom-based strategy (21 days 0.95 CI 16-24) was significantly lower compared to swab-based one (25 days 0.95 CI 23-28, p < 0.001). The swab-based strategy was dominated by all symptoms-based ones. Symptoms-based with a swab on days 14 and 17 had an ICER of 2 €/WDS and 27 €/WDS compared to the one scheduled on days 10 and 17 and with only one swab on the 17th day. CONCLUSIONS: Scheduling swabs on days 14 and 17 in a symptom-based strategy was the most cost-effective, saving 7.5 more working days than the standard one with swabs on days 10 and 17.

Improving the culture of safety among healthcare workers: Integration of different instruments to gain major insights and drive effective changes.

The Safety Attitude Questionnaire (SAQ) and Manchester Patient Safety Framework (MaPSaF) are known as effective tools to assess patient safety culture and climate and develop targeted strategies. However, they are seldom applied in an integrated way. The aim of this study was to conduct an implementation project through a novel use of both instruments to gain unique insights. The Italian version of MaPSaF and SAQ were administered to 1,759 healthcare workers from three Italian hospitals (response rate: MaPSaF 70.5%, SAQ 61.6%). MaPSaF evaluation proved an overall bureaucratic level of patient safety culture. SAQ scores showed a predominance of neutral scores (75.99%). The dimension perception of management gained the lowest mean score (53.32), while Stress recognition obtained the highest (75.17). Safety climate perception differed significantly among groups: working in a small hospital, in a medical department, and being a physician were associated with the most positive results. The majority (67.1%) of responders to both MaPSaF and SAQ considered the two instruments as providing with different and complementary information. Overall, results showed that an integrated approach in the evaluation of an organisation's safety culture may result useful for an in-depth analysis of the criticalities and the adoption of appropriate improvement strategies.

What We Have Learned from Two Decades of Epidemics and Pandemics: A Systematic Review and Meta-Analysis of the Psychological Burden of Frontline Healthcare Workers.

In light of the current coronavirus disease 2019 (COVID-19) pandemic and potential future infectious disease outbreaks, a comprehensive understanding of the negative effects of epidemics and pandemics on healthcare workers' mental health could inform appropriate support interventions. Thus, we aimed to synthesize and quantify the psychological and psychosomatic symptoms among frontline medical staff. We searched four databases up to March 19, 2020 and additional literature, with daily search alerts set up until October 26, 2020. Studies reporting psychological and/or psychosomatic symptoms of healthcare workers caring for patients with severe acute respiratory syndrome, H1N1, Ebola, Middle East respiratory syndrome, or COVID-19 were eligible for inclusion. Two reviewers independently conducted the search, study selection, quality appraisal, data extraction, and synthesis and involved a third reviewer in case of disagreement. We used random effects modeling to estimate the overall prevalence rates of psychological/psychosomatic symptoms and the I2 statistic. We included 86 studies, reporting data from 75,991 participants. Frontline staff showed a wide range of symptoms, including concern about transmitting the virus to the family (60.39%, 95% CI 42.53-76.96), perceived stress (56.77%, 95% CI 34.21-77.95), concerns about own health (45.97%, 95% CI 31.08-61.23), sleeping difficulties (39.88%, 95% CI 27.70-52.72), burnout (31.81%, 95% CI 13.32-53.89), symptoms of depression (25.72%, 95% CI 18.34-33.86), symptoms of anxiety (25.36%, 95% CI 17.90-33.64), symptoms of posttraumatic stress disorder (24.51%, 95% CI 18.16-31.46), mental health issues (23.11%, 95% CI 15.98-31.10), and symptoms of somatization (14.68%, 95% CI 10.67-19.18). We found consistent evidence for the pervasive and profound impact of large-scale outbreaks on the mental health of frontline healthcare workers. As the CO-VID-19 crisis continues to unfold, guaranteeing easy access to support structures for the entire healthcare workforce is vitally important.

Genome-wide CRISPR screen for PARKIN regulators reveals transcriptional repression as a determinant of mitophagy.

PARKIN, an E3 ligase mutated in familial Parkinson's disease, promotes mitophagy by ubiquitinating mitochondrial proteins for efficient engagement of the autophagy machinery. Specifically, PARKIN-synthesized ubiquitin chains represent targets for the PINK1 kinase generating phosphoS65-ubiquitin (pUb), which constitutes the mitophagy signal. Physiological regulation of PARKIN abundance, however, and the impact on pUb accumulation are poorly understood. Using cells designed to discover physiological regulators of PARKIN abundance, we performed a pooled genome-wide CRISPR/Cas9 knockout screen. Testing identified genes individually resulted in a list of 53 positive and negative regulators. A transcriptional repressor network including THAP11 was identified and negatively regulates endogenous PARKIN abundance. RNAseq analysis revealed the PARKIN-encoding locus as a prime THAP11 target, and THAP11 CRISPR knockout in multiple cell types enhanced pUb accumulation. Thus, our work demonstrates the critical role of PARKIN abundance, identifies regulating genes, and reveals a link between transcriptional repression and mitophagy, which is also apparent in human induced pluripotent stem cell-derived neurons, a disease-relevant cell type.

Binaural Beats Reduce Postoperative Morphine Consumption in Older adults After Total Knee Replacement Surgery.

CONTEXT: A reduction in the use of opioids by older adult patients could reduce unpleasant side effects for them. During general anesthesia, binaural beat (BB) listening has been found to reduce intraoperative fentanyl consumption as well as postoperative pain scores and discharge time. Auditory BBs are a perceptual phenomenon occurring when tones of 2 slightly different frequencies are presented simultaneously and separately to each ear. OBJECTIVE: The study intended to evaluate the ability of BBs, as a nonpharmacological premedication, to reduce postoperative morphine consumption in older adults undergoing total knee replacement surgery and to modify the levels of anxiety and feelings of pain that patients experience. DESIGN: The research team designed a prospective, single-center, randomized controlled study. SETTING: The study was conducted in the Orthopedic Department of the Santa Maria Maddalena Hospital (Volterra [Pisa], Italy). PARTICIPANTS: Forty older adults at the hospital who were undergoing total knee joint replacement with spinal anesthesia participated in the study. INTERVENTION: The study included 2 groups (n = 20 each), one receiving BBs stimulation with frequencies of 256 Hz in one ear and 260 Hz in the opposite ear producing a BB of 4 Hz (intervention group), and the other receiving acoustical stimulation at 256 Hz in both ears (control group). BBs, or acoustical stimulation, were administered before the surgical procedure. Both acoustical stimuli, generated with the Gnaural program, were delivered through stereo headphones connected to a laptop in the preoperative holding area. OUTCOME MEASURES: The study measured postoperative, cumulative, self-administered morphine consumption, in mg, through a patient-controlled analgesia device. Feelings of anxiety were also assessed using the State-Trait Anxiety Inventory, and feelings of pain were measured every 8 h during the first postoperative day using a numerical rating scale. RESULTS: Patients who received the intervention, consumed almost half of the dosage of morphine during the first postoperative day when compared with the control group's consumption, 5.75 mg ± 5.25 vs 11.85 mg ± 7.71, respectively. The consumption did not correlate to anxiety measures. Regarding pain perception, no differences between the groups were captured. CONCLUSIONS: BB stimulation before surgery can be successfully used as a nonpharmacological treatment to reduce morphine consumption in older adults who undergo knee replacement. The use of a noninvasive, safe, and inexpensive BB intervention can result in a positive effect on patients' postoperative recovery.

TMEM41B is a novel regulator of autophagy and lipid mobilization.

Autophagy maintains cellular homeostasis by targeting damaged organelles, pathogens, or misfolded protein aggregates for lysosomal degradation. The autophagic process is initiated by the formation of autophagosomes, which can selectively enclose cargo via autophagy cargo receptors. A machinery of well-characterized autophagy-related proteins orchestrates the biogenesis of autophagosomes; however, the origin of the required membranes is incompletely understood. Here, we have applied sensitized pooled CRISPR screens and identify the uncharacterized transmembrane protein TMEM41B as a novel regulator of autophagy. In the absence of TMEM41B, autophagosome biogenesis is stalled, LC3 accumulates at WIPI2- and DFCP1-positive isolation membranes, and lysosomal flux of autophagy cargo receptors and intracellular bacteria is impaired. In addition to defective autophagy, TMEM41B knockout cells display significantly enlarged lipid droplets and reduced mobilization and ß-oxidation of fatty acids. Immunostaining and interaction proteomics data suggest that TMEM41B localizes to the endoplasmic reticulum (ER). Taken together, we propose that TMEM41B is a novel ER-localized regulator of autophagosome biogenesis and lipid mobilization.

Predicting Patients' Readmission: Do Clinicians Outperform a Statistical Model? An Exploratory Study on Clinical Risk Judgment in Mental Health.

This study explores whether clinicians or a statistical model can better identify patients at risk of early readmission and investigates variables potentially associated with clinicians' risk judgment. We focus on a total of 142 patients discharged from acute psychiatric wards in the Verona Mental Health Department (Italy). Psychiatrists assessed patients' risk of readmission at 30 and 90 days postdischarge, predicted their postdischarge compliance, and assessed their Global Assessment of Functioning (GAF) score at admission and discharge. Clinicians' judgment outperformed the statistical model, with the difference reaching statistical significance for 30-day readmission. Clinicians' readmission risk judgment, both for 30 and 90 days, was found to be statistically associated with predicted compliance with community treatment and GAF score at discharge. Clinicians' superior performance might be explained by their risk judgment depending on nonmeasurable factors, such as experience and intuition. Patients with a poorer GAF score at discharge and poor assumed compliance were predicted to have a higher risk of readmission.

Knowledge and use of e-cigarettes among nursing students: results from a cross-sectional survey in north-eastern Italy.

BACKGROUND: Data on electronic cigarette (e-cigarette) use among health professional students, who can play a central role in promoting healthy habits and smoking cessation, are sparse. Moreover, the association between e-cigarettes and smoking habits is still debated. The present study aimed to investigate the diffusion of e-cigarette use among nursing students in north-eastern Italy and explore its association with tobacco smoking. METHODS: In 2015, a questionnaire focused on e-cigarette use and tobacco smoking habits was anonymously administered to 2020 students attending nursing courses held by Verona University in 5 different centres. Of these students, 1463 (72.4%) answered the questionnaire. The influence of e-cigarette ever use on both tobacco smoking initiation in all subjects and smoking cessation among ever smokers was investigated by multivariable logistic models. RESULTS: Most responders were female (77.1%), and the mean (SD) age was 23.2 (4.2) years. Nearly all students (94.7%) had heard about e-cigarettes. Approximately one-third (30.3, 95% CI 27.9-32.7%) had ever used e-cigarettes, but only 2.1% (1.5-3.0%) had used e-cigarettes in the last month. Very few (2.1%) of those responders who had never used e-cigarettes were willing to try them. Prevalence values were much higher for tobacco smoking: 40.9% of responders reported being current tobacco smokers, and 10.1% reported being past smokers. Ever use and current use of e-cigarettes were reported by 57.2 and 4.4% of current tobacco smokers and by 12.0 and 0.6% of never or past smokers, respectively (p < 0.001). In multivariable analysis, students who ever used e-cigarettes had 13 times greater odds of being an ever tobacco smoker than never users, whereas they had three times lower odds of being a former smoker. Only 26 students were currently using both electronic and tobacco cigarettes, and most declared that they used e-cigarettes to stop or reduce tobacco smoking. Of note, only three students reported that they had completely stopped smoking thanks to e-cigarette use. CONCLUSION: Use of e-cigarettes seemed to be rather rare among Italian nursing students and was mainly restricted to current smokers. E-cigarette use was not associated with smoking cessation in nursing students.

Reducing interruptions during medication preparation and administration.

PURPOSE: According to literature, interruptions during drug administration lead to a significant proportion of medication errors. Evidence on the effectiveness of interventions to reduce interruption is still limited. The purpose of this paper is to explore main reasons for interruptions during drug administration rounds in a geriatric ward of an Italian secondary hospital and test the effectiveness of a combined intervention. DESIGN/METHODOLOGY/APPROACH: This is a pre and post-intervention observational study based on direct observation. All nurse staff (24) participated to the study that lead to observe a total of 44 drug dispensing rounds with 945 drugs administered to 491 patients in T0 and 994 drugs to 506 patients in T1. FINDINGS: A significant reduction of raw number of interruptions (mean per round from 17.31 in T0 to 9.09 in T1, p<0.01), interruptions/patient rate (from 0.78 in T0 to 0.40 in T1, p<0.01) and interruptions/drugs rate (from 0.44 in T0 to 0.22 in T1, p<0.01) were observed. Needs for further improvements were elicited (e.g. a greater involvement of support staff). PRACTICAL IMPLICATIONS: Nurse staff should be adequately trained on the risks related to interruptions during drug administration since routine activity is at high risk of distractions due to its repetitive and skill-based nature. ORIGINALITY/VALUE: A strong involvement of both MB and leadership, together with the frontline staff, helped to raise staff motivation and guide a bottom-up approach, able to identify tailored interventions and serve concurrently as training instrument tool.

Clinical Assessment of Risk Management: an INtegrated Approach (CARMINA).

Purpose - The European Union recommendations for patient safety calls for shared clinical risk management (CRM) safety standards able to guide organizations in CRM implementation. The purpose of this paper is to develop a self-evaluation tool to measure healthcare organization performance on CRM and guide improvements over time. Design/methodology/approach - A multi-step approach was implemented including: a systematic literature review; consensus meetings with an expert panel from eight Italian leader organizations to get to an agreement on the first version; field testing to test instrument feasibility and flexibility; Delphi strategy with a second expert panel for content validation and balanced scoring system development. Findings - The self-assessment tool - Clinical Assessment of Risk Management: an INtegrated Approach includes seven areas (governance, communication, knowledge and skills, safe environment, care processes, adverse event management, learning from experience) and 52 standards. Each standard is evaluated according to four performance levels: minimum; monitoring; outcomes; and improvement actions, which resulted in a feasible, flexible and valid instrument to be used throughout different organizations. Practical implications - This tool allows practitioners to assess their CRM activities compared to minimum levels, monitor performance, benchmarking with other institutions and spreading results to different stakeholders. Originality/value - The multi-step approach allowed us to identify core minimum CRM levels in a field where no consensus has been reached. Most standards may be easily adopted in other countries.

Long noncoding RNA HOTTIP/HOXA13 expression is associated with disease progression and predicts outcome in hepatocellular carcinoma patients.

UNLABELLED: Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related death. Despite the advances in diagnosis and management of HCC, the biology of this tumor remains poorly understood. Recent evidence highlighted long noncoding RNAs (lncRNAs) as crucial determinants of HCC development. In this study we report the lncRNA HOXA transcript at the distal tip (HOTTIP) as significantly up-regulated in HCC specimens. The HOTTIP gene is located in physical contiguity with HOXA13 and directly controls the HOXA locus gene expression by way of interaction with the WDR5/MLL complex. HOX genes encode transcription factors regulating embryonic development and cell fate. We previously described HOX genes deregulation to be involved in hepatocarcinogenesis. Indeed, we observed the marked up-regulation of HOXA13 in HCC. Here, by correlating clinicopathological and expression data, we demonstrate that the levels of HOTTIP and HOXA13 are associated with HCC patients' clinical progression and predict disease outcome. In contrast to the majority of similar studies, our data were obtained from snap-frozen needle HCC biopsies (n=52) matched with their nonneoplastic counterparts collected from patients who had not yet received any HCC-tailored therapeutic treatments at the time of biopsy. In addition, taking advantage of gain and loss of function experiments in liver cancer-derived cell lines (HuH-6 and HuH-7), we uncover a novel bidirectional regulatory loop between HOTTIP/HOXA13. CONCLUSION: Our study highlights the key role of HOTTIP and HOXA13 in HCC development by associating their expression with metastasis and survival in HCC patients, provides novel insights on the function of lncRNA-driven hepatocarcinogenesis, and paves the way for further investigation about the possible role of HOTTIP as a predictive biomarker of HCC.

Growth cone MKK7 mRNA targeting regulates MAP1b-dependent microtubule bundling to control neurite elongation.

Local mRNA translation in neurons has been mostly studied during axon guidance and synapse formation but not during initial neurite outgrowth. We performed a genome-wide screen for neurite-enriched mRNAs and identified an mRNA that encodes mitogen-activated protein kinase kinase 7 (MKK7), a MAP kinase kinase (MAPKK) for Jun kinase (JNK). We show that MKK7 mRNA localizes to the growth cone where it has the potential to be translated. MKK7 is then specifically phosphorylated in the neurite shaft, where it is part of a MAP kinase signaling module consisting of dual leucine zipper kinase (DLK), MKK7, and JNK1. This triggers Map1b phosphorylation to regulate microtubule bundling leading to neurite elongation. We propose a model in which MKK7 mRNA localization and translation in the growth cone allows for a mechanism to position JNK signaling in the neurite shaft and to specifically link it to regulation of microtubule bundling. At the same time, this uncouples activated JNK from its functions relevant to nuclear translocation and transcriptional activation.

Quality of doctor-patient communication through the eyes of the patient: variation according to the patient's educational level.

Good doctor-patient communication may lead to better compliance, higher patient satisfaction, and finally, better health. Although the social variance in how physicians and patients communicate is clearly demonstrated, little is known about what patients with different educational attainments actually prefer in doctor-patient communication. In this study we describe patients' perspective in doctor-patient communication according to their educational level, and to what extent these perspectives lean towards the expert opinion on doctor-patient communication. In a multi-center study (Belgium, The Netherlands, UK and Italy), focus group discussions were organised using videotaped medical consultations. A mixed methods approach was used to analyse the data. Firstly, a difference in perspective in communication style was found between the lower educated participants versus the middle and higher educated participants. Secondly, lower educated participants referred positively most to aspects related to the affective/emotional area of the medical consultation, followed by the task-oriented/problem-focused area. Middle and higher educated participants positively referred most to the task-oriented/problem-focused area. The competency of the physician was an important category of communication for all participants, independent of social background. The results indicate that the preferences of lower educated participants lean more towards the expert opinion in doctor-patient communication than the middle and higher educated participants. Patients' educational level seems to influence their perspective on communication style and should be taken into account by physicians. Further quantitative research is needed to confirm these results.

What do people appreciate in physicians' communication? An international study with focus groups using videotaped medical consultations.

BACKGROUND: The literature shows that the quality of communication is usually determined from a professional perspective. Patients or lay people are seldom involved in the development of quality indicators or communication. OBJECTIVE: To give voice to the lay people perspective on what constitutes 'good communication' by evoking their reactions to variations in physician communication. DESIGN: Lay people from four different countries watched the same videotaped standardized medical encounters and discussed their preferences in gender-specific focus groups who were balanced in age groups. SETTING AND PARTICIPANTS: Two hundred and fifty-nine lay people (64 NL, 72 IT, 75 UK and 48 BE) distributed over 35 focus groups of 6-8 persons each. MAIN VARIABLES STUDIED: Comments on doctors' behaviours were classified by the GULiVer framework in terms of contents and preferences. RESULTS: Participants prevalently discussed 'task-oriented expressions' (39%: competency, self-confident, providing solutions), 'affective oriented/emotional expressions' (25%: empathy, listening, reassuring) and 'process-oriented expressions' (23%: flexibility, summarizing, verifying). 'Showing an affective attitude' was most appreciated (positive percentage within category: 93%, particularly facilitations and inviting attitude), followed by 'providing solution' (85%). Among disfavoured behaviour, repetitions (88%), 'writing and reading' (54%) and asking permission (42%) were found. CONCLUSIONS: Although an affective attitude is appreciated by nearly everybody, people may vary widely in their communication needs and preferences: what is 'good communication' for one person may be disliked or even a source of irritation for another. A physician should be flexible and capable of adapting the consultation to the different needs of different patients. This challenges the idea of general communication guidelines.

Docosahexaenoic Acid Levels in Blood and Metabolic Syndrome in Obese Children: Is There a Link?

Prevalence of metabolic syndrome is increasing in the pediatric population. Considering the different existing criteria to define metabolic syndrome, the use of the International Diabetes Federation (IDF) criteria has been suggested in children. Docosahexaenoic acid (DHA) has been associated with beneficial effects on health. The evidence about the relationship of DHA status in blood and components of the metabolic syndrome is unclear. This review discusses the possible association between DHA content in plasma and erythrocytes and components of the metabolic syndrome included in the IDF criteria (obesity, alteration of glucose metabolism, blood lipid profile, and blood pressure) and non-alcoholic fatty liver disease in obese children. The current evidence is inconsistent and no definitive conclusion can be drawn in the pediatric population. Well-designed longitudinal and powered trials need to clarify the possible association between blood DHA status and metabolic syndrome.