Ultrasound-guided transvaginal radiofrequency ablation of uterine fibroids assisted by virtual needle tracking system : a preliminary study

Purpose: The purpose of this study was to assess the feasibility and outcome of transvaginal ultrasound (US)-guided radiofrequency ablation of uterine fibroids assisted by a real-time virtual needle tracking (VT) system. Methods: Between January 2017 and February 2018, 19 patients (age 45 \ub1 8 y, range 36\u201353 y) with 25 symptomatic uterine fibroids underwent transvaginal radiofrequency ablation (RFA) at a single center. Mean number of fibroids for patient was 1.7 (min, max: 1\u20133). Patients with more than one fibroid were 10 (52.6%). Uterine fibroids (mean volume: 13.6 mL; range: 5.3\u201341.9 mL) were treated with a dedicated internally cooled 17 G 35 cm RF needle with 1 cm or variable active tip and the moving shot technique. An electromagnetic system was used for showing a virtual needle during the procedure. Contrast-enhanced ultrasound evaluation was performed before and immediately at the end of procedure. Feasibility of the procedure, technical success rate, volume percentage reduction at 1, 3 and 6 months, clinical outcome (QOL score) and complications were analyzed. Results: Procedure was feasible in 19/19 patients (100%). Technical success was achieved in 100% of 25 treated fibroids. Mean fibroids volume decreased from 13.6 ml at baseline to 5.9 ml at 6 month (reduction rate 62.7%, range 48.5\u201376.9; p <.05). No major immediate or late complications occurred. Minor complications occurred in two patients. QOL score significantly improved from 68 \ub1 36 at baseline to 97 \ub1 16 at six-months follow-up (p <.05). Conclusion: Transvaginal US-guided RFA assisted by a real-time VT system is a feasible, safe and effective technique for the treatment of uterine fibroids

Family caregiver emotional distress in advanced cancer : the DME- C scale psychometric properties

Publisher Copyright: © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Family caregivers of patients with advanced illness at end of life often report high levels of emotional distress. To address this emotional distress is necessary to have adequate and reliable screening tools. Aim: This study analyses the psychometric properties and clinical utility of the Family Caregiver Emotional Detection Scale for caregivers of patients with end-stage cancer (DME-C, Spanish acronym) who are receiving palliative care (PC). Design: Multicentre, cross-sectional study. Settings/participants: Family caregivers of patients with advanced cancer at end of life receiving palliative treatment were interviewed to explore their emotional distress through the DME-C scale and other instruments measuring anxiety and depression (Hospital Anxiety and Depression Scale (HADS)), distress thermometer (DT) and overload (B), as well as a clinical psychological assessment (CPA). Results: 138 family caregivers, 85 (61.6%) female and 53 (38.4%) male, with an average age of 59.69±13.3 participated in the study. The reliability of the scale, as measured by Cronbach's alpha, was 0.76, and its stability over time was 0.734. Positive, significant correlations were found between the DME-C and the scores for anxiety and depression registered on the HADS scale, as well as with the total result of this latter scale and the results for B, the DT and the CPA. A statistical analysis of the receiver-operating characteristic curves showed that the scale has a sensitivity and specificity of 75%, and that the cut-off point for the detection of emotional distress was a score ≥11. Fifty-four per cent of the caregivers displayed emotional distress according to this scale. Conclusions: The DME-C displays good psychometric properties. It is simple, short, reliable and easy to administer. We believe that the instrument is useful for the detection of emotional distress in the family caregivers of hospitalised patients suffering from end-stage illnesses and receiving PC

Abnormal Splicing of NEDD4 in Myotonic Dystrophy Type 2 Possible Link to Statin Adverse Reactions

Myotonic dystrophy type 2 (DM2) is a multisystemic disorder caused by a (CCTG)n repeat expansion in intron 1 of CNBP. Transcription of the repeats causes a toxic RNA gain of function involving their accumulation in ribonuclear foci. This leads to sequestration of splicing factors and alters pre-mRNA splicing in a range of downstream effector genes, which is thought to contribute to the diverse DM2 clinical features. Hyperlipidemia is frequent in DM2 patients, but the treatment is problematic because of an increased risk of statin-induced adverse reactions. Hypothesizing that shared pathways lead to the increased risk, we compared the skeletal muscle expression profiles of DM2 patients and controls with patients with hyperlipidemia on statin therapy. Neural precursor cell expressed, developmentally downregulated-4 (NEDD4), an ubiquitin ligase, was one of the dysregulated genes identified in DM2 patients and patients with statin-treated hyperlipidemia. In DM2 muscle, NEDD4 mRNA was abnormally spliced, leading to aberrant NEDD4 proteins. NEDD4 was down-regulated in persons taking statins, and simvastatin treatment of C2C12 cells suppressed NEDD4 transcription. Phosphatase and tensin homologue (PTEN), an established NEDD4 target, was increased and accumulated in highly atrophic DM2 muscle fibers. PTEN ubiquitination was reduced in DM2 myofibers, suggesting that the NEDD4-PTEN pathway is dysregulated in DM2 skeletal muscle. Thus, this pathway may contribute to the increased risk of statin-adverse reactions in patients with DM2

(CCUG)n RNA toxicity in a Drosophila model of myotonic dystrophy type 2 (DM2) activates apoptosis

The myotonic dystrophies are prototypic toxic RNA gain-of-function diseases. Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are caused by different unstable, noncoding microsatellite repeat expansions - (CTG)DM1 in DMPK and (CCTG)DM2 in CNBP Although transcription of mutant repeats into (CUG)DM1 or (CCUG)DM2 appears to be necessary and sufficient to cause disease, their pathomechanisms remain incompletely understood. To study the mechanisms of (CCUG)DM2 toxicity and develop a convenient model for drug screening, we generated a transgenic DM2 model in the fruit fly Drosophila melanogaster with (CCUG)n repeats of variable length (n=16 and 106). Expression of noncoding (CCUG)106, but not (CCUG)16, in muscle and retinal cells led to the formation of ribonuclear foci and mis-splicing of genes implicated in DM pathology. Mis-splicing could be rescued by co-expression of human MBNL1, but not by CUGBP1 (CELF1) complementation. Flies with (CCUG)106 displayed strong disruption of external eye morphology and of the underlying retina. Furthermore, expression of (CCUG)106 in developing retinae caused a strong apoptotic response. Inhibition of apoptosis rescued the retinal disruption in (CCUG)106 flies. Finally, we tested two chemical compounds that have shown therapeutic potential in DM1 models. Whereas treatment of (CCUG)106 flies with pentamidine had no effect, treatment with a PKR inhibitor blocked both the formation of RNA foci and apoptosis in retinae of (CCUG)106 flies. Our data indicate that expression of expanded (CCUG)DM2 repeats is toxic, causing inappropriate cell death in affected fly eyes. Our Drosophila DM2 model might provide a convenient tool for in vivo drug screening

New professions for academic research libraries

La sezione "Note e discussioni" di questo numero di AIB studi offre una prima riflessione sui profili professionali emergenti nella biblioteca accademica di ricerca. I quattro contributi di Sada, Sirito e Gregori, Morando, Minsenti e Gargiulo – preceduti da una nota introduttiva di Maria Cassella sul nuovo ruolo della biblioteca accademica di ricerca – esplorano alcuni di questi profili professionali a partire dagli interventi presentati in occasione di un seminario di studio organizzato a Roma nel novembre 2012.Ellis Sada, Liliana Gregori e Paolo Sirito affermano la necessità che gli operatori di biblioteca a tutti i livelli non si limitino più soltanto a un ruolo passivo nel ciclo della conoscenza (selezione, acquisizione e distribuzione dei contenuti) ma diventino parte attiva del ciclo stesso. Maddalena Morando analizza la figura del repository manager, il cui compito consiste nella pianificazione e gestione dell'Institutional Repository (IR) come vetrina della produzione scientifica di ateneo, e cerca di calare le buone pratiche internazionali nella realtà universitaria italiana. Pierfranco Minsenti ci parla invece del coordinatore dei servizi informativi online (o responsabile della gestione di un portale). Il portale, inteso non come semplice piattaforma tecnologica ma come servizio, presuppone infatti una nuova e più stretta integrazione tra attività di back-office (gestione dei sistemi, creazione di metadati, gestione delle risorse elettroniche ecc.) e di front-office (fornitura di documenti, assistenza nell’accesso alle risorse elettroniche). Per finire, Paola Gargiulo delinea le competenze umane e professionali richieste all'electronic resources librarian, il bibliotecario addetto all'acquisizione, gestione, manutenzione, organizzazione e accesso delle risorse informative elettroniche.The Note e discussioni's section of the journal's current issue focuses on the new professional profiles for academic research libraries. All the papers included in this section were presented during a workshop held in Rome in November 2012, and are introduced by a preliminary note by Maria Cassella on the new role of academic research library.Ellis Sada, Liliana Gregori and Paolo Sirito claim the necessity, for information professional, to be no longer passively engaged in the cycle of knowledge (e.g. by the mere selection, acquisition and distribution of content) but to became an active part of the very same cycle too. Maddalena Morando analyses the repository manager's professional profile, whose job is the planning and management of the Institutional Repository (IR) as a showcase of the university's scientific production. She also tries to imagine which good practices could be adapted from the existing literature to the context of Italian universities. Pierfranco Minsenti gives an effective account of what a coordinator of online information services (i.e. the person in charge of the web-based library portal) does: the management of a library portal – not just a technological platform, but an actual service – requires improved synergies among back-office activities (such as systems management, metadata creation, electronic resources management) and front-office activities (such as document delivery and assistance in accessing electronic resources). Finally, Paola Gargiulo describes the core competencies and abilities of the electronic resources librarian, who covers all the activities related to the acquisition, licensing, management of ER

Regulation of CEACAM1 transcription in human breast epithelial cells

<p>Abstract</p> <p>Background</p> <p>Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is a transmembrane protein with multiple functions in different cell types. CEACAM1 expression is frequently mis-regulated in cancer, with down-regulation reported in several tumors of epithelial origin and <it>de novo </it>expression of CEACAM1 in lung cancer and malignant melanoma. In this report we analyzed the regulation of CEACAM1 expression in three breast cancer cell lines that varied in CEACAM1 expression from none (MCF7) to moderate (MDA-MB-468) to high (MCF10A, comparable to normal breast).</p> <p>Results</p> <p>Using <it>in vivo </it>footprinting and chromatin immunoprecipitation experiments we show that the <it>CEACAM1 </it>proximal promoter in breast cells is bound in its active state by SP1, USF1/USF2, and IRF1/2. When down-regulated the <it>CEACAM1 </it>promoter remains accessible to USF2 and partially accessible to USF1. Interferon-γ up-regulates CEACAM1 mRNA by a mechanism involving further induction of IRF-1 and USF1 binding at the promoter. As predicted by this analysis, silencing of IRF1 and USF1 but not USF2 by RNAi resulted in a significant decrease in CEACAM1 protein expression in MDA-MB-468 cells. The inactive <it>CEACAM1 </it>promoter in MCF7 cells exhibits decreased histone acetylation at the promoter region, with no evidence of H3K9 or H3K27 trimethylation, histone modifications often linked to condensed chromatin structure.</p> <p>Conclusions</p> <p>Our data suggest that transcription activators USF1 and IRF1 interact to modulate CEACAM1 expression and that the chromatin structure of the promoter is likely maintained in a poised state that can promote rapid induction under appropriate conditions.</p

Desarrollo de la escala EDSOL para la detección de la soledad existencial en enfermos al final de la vida

Objetivo: Presentar el desarrollo de la escala de detección de la soledad existencial (EDSOL) en personas con enfermedades avanzadas en tratamiento paliativo. Método: Se describe el proceso de elaboración de la escala Detección de la Soledad Existencial EDSOL. Para ello, 1) se ha revisado la bibliografía existente sobre el tema; 2) se ha establecido un marco teórico de referencia; 3) se han definido los criterios que debía cumplir el instrumento de cribado; y 4) se ha consultado con expertos y enfermos la adecuación de los ítems de la escala. Resultados: Se presenta a la escala EDSOL, que consta de dos partes: 1) tres preguntas dirigidas a los enfermos; y 2) diferentes observaciones realizadas por el personal sanitario acerca de la presencia de signos externos de soledad existencial. La escala final fue revisada por enfermos y profesionales. Conclusión: La escala EDSOL es una herramienta apropiada para identificar la presencia de Soledad Existencial en pacientes al final de la vida. En este caso, se propondrá su uso sistemático en la detección temprana de la Soledad Existencial y la implementación de intervenciones asistenciales específicasAim: This paper presents the development of Detection of Existential Loneliness Scale (EDSOL) of patients with advanced disease/terminal illness that receiving palliative care. Method: The process of preparing the scale is described. For this: 1) the literature on the subject has been revised, 2)theoretical framework has been established, 3) it has been defined the criteria to be met by the screening tool, and 4) the final scale was reviewed by patients and experts. Results: The EDSOL scale consists of two parts: 1) three questions addressed to patients and; 2) several questions addressed to health staff about the observation of external signs of Existential Loneliness. The final scale was reviewed by patients and experts (facie validity) showing good validity. Conclussion: The EDSOL scale will be an appropriate tool for identifying the Existential Loneliness of patients at the end of life or advanced illness. In this case, we will propose the systematic use of EDSOL for early detection and specific interventions on existential loneliness experience

Cellular and viral chromatin proteins are positive factors in the regulation of adenovirus gene expression

The adenovirus genome forms chromatin-like structure with viral core proteins. This complex supports only a low level of transcription in a cell-free system, and thus core proteins have been thought to be negative factors for transcription. The mechanism how the transcription from the viral DNA complexed with core proteins is activated in infected cells remains unclear. Here, we found that both core proteins and histones are bound with the viral DNA in early phases of infection. We also found that acetylation of histone H3 occurs at the promoter regions of viral active genes in a transcription-independent manner. In addition, when a plasmid DNA complexed with core proteins was introduced into cells, core proteins enhanced transcription. Knockdown of TAF-I, a remodeling factor for viral core protein–DNA complexes, reduces the enhancement effect by core proteins, indicating that core proteins positively regulate viral transcription through the interaction with TAF-I. We would propose a possible mechanism that core proteins ensure transcription by regulating viral chromatin structure through the interaction with TAF-I