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

Comparative effectiveness of conservative and pharmacological interventions for chronic non-specific neck pain : Protocol of a systematic review and network meta-analysis

BACKGROUND: Neck Pain (NP) has been ranked as one of the top chronic pain conditions in terms of prevalence and years lived with disability in the latest Global Burden of Disease. NP has remarkable socio-economic consequences however, research efforts are limited. Discrepancies among guidelines recommendations on management of chronic neck pain exist. The purpose of this study protocol is to provide the methods for a review with network meta-analysis to identify the most effective interventions for chronic neck pain. METHODS: The following databases will be searched from their inception to February 2019: Cochrane Controlled Trials Register (CENTRAL), PubMed, CINAHL, Scopus, ISI Web of Science and PEDro.Randomized controlled trials (RCTs) on pharmacological and not pharmacological interventions will be included and their risk of bias will be evaluated using the Cochrane Risk of bias tool. Primary outcomes will be reduction in pain and disability. A network meta-analysis will be carried out and pairwise meta-analysis will be conducted using Stata 15 software. Grading of recommendations assessment, development, and evaluation (GRADE) will be applied to assess quality of the body of the evidence. RESULTS: The results of this review will be submitted to a peer-review journal for publication. CONCLUSION: This network meta-analysis will provide a comprehensive review on the most effective treatments for the management of chronic neck pain providing key evidence-based information to patients, clinicians and other relevant stakeholders. Registration: PROSPERO (registration number CRD42019124501)

Anthelmintic activity of Stevia aristata extract on Echinococcus granulosus: in vitro and in vivo study

Cystic echinococcosis (CE) is a worldwide zoonotic disease caused by Echinococcus granulosus, which produces long-term infections in humans and animals. Available anti-parasitic treatment against CE is mostly limited to the use of benzimidazoles, mainly albendazole (ABZ). However, it has undesirable side effects and their efficacy is about 50%. Based on the problematic described, new treatment alternatives are urgently needed. Plants from the Stevia genus (Asteraceae) are a potential source of anti-protozoal and anti-microbial compounds. The aim of the present study was to evaluate the in vitro and in vivo efficacy of the Stevia aristata dichloromethane extract against E. granulosus. Viable and free protoscoleces or cysts were treated with 100, 50, 10 and 5 μg/ml of the extract. Viability assessment using the methylene blue exclusion test and scanning electron microscopy (SEM) (for protoscoleces) or evaluation of germinal layer collapse (for cysts) was performed. CF-1 mice (n=30) infected with E. granulosus were allocated into the following experimental groups (6 months post-infection): (1) Control, (2) ABZ 25 mg/kg, every 24 h for 30 days; (3) S. aristata 50 mg/kg, every 24 h for 23 days. At the end of the treatment the weight of the cysts was recorded and samples were analysed by SEM. Protoscoleces viability decreased quickly with 100 µg/ml, reaching 0% after 20 days of treatment. After 4 days of incubation, the collapse of the germinal layer was observed in 60 ± 5.8% and 83.3 ± 12.0% of cysts treated with 50 and 100 µg/ml, respectively. Whilst ultrastructural damage was observed in the cysts obtained from S. aristata or ABZ treated mice, no significant differences in the weight of the cysts were obtained (P > 0.05). In conclusion, S. aristata treatment caused high protoscolicidal and cysticidal effects, but not significant reduction in the weight of the cysts in experimentally infected mice.Fil: Albani, Clara Maria. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; ArgentinaFil: Borgo, Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Fabbri, Julia. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; ArgentinaFil: Pensel, Patricia Eugenia. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; ArgentinaFil: Fasciani, Lara. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; ArgentinaFil: Hernandez, N.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacognosia; ArgentinaFil: Paladini, A.. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biología. Laboratorio de Zoonosis Parasitarias; ArgentinaFil: Sülsen, Valeria Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Elissondo, María Celina. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; ArgentinaLXVI Annual Meeting of Sociedad Argentina de Investigación Clínica (SAIC); LXIX Annual Meeting of Sociedad Argentina de Inmunología (SAI); LIII Annual Meeting of Asociación Argentina de Farmacología Experimental (AAFE) y XI Annual Meeting of Asociación Argentina de Nanomedicinas (NANOMED-AR)ArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaAsociación Argentina de NanomedicinasAsociación Argentina de Farmacología Experimenta

po 298 myc favours the onset of tumour initiating cells by inducing epigenetic reprogramming of mammary epithelial cells towards a stem cell like state

Introduction Breast cancer consists of highly heterogenous tumours whose cell of origin resulted difficult to be defined. Recent findings highlighted the possibility that tumor-initiating cells (TICs) may arise from dedifferentiation of lineage-committed cells, by reactivation of multipotency in response to oncogenic insults. MYC is the most frequently amplified oncogene in breast cancer and the activation of MYC pathway has been associated with the basal-like subtype, which is characterised by poor survival and lack of a specific therapeutic strategy. Although MYC has been considered a driver oncogene in breast cancer, its mechanism of action in tumour initiation has been poorly addressed. Material and methods To evaluate the role of MYC in perturbing cell identity of somatic cells, we transduced hTERT-immortalised human mammary epithelial cells (IMEC) with a retroviral vector expressing low levels of the exogenous c-Myc. The effect of MYC overexpression was evaluated by performing morphological analysis and gene expression profiling. To verify whether MYC overexpression could enrich for cells with functional stem cell-like properties, we performed mammospheres assay. ChIP-seq analyses were performed to profile chromatin modifications and MYC binding in IMEC WT, -MYC and mammospheres. To determine whether MYC-reprogrammed IMEC were enriched for TICs, we performed in vivo injection in NOD/SCID mice and assessed long-term tumorigenic potential by performing serial transplantation assay. To assess the clinical relevance of our findings, we investigated the expression of MYC-dependent oncogenic signature in a database of breast cancer patients. Results and discussions Overexpression of MYC induces transcriptional repression of lineage-specifying transcription factors, causing decommissioning of luminal-specific enhancers. Of note, MYC-driven dedifferentiation supports the onset of a basal/stem cell-like state by inducing the activation of de novo enhancers, which drive the transcriptional activation of oncogenic pathways. MYC-driven epigenetic reprogramming favours the formation and maintenance of TICs endowed with metastatic capacity. Moreover, oncogenic pathways activated by MYC-modulated enhancers are associated with basal-like breast cancer in patients with a poor prognosis. Conclusion MYC-driven tumour initiation relies on a cell reprogramming process, which is mediated by activation of MYC-dependent oncogenic enhancers, thus establishing a therapeutic rational for treating basal-like breast cancers

Ocular involvement in hereditary transthyretin amyloidosis: A case series describing novel potential biomarkers

Hereditary transthyretin amyloidosis (hATTR) is a rare disease caused by a point mutation in the transthyretin (TTR) gene and inherited in an autosomal dominant fashion. TTR is a plasma protein that functions as a carrier for thyroxine (T4) and retinol (vitamin A). Ophthalmological manifestations are due to both the hepatic and ocular production of mutated TTR. In this case series, we report the ocular manifestations of hATTR in eighteen eyes of nine consecutive patients. Corneal nerve abnormalities as well as morphological and functional changes in the retina were investigated. The study was a single-center, retrospective, observational, clinical case series. In all patients, corneal confocal microscopy (CCM), multimodal imaging of the retina, including fundus photography and Optical Coherence Tomography (OCT), as well as rod and cone electroretinography (ERG) were performed. Eight patients had active disease and one was an unaffected carrier. In all study eyes, corneal nerve plexa examined with CCM were poorly represented or absent. Mixed rod-cone and cone ERG b-wave amplitudes were reduced, and photopic b-wave responses were significantly delayed. Photopic Negative Response (PhNR) amplitude was significantly reduced, while PhNR latency was significantly augmented. In 13/18 eyes, vitreous opacities and abnormalities of vitreo-retinal interface were found. The current results highlight the presence of corneal nerve damage. Functional retinal abnormalities, detected by ERG, can be found even in the presence of minimal or absent structural retinal damage. These findings support the use of CCM and ERGs to detect early biomarkers for primary hATTR

Design and Characterization of a Human Monoclonal Antibody that Modulates Mutant Connexin 26 Hemichannels Implicated in Deafness and Skin Disorders

Background: Mutations leading to changes in properties, regulation, or expression of connexin-made channels have been implicated in 28 distinct human hereditary diseases. Eight of these result from variants of connexin 26 (Cx26), a protein critically involved in cell-cell signaling in the inner ear and skin. Lack of non-toxic drugs with defined mechanisms of action poses a serious obstacle to therapeutic interventions for diseases caused by mutant connexins. In particular, molecules that specifically modulate connexin hemichannel function without affecting gap junction channels are considered of primary importance for the study of connexin hemichannel role in physiological as well as pathological conditions. Monoclonal antibodies developed in the last three decades have become the most important class of therapeutic biologicals. Recombinant methods permit rapid selection and improvement of monoclonal antibodies from libraries with large diversity.Methods: By screening a combinatorial library of human single-chain fragment variable (scFv) antibodies expressed in phage, we identified a candidate that binds an extracellular epitope of Cx26. We characterized antibody action using a variety of biochemical and biophysical assays in HeLa cells, organotypic cultures of mouse cochlea and human keratinocyte-derived cells.Results: We determined that the antibody is a remarkably efficient, non-toxic, and completely reversible inhibitor of hemichannels formed by connexin 26 and does not affect direct cell-cell communication via gap junction channels. Importantly, we also demonstrate that the antibody efficiently inhibits hyperative mutant Cx26 hemichannels implicated in autosomal dominant non-syndromic hearing impairment accompanied by keratitis and hystrix-like ichthyosis-deafness (KID/HID) syndrome. We solved the crystal structure of the antibody, identified residues that are critical for binding and used molecular dynamics to uncover its mechanism of action.Conclusions: Although further studies will be necessary to validate the effect of the antibody in vivo, the methodology described here can be extended to select antibodies against hemichannels composed by other connexin isoforms and, consequently, to target other pathologies associated with hyperactive hemichannels. Our study highlights the potential of this approach and identifies connexins as therapeutic targets addressable by screening phage display libraries expressing human randomized antibodies

Digital phonology: systemic perspectives

In this chapter we discuss the study of phonology (of speech, and other semiotic resources with sound as expression plane, such as music) within the environments of contemporary software resources, including a software platform currently under development. These software tools enable researchers and teachers to readily access the sound signal and create a variety of annotations of such data, and to store, search, process and display the data and their analyses. Such resources thus make possible the correlation, in both the database and interface, of phonetic, phonological, lexicogrammatical, semantic and contextual analyses within different metafunctions, at different ranks and so on. The present chapter is not a review of software applications as such, but rather a discussion of some of the affordances of and issues in the development and use of digital technologies (for a review of software resources relevant to systemic scholars see O\u27Donnell and Bateman, 2005)

Reaction of Singlet Oxygen with Thioanisole in Ionic Liquid-Acetonitrile Binary Mixtures

A study of the reaction of thioanisole with singlet oxygen in different ionic liquid acetonitrile binary mixtures has shown that ILs are able to accelerate the thioanisole sulfoxidation when used as additives. With imidazolium ILs, the maximum efficiency is reached at X-IL similar to 0.1-0.2, whereas for the pyrrolidinium IL a plateau is reached. These results are discussed in terms of the ILs' tendency to form ionic aggregates and of differences in sulfoxidation reaction mechanism