How snoRNAs can contribute to cancer at multiple levels.

snoRNAs are a class of non-coding RNAs known to guide site specifically RNA modifications such as 2'-O-methylation and pseudouridylation. Recent results regarding snoRNA alterations in cancer has been made available and suggest their potential evaluation as diagnostic and prognostic biomarkers. A large part of these data, however, was not consistently confirmed and failed to provide mechanistic insights on the contribution of altered snoRNA expression to the neoplastic process. Here, we aim to critically review the available literature on snoRNA in cancer focusing on the studies elucidating the functional consequences of their deregulation. Beyond the canonical guide function in RNA processing and modification we also considered additional roles in which snoRNA, in various forms and through different modalities, are involved and that have been recently reported.

Decoding Ribosome Heterogeneity: A New Horizon in Cancer Therapy.

The traditional perception of ribosomes as uniform molecular machines has been revolutionized by recent discoveries, revealing a complex landscape of ribosomal heterogeneity. Opposing the conventional belief in interchangeable ribosomal entities, emerging studies underscore the existence of specialized ribosomes, each possessing unique compositions and functions. Factors such as cellular and tissue specificity, developmental and physiological states, and external stimuli, including circadian rhythms, significantly influence ribosome compositions. For instance, muscle cells and neurons are characterized by distinct ribosomal protein sets and dynamic behaviors, respectively. Furthermore, alternative forms of ribosomal RNA (rRNAs) and their post-transcriptional modifications add another dimension to this heterogeneity. These variations, orchestrated by spatial, temporal, and conditional factors, enable the manifestation of a broad spectrum of specialized ribosomes, each tailored for potentially distinct functions. Such specialization not only impacts mRNA translation and gene expression but also holds significant implications for broader biological contexts, notably in the realm of cancer research. As the understanding of ribosomal diversity deepens, it also paves the way for exploring novel avenues in cellular function and offers a fresh perspective on the molecular intricacies of translation.

The therapeutic relationship in community mental health services: a systematic review of the literature.

PURPOSE: This systematic review aimed to investigate the therapeutic relationship (TR) between mental health professionals (MHPs) and their patients in community mental health services (CMHS). METHODS: PubMed (Medline), PsycINFO, CINAHL, CENTRAL, and Web of Science were searched for studies that assessed TR in CMHS using quantitative measures developed specifically for this setting (i.e., Helping Alliance Scale [HAS] and the Scale to Assess the Therapeutic Relationship [STAR]). Studies were included if they considered adult patients with a psychiatric disorder and/or any MHP working in CMHS. Meta-analysis and narrative synthesis assessed the association between patients' and MHPs' ratings and identified predictors of TR. RESULTS: Of 1934 studies, 15 were included in the review, including 3004 patients. A total of 1127 patients and 963 MHPs were considered in the meta-analysis. The heterogeneity of the studies was high, and there was no significant difference between the patients' and MHPs' TR ratings in the random-effects model (standardized mean difference [SMD]: - 0.39 [95% CI: - 1.03; 0.24]). In the multivariable meta-regression, only duration of illness was significantly associated with TR ratings (unstandardized regression coefficient [B]: 0.388 [95% CI: 0.217; 0.558]). A recovery-oriented service, shared decision-making, and the recognition of patient needs contributed to more positive TR ratings. CONCLUSION: Patients and MHPs converged in their TR ratings, although patients gave lower ratings. Routine assessment of TR in CMHS can inform reflective practice and service development, as TR can be assessed easily and early in the treatment process. Future research should focus on developing and testing interventions to improve TR in CMHS.

ADHD Follow-Up in Adulthood among Subjects Treated for the Disorder in a Child and Adolescent Mental Health Service from 1995 to 2015.

Background and Objectives: ADHD is a neurodevelopmental disorder characterized by inattention and hyperactivity/impulsivity and can persist in adulthood. The aim of this study is to deepen knowledge about adult ADHD follow-up. Materials and Methods: This observational study consists of one retrospective part aimed at collecting records of children and adolescents treated for ADHD in the Children and Adolescent Mental Health Service (CAMHS) from 1995 to 2015 and, successively, at identifying their adult follow-up in Adult Mental Health Service (AMHS); the second part consists of ADHD scale administration, Diagnostic Interview for ADHD in Adults (DIVA 2-0) and Adult Self Rating Scale (ASRSv1.1), for the subjects currently being treated at AMHS who agreed to participate in the study. Results: We observed that among the 55 patients treated at CAMHS between 1995 and 2015 for ADHD and subsequently at the AMHS, none presented a diagnosis of ADHD; instead, they were treated for Intellectual Dysfunction (33%), Borderline Personality Disorder (15%) and Anxiety Disorders (9%), and two individuals were also diagnosed with comorbid substance/alcohol abuse (4%). Of the 55 patients, only 25 (45%) were treated at AMHS during the study period. Though we asked for their informed consent to administer the questionnaires, we were able to test only seven patients. The ASRS-V1.1 score showed that 43% of patients reported symptoms of ADHD persistence in adulthood. For DIVA 2.0, 57% of individuals reported scores indicating the persistence of the ADHD inattention component, and 43% the persistence of both ADHD dimensions. Conclusions: ADHD cannot be considered a disorder confined to childhood/adolescence but instead is a chronic and complex condition that can persist into adulthood. The very small size of our final sample may account for both the high ADHD dropout rate over the long follow-up period and the difficult transition from child to adult health care in ADHD treatment. Our investigation suggests the need for specific training in the diagnosis and treatment of adult ADHD and the implementation of transition protocols between minor and adult services to improve long-term treatments.

N-Glycan on the Non-Consensus N-X-C Glycosylation Site Impacts Activity, Stability, and Localization of the Sda Synthase B4GALNT2.

The Sda carbohydrate epitope and its biosynthetic B4GALNT2 enzyme are expressed in the healthy colon and down-regulated to variable extents in colon cancer. The human B4GALNT2 gene drives the expression of a long and a short protein isoform (LF-B4GALNT2 and SF-B4GALNT2) sharing identical transmembrane and luminal domains. Both isoforms are trans-Golgi proteins and the LF-B4GALNT2 also localizes to post-Golgi vesicles thanks to its extended cytoplasmic tail. Control mechanisms underpinning Sda and B4GALNT2 expression in the gastrointestinal tract are complex and not fully understood. This study reveals the existence of two unusual N-glycosylation sites in B4GALNT2 luminal domain. The first atypical N-X-C site is evolutionarily conserved and occupied by a complex-type N-glycan. We explored the influence of this N-glycan using site-directed mutagenesis and showed that each mutant had a slightly decreased expression level, impaired stability, and reduced enzyme activity. Furthermore, we observed that the mutant SF-B4GALNT2 was partially mislocalized in the endoplasmic reticulum, whereas the mutant LF-B4GALNT2 was still localized in the Golgi and post-Golgi vesicles. Lastly, we showed that the formation of homodimers was drastically impaired in the two mutated isoforms. An AlphaFold2 model of the LF-B4GALNT2 dimer with an N-glycan on each monomer corroborated these findings and suggested that N-glycosylation of each B4GALNT2 isoform controlled their biological activity.

Transjugular intrahepatic Porto-systemic shunt positively influences the composition and metabolic functions of the gut microbiota in cirrhotic patients.

BACKGROUND & AIMS: Cirrhosis and its complications may affect gut microbiota (GM) composition. Transjugular intrahepatic portosystemic shunt (TIPS) represents the most effective treatment for portal hypertension (PH). We aimed to evaluate whether TIPS placement modifies GM composition and metabolic function. METHODS: A compositional and functional GM analysis was prospectively performed in 13 cirrhotic patients receiving TIPS. Patients receiving systemic or non-absorbable antibiotics for any indications were excluded. Fecal samples were collected before and three months after TIPS. GM was analyzed by 16S ribosomal RNA sequencing. Small- and medium-chain fatty acids (SCFAs and MCFAs, respectively) were measured by gas chromatography/mass spectrometry. RESULTS: TIPS placement resulted in a mean 48% reduction in portal-caval pressure gradient. No recurrence of PH related complications was observed. After TIPS, increased levels of Flavonifractor spp. (p = 0.049), and decreased levels of Clostridiaceae (p = 0.024), these latter linked to abdominal infections in cirrhotic patients, were observed. No differences were found in the SCFAs signature while analysis of MCFA profiles showed a decreased abundance of pro-inflammatory isohexanoic (p<0.01), 2-ethylhexanoic (p<0.01) and octanoic acids (p<0.01) after TIPS. CONCLUSION: Correction of PH following TIPS results in modifications of GM composition which could be potentially beneficial and reduces the levels of fecal pro-inflammatory MCFAs.

The ParlaMint corpora of parliamentary proceedings.

This paper presents the ParlaMint corpora containing transcriptions of the sessions of the 17 European national parliaments with half a billion words. The corpora are uniformly encoded, contain rich meta-data about 11 thousand speakers, and are linguistically annotated following the Universal Dependencies formalism and with named entities. Samples of the corpora and conversion scripts are available from the project's GitHub repository, and the complete corpora are openly available via the CLARIN.SI repository for download, as well as through the NoSketch Engine and KonText concordancers and the Parlameter interface for on-line exploration and analysis.

ATM Regulates Differentiation of Myofibroblastic Cancer-Associated Fibroblasts and Can Be Targeted to Overcome Immunotherapy Resistance.

Myofibroblastic cancer-associated fibroblast (myoCAF)-rich tumors generally contain few T cells and respond poorly to immune-checkpoint blockade. Although myoCAFs are associated with poor outcome in most solid tumors, the molecular mechanisms regulating myoCAF accumulation remain unclear, limiting the potential for therapeutic intervention. Here, we identify ataxia-telangiectasia mutated (ATM) as a central regulator of the myoCAF phenotype. Differentiating myofibroblasts in vitro and myoCAFs cultured ex vivo display activated ATM signaling, and targeting ATM genetically or pharmacologically could suppress and reverse differentiation. ATM activation was regulated by the reactive oxygen species-producing enzyme NOX4, both through DNA damage and increased oxidative stress. Targeting fibroblast ATM in vivo suppressed myoCAF-rich tumor growth, promoted intratumoral CD8 T-cell infiltration, and potentiated the response to anti-PD-1 blockade and antitumor vaccination. This work identifies a novel pathway regulating myoCAF differentiation and provides a rationale for using ATM inhibitors to overcome CAF-mediated immunotherapy resistance. SIGNIFICANCE: ATM signaling supports the differentiation of myoCAFs to suppress T-cell infiltration and antitumor immunity, supporting the potential clinical use of ATM inhibitors in combination with checkpoint inhibition in myoCAF-rich, immune-cold tumors.

Higher readability of institutional websites drives the correct fruition of the abortion pathway: A cross-sectional study.

BACKGROUND: In Italy, abortion services are public: therefore, health Institutions should provide clear and easily readable web-based information. We aimed to 1) assess variation in abortion services utilisation; 2) analyse the readability of institutional websites informing on induced abortion; 3) explore whether easier-to-read institutional websites influenced the correct fruition of abortion services. METHODS: We identified from the 2021 administrative databases of Tuscany all women having an abortion, and-among them-women having an abortion with the certification provided by family counselling centres, following the pathway established by law. We assessed variation in total and certified abortion rates by computing the Systematic Component of Variation. We analysed the readability of the Tuscan health authorities' websites using the readability assessment tool READ-IT. We explored how institutional website readability influenced the odds of having certified abortions by running multilevel logistic models, considering health authorities as the highest-level variables. RESULTS: We observed high variation in the correct utilization of the abortion pathway in terms of certified abortion rates. The READ-IT scores showed that the most readable text was from the Florence Teaching Hospital website. Multilevel models revealed that higher READ-IT scores, corresponding to more difficult texts, resulted in lower odds of certified abortions. CONCLUSIONS: Large variation in the proper fruition of abortion pathways occurs in Tuscany, and such variation may depend on readability of institutional websites informing on induced abortion. Therefore, health Institutions should monitor and improve the readability of their websites to ensure proper and more equitable access to abortion.

Human dyskerin binds to cytoplasmic H/ACA-box-containing transcripts affecting nuclear hormone receptor dependence.

BACKGROUND: Dyskerin is a nuclear protein involved in H/ACA box snoRNA-guided uridine modification of RNA. In humans, its defective function is associated with cancer development and induces specific post-transcriptional alterations of gene expression. In this study, we seek to unbiasedly identify mRNAs regulated by dyskerin in human breast cancer-derived cells. RESULTS: We find that dyskerin depletion affects the expression and the association with polysomes of selected mRNA isoforms characterized by the retention of H/ACA box snoRNA-containing introns. These snoRNA retaining transcripts (snoRTs) are bound by dyskerin in the cytoplasm in the form of shorter 3' snoRT fragments. We then characterize the whole cytoplasmic dyskerin RNA interactome and find both H/ACA box snoRTs and protein-coding transcripts which may be targeted by the snoRTs' guide properties. Since a fraction of these protein-coding transcripts is involved in the nuclear hormone receptor binding, we test to see if this specific activity is affected by dyskerin. Obtained results indicate that dyskerin dysregulation may alter the dependence on nuclear hormone receptor ligands in breast cancer cells. These results are paralleled by consistent observations on the outcome of primary breast cancer patients stratified according to their tumor hormonal status. Accordingly, experiments in nude mice show that the reduction of dyskerin levels in estrogen-dependent cells favors xenograft development in the absence of estrogen supplementation. CONCLUSIONS: Our work suggests a cytoplasmic function for dyskerin which could affect mRNA post-transcriptional networks relevant for nuclear hormone receptor functions.

Linguistically-Based Comparison of Different Approaches to Building Corpora for Text Simplification: A Case Study on Italian.

In this paper, we present an overview of existing parallel corpora for Automatic Text Simplification (ATS) in different languages focusing on the approach adopted for their construction. We make the main distinction between manual and (semi)-automatic approaches in order to investigate in which respect complex and simple texts vary and whether and how the observed modifications may depend on the underlying approach. To this end, we perform a two-level comparison on Italian corpora, since this is the only language, with the exception of English, for which there are large parallel resources derived through the two approaches considered. The first level of comparison accounts for the main types of sentence transformations occurring in the simplification process, the second one examines the results of a linguistic profiling analysis based on Natural Language Processing techniques and carried out on the original and the simple version of the same texts. For both levels of analysis, we chose to focus our discussion mostly on sentence transformations and linguistic characteristics that pertain to the morpho-syntactic and syntactic structure of the sentence.

Primer extension coupled with fragment analysis for rapid and quantitative evaluation of 5.8S rRNA isoforms.

The ribosomal RNA 5.8S is one of the four rRNAs that constitute ribosomes. In human cells, like in all eukaryotes, it derives from the extensive processing of a long precursor containing the sequence of 18S, 5.8S and 28S rRNAs. It has been confirmed also in human cells the presence of three isoforms of 5.8S rRNA: one more abundant called 5.8S short, one called 5.8S long bearing 5 extra-nucleotides at its 5' end and one 10 nucleotide shorter called 5.8S cropped. So far, little is known about 5.8S long specific role in cell biology and its function in human pathology. The lack of studies on the three 5.8S isoforms could be due to the techniques usually applied to study ribosome biogenesis, such as Northern blot with radioactively labelled probes, that require strict protective measures, and abundant and high-quality samples. To overcome this issue, we optimized a method that combines primer extension with a fluorescently labeled reverse primer designed on the 3' of 5.8S rRNA sequence and fragment analysis. The resulting electropherogram shows the peaks corresponding to the three isoforms of 5.8S rRNA. The estimation of the area underneath the peaks allows to directly quantify the isoforms and to express their relative abundance. The relative abundance of 5.8S long and 5.8S short remains constant using scalar dilution of RNA and in samples subjected to partial degradation. 5.8S cropped abundance varies significantly in lower concentrate RNA samples. This method allows to analyze rapidly and safely the abundance of 5.8S rRNA isoforms in samples that have been so far considered not suitable such as poorly concentrated samples, RNA derived from frozen tissue or unique samples.

Analysis of the proximal promoter of the human colon-specific B4GALNT2 (Sda synthase) gene: B4GALNT2 is transcriptionally regulated by ETS1.

BACKGROUND: The Sda antigen and corresponding biosynthetic enzyme B4GALNT2 are primarily expressed in normal colonic mucosa and are down-regulated to a variable degree in colon cancer tissues. Although their expression profile is well studied, little is known about the underlying regulatory mechanisms. METHODS: To clarify the molecular basis of Sda expression in the human gastrointestinal tract, we investigated the transcriptional regulation of the human B4GALNT2 gene. The proximal promoter region was delineated using luciferase assays and essential trans-acting factors were identified through transient overexpression and silencing of several transcription factors. RESULTS: A short cis-regulatory region restricted to the -72 to +12 area upstream of the B4GALNT2 short-type transcript variant contained the essential promoter activity that drives the expression of the human B4GALNT2 regardless of the cell type. We further showed that B4GALNT2 transcriptional activation mostly requires ETS1 and to a lesser extent SP1. CONCLUSIONS: Results presented herein are expected to provide clues to better understand B4GALNT2 regulatory mechanisms.

L'associazione tra fumo di tabacco e crisi economiche in Italia.

OBJECTIVES: to analyse the association between smoking behaviour and economic crises in Italy between 1993 and 2015. DESIGN: ecological study, carried out on data of the Italian National Institute of Statistics, by means of fixed-effect panel regressions. SETTING AND PARTICIPANTS: the rate of smoking prevalence (disaggregated by gender and age) and the unemployment rate (disaggregated by gender and referring to individuals aged 15 or more) were collected for each of the twenty Italian regions. Also, percentage fluctuations of the national real gross domestic product (GDP) were collected to identify the years of severe economic crisis. MAIN OUTCOME MEASURES: number of people who smoke per 100 people with the same features. RESULTS: among men, increased regional unemployment rate was associated with increased smoking behaviour only in the group aged 25-34 years. Differently, severe economic crises were associated with increased smoking in almost all age groups, except for men aged 15-24 years. A 1-point decrease in GDP was associated with 0.75 more smokers aged 15 years or more. The highest coefficient was reported among men aged 35-44 years, where a 1-point decrease in GDP was associated with 1.16 more smokers (every 100 men). This age group is also featured by the second highest prevalence of tobacco smoking (36.8%). Among women, a 1-point increase in the regional unemployment rate was associated with 0.08 less smokers every 100 women. Similarly, periods of severe economic crisis at national level were associated with reduced smoking behaviour among women aged 15 years or more, specifically those aged 15-24 years. Differently, women aged 25-34 and 65 years or more showed an association similar to that reported among men. In these groups, a 1-point decrease in GDP was associated with 0.67 and 1.08 more smokers every 100 women. While among the latter the prevalence of tobacco smoking is the lowest, among the former it is the third highest prevalence (21.69%). Therefore, increased smoking behaviour due to economic crises seems to occur especially among women aged 25-35 years old, as happens among men. CONCLUSIONS: men in almost all age groups and women aged 25-34 and 65 years or more represent vulnerable groups in which smoking behaviour may increase in times of economic hardship. Therefore, specific policies should be implemented to prevent this occurrence, as well as the negative health outcomes of tobacco smoking.

Empathy and perceived burden in caregivers of patients with schizophrenia spectrum disorders.

BACKGROUND: Caregivers of patients load different kinds of burdens, including emotional distress. Aims of this study were to evaluate both burden and empathy of caregivers who assist patients with schizophrenia spectrum disorders. METHODS: We selected a sample of 60 caregivers (34 women and 26 men), who assisted patients with schizophrenia spectrum disorders treated in our local Community Mental Health Center for a 1-year minimum period. We administered two scales to our sample, Zarit Burden Interview (ZBI) and Balanced Emotional Empathy Scale (BEES), and collected data of caregivers and their assisted patients in a 3-month period. Data were statistically analyzed. RESULTS: We reported a mean ZBI score of 49.68 (±15.03 SD) and a mean BEES score of 14.35 (±9.05 SD), indicating the perception of moderate-severe burden and low level of empathy, respectively. The analysis of internal consistency confirmed the good reliability of both ZBI (Cronbach's alpha = 0.90) and BEES (Cronbach's alpha = 0.77). The correlation between the two scales was not statistically significant at Spearman test. At our multiple linear regression, many variables of both caregiver and patient showed a significant correlation with the ZBI score. In particular, not living with the assisted patient and female gender of caregiver potentially decreased the burden, whereas clinical severity of assisted patient and two caregiver conditions, middle school education and spouse relationship with patient, could worsen the burden. We highlighted two positive statistically significant correlations between the total score of BEES and caregiver characteristics: being spouse and not living with assisted patient. CONCLUSIONS: Our study highlights that the caregiver burden of patients with severe psychiatric disorders is high and is associated with low emotional empathy experienced by caregivers, probably due to a defensive psychological mechanism. The conditions of spouse and cohabitation can concomitantly increase both empathy and burden in caregivers.

Hypokalemia in Patients with COVID-19.

BACKGROUND: Patients with COVID-19 experience multiple clinical conditions that may cause electrolyte imbalances. Hypokalemia is a concerning electrolyte disorder closely associated with severe complications. This study aimed to estimate prevalence, risk factors and outcome of hypokalemia in a cohort of patients with confirmed COVID-19. METHODS: A retrospective analysis was conducted on 290 non-ICU admitted patients with COVID-19 at the tertiary teaching hospital of Modena, Italy, from February 16 to April 14, 2020. RESULTS: Hypokalemia was detected in 119 out of 290 patients (41%) during hospitalization. Mean serum potassium was 3.1 ± 0.1 meq/L. The majority of patients (90.7%) patients experienced only a mild decrease in serum potassium level (3-3.4 mEq/L). Hypokalemia was associated with hypocalcemia, which was detected in 50% of subjects. Urine potassium-to-creatinine ratio, measured in a small number of patients (n = 45; 36.1%), revealed an increase of urinary potassium excretion in most cases (95.5%). Risk factors for hypokalemia were female sex (odds ratio (OR) 2.44; 95% CI 1.36-4.37; P 0.003) and diuretic therapy (OR 1.94, 95% CI 1.08-3.48; P 0.027). Hypokalemia, adjusted for sex, age and SOFA score, was not associated with ICU transfer (OR 0.52; 95% CI 0.228-1.212; P = 0.131), in-hospital mortality (OR, 0.47; 95% CI 0.170-1.324; P = 0.154) and composite outcome of ICU transfer or in-hospital mortality (OR 0.48; 95% CI 0.222-1.047; P = 0.065) in our cohort of patients. CONCLUSIONS: Hypokalemia was a frequent disorder in subjects with COVID-19. Female sex and diuretic therapy were identified as risk factors for low serum potassium levels. Hypokalemia was unrelated to ICU transfer and death in this cohort of patients.

How Altered Ribosome Production Can Cause or Contribute to Human Disease: The Spectrum of Ribosomopathies.

A number of different defects in the process of ribosome production can lead to a diversified spectrum of disorders that are collectively identified as ribosomopathies. The specific factors involved may either play a role only in ribosome biogenesis or have additional extra-ribosomal functions, making it difficult to ascribe the pathogenesis of the disease specifically to an altered ribosome biogenesis, even if the latter is clearly affected. We reviewed the available literature in the field from this point of view with the aim of distinguishing, among ribosomopathies, the ones due to specific alterations in the process of ribosome production from those characterized by a multifactorial pathogenesis.

Waiting time information in the Italian NHS: A citizen perspective.

Public involvement in the management and communication of waiting times is known to support initiatives to reduce waiting times, as well as increase fairness and promote transparency and accountability. In order to improve transparency and communication to citizens, Italy recently updated the National Regulatory Plan for Waiting Lists (2019-2021), which calls for the disclosure of waiting time information on healthcare provider webpages. This study analyses waiting time information for outpatient visits and digital services available on the institutional website pages of 144 public healthcare organisations in nine regions and two autonomous provinces of Italy. Web pages were analysed both in terms of the available information/services, using a grid, and in terms of the quality of the text using an advanced readability assessment tool (READ-IT). This information was complemented and validated by regional healthcare key informants during research-specific workshops. Waiting time information disclosure, digital services and text readability varied both within and between the regional healthcare systems and organisations. The types and characteristics of waiting time information and statistics vary considerably with a negative impact on their use for benchmarking and their readability and usability for booking purposes. Overall, communication weaknesses due to low harmonization and clarity of information can undermine efforts in effectively informing and involving the public through online waiting time data disclosure.

Impact of sialyltransferase ST6GAL1 overexpression on different colon cancer cell types.

Cancer-associated glycan structures can be both tumor markers and engines of disease progression. The structure Siaα2,6Galß1,4GlcNAc (Sia6LacNAc), synthesized by sialyltransferase ST6GAL1, is a cancer-associated glycan. Although ST6GAL1/Sia6LacNAc are often overexpressed in colorectal cancer (CRC), their biological and clinical significance remains unclear. To get insights into the clinical relevance of ST6GAL1 expression in CRC, we interrogated The Cancer Genome Atlas with mRNA expression data of hundreds of clinically characterized CRC and normal samples. We found an association of low ST6GAL1 expression with microsatellite instability (MSI), BRAF mutations and mucinous phenotype but not with stage, response to therapy and survival. To investigate the impact of ST6GAL1 expression in experimental systems, we analyzed the transcriptome and the phenotype of the CRC cell lines SW948 and SW48 after retroviral transduction with ST6GAL1 cDNA. The two cell lines display the two main pathways of CRC transformation: chromosomal instability and MSI, respectively. Constitutive ST6GAL1 expression induced much deeper transcriptomic changes in SW948 than in SW48 and affected different genes in the two cell lines. ST6GAL1 expression affected differentially the tyrosine phosphorylation induced by hepatocyte growth factor, the ability to grow in soft agar, to heal a scratch wound and to invade Matrigel in the two cell lines. These results indicate that the altered expression of a cancer-associated glycosyltransferase impacts the gene expression profile, as well as the phenotype, although in a cancer subtype-specific manner.

Stakeholders' views on vocational rehabilitation programs: a call for collaboration with Occupational Health Physicians.

BACKGROUND: The triple-dip recession taking place in Italy in 2008-2014 impacted negatively on health, mainly by increasing the rate of unemployment. This increased the prevalence of mental health disorders, while reducing the number of available places on vocational rehabilitation programs (VRPs) delivered by the psychiatric services. OBJECTIVES: To explore the different points of views of stakeholders (namely, users and professionals) involved in VRPs developed inside an Italian Community Mental Health Center (CMHC). METHODS: A sample of users, psychiatrists, educators and nurses of an Italian CMHC involved in VRPs took part in a focus group. Content analysis was performed with MAXQDA 12, by developing a hierarchical code system a posteriori (i.e., derived from the data). The respondent validation phase was carried out by means of a multiple-choice questionnaire, administered to all participants. RESULTS: A total of 86 emerging issues were coded, divided into two macro-areas: Positive and Negative Reinforcements (48 contributions, 56%, and 38 contributions, 44%, respectively), further subdivided into three areas: professional (service) factors, personal (i.e, user-related) factors, and work environment features (including relationships in the workplace). Some contributions raised issues concerning occupational health protection (e.g. need of information about the rights and duties of the users-workers, as well as the risks they are exposed to in the workplace). CONCLUSIONS: The analysis suggested to address specific issues concerning work and VRPs by means of psycho-education group interventions currently carried out at CMHCs, and pointed to the need to foster collaboration between mental health professionals and the occupational health physician of the company where the VRP is started and where the user might be employed.