Past, Present, and Future Strategies for Enhanced Assessment of Embryo's Genome and Reproductive Competence in Women of Advanced Reproductive Age

Recent advancements in genomic analysis allow testing of an increasing number of genetic features in human preimplantation embryos. Typical single gene mutation and whole chromosomes testing can now be integrated with assessment of mitochondrial DNA and polygenic conditions. Diagnostic expansion into epigenetic and transcriptomic assessment in the near future are potential technological targets which may improve the prognostic outlook of patients of advanced reproductive age and overall in vitro fertilization (IVF) treatment outcomes. In this review, we discuss the technological progress of recent years and their future applications in preimplantation genetic testing in IVF

Assessment of ascending aorta distensibility after successful coarctation repair by strain Doppler echocardiography

BACKGROUND: Increased arterial stiffness may participate in the genesis of hypertension and increase of left ventricular (LV) mass after surgical correction of coarctation of the aorta. The purpose of the current study was to assess the aortic elastic properties using Doppler tissue imaging and strain rate imaging in patients after coarctoplasty. METHODS: Echocardiography with Doppler tissue/strain rate imaging capabilities was performed in 26 adult normotensive patients who had successful repair of coarctation of the aorta in infancy and in 24 control subjects. Transesophageal aortic transverse sections were imaged at the level of the proximal and distal segments to the repair site. Doppler tissue imaging wall velocities during systole (S(w)), early relaxation (E(w)), and atrial systole (A(w)) and peak systolic strain (ps epsilon) were measured in both groups. Transthoracic ascending aorta (AAo) measurements were also obtained. RESULTS: In the patients with coarctoplasty, S(w) velocities and ps epsilon were significantly decreased in the proximal segments compared with control subjects. Both peak systolic blood pressure after exercise (P < .001) and pulse pressure after exercise (P < .001) were directly related to AAo wall strain. LV annular early diastolic velocity was significantly reduced compared with control subjects in patients with decreased AAo wall strain and exercise-induced hypertension (P < .001) and related to AAo wall velocity (P < .005) and strain (P < .001). In multiple linear regression analysis, only weight, study group, and AAo wall strain were correlated to LV mass index. CONCLUSIONS: Patients with coarctation of the aorta have reduced proximal aortic wall velocities and strain and increased stiffness even after successful repair. This amplifies stress-induced hypertension and increases LV burden

Itch/β-arrestin2-dependent non-proteolytic ubiquitylation of SuFu controls Hedgehog signalling and medulloblastoma tumorigenesis

Suppressor of Fused (SuFu), a tumour suppressor mutated in medulloblastoma, is a central player of Hh signalling, a pathway crucial for development and deregulated in cancer. Although the control of Gli transcription factors by SuFu is critical in Hh signalling, our understanding of the mechanism regulating this key event remains limited. Here, we show that the Itch/β-arrestin2 complex binds SuFu and induces its Lys63-linked polyubiquitylation without affecting its stability. This process increases the association of SuFu with Gli3, promoting the conversion of Gli3 into a repressor, which keeps Hh signalling off. Activation of Hh signalling antagonises the Itch-dependent polyubiquitylation of SuFu. Notably, different SuFu mutations occurring in medulloblastoma patients are insensitive to Itch activity, thus leading to deregulated Hh signalling and enhancing medulloblastoma cell growth. Our findings uncover mechanisms controlling the tumour suppressive functions of SuFu and reveal that their alterations are implicated in medulloblastoma tumorigenesis

Itch/β-arrestin2-dependent non-proteolytic ubiquitylation of SuFu controls Hedgehog signalling and medulloblastoma tumorigenesis

Suppressor of Fused (SuFu), a tumour suppressor mutated in medulloblastoma, is a central player of Hh signalling, a pathway crucial for development and deregulated in cancer. Although the control of Gli transcription factors by SuFu is critical in Hh signalling, our understanding of the mechanism regulating this key event remains limited. Here, we show that the Itch/β-arrestin2 complex binds SuFu and induces its Lys63-linked polyubiquitylation without affecting its stability. This process increases the association of SuFu with Gli3, promoting the conversion of Gli3 into a repressor, which keeps Hh signalling off. Activation of Hh signalling antagonises the Itch-dependent polyubiquitylation of SuFu. Notably, different SuFu mutations occurring in medulloblastoma patients are insensitive to Itch activity, thus leading to deregulated Hh signalling and enhancing medulloblastoma cell growth. Our findings uncover mechanisms controlling the tumour suppressive functions of SuFu and reveal that their alterations are implicated in medulloblastoma tumorigenesis

Brentuximab vedotin as salvage treatment in Hodgkin lymphoma naïve transplant patients or failing ASCT: the real life experience of Rete Ematologica Pugliese (REP)

Brentuximab vedotin (BV) shows a high overall response rate (ORR) in relapsed/refractory (R/R) Hodgkin lymphoma (HL) after autologous transplant (ASCT). The aim of this multicenter study, conducted in nine Hematology Departments of Rete Ematologica Pugliese, was to retrospectively evaluate the efficacy and safety of BV as salvage therapy and as bridge regimen to ASCT or allogeneic transplant (alloSCT) in R/R HL patients. Seventy patients received BV. Forty-five patients (64%) were treated with BV as bridge to transplant:16 (23%) patients as bridge to ASCT and 29 (41%) as bridge to alloSCT. Twenty-five patients (36%), not eligible for transplant, received BV as salvage treatment. The ORR was 59% (CR 26%). The ORR in transplant naïve patients was 75% (CR 31%). In patients treated with BV as bridge to alloSCT, the ORR was 62% (CR 24%). In a multivariate analysis, the ORR was lower in refractory patients (p < 0.005). The 2y-OS was 70%. The median PFS was 17 months. Ten of the 16 (63%) naïve-transplant patients received ASCT, with 50% in CR before ASCT. In the 29 patients treated with BV as bridge to alloSCT, 28 (97%) proceeded to alloSCT with 25% in CR prior to alloSCT. The most common adverse events were peripheral neuropathy (50%), neutropenia (29%) and anemia (12%). These data suggest that BV is well tolerated and very effective in R/R HL, producing a substantial level of CR. BV may also be a key therapeutic agent to achieve good disease control before transplant, improving post- transplant outcomes, also in refractory and heavily pretreated patients, without significant overlapping toxicities with prior therapies

Proceedings of the 24th Paediatric Rheumatology European Society Congress: Part three

From Springer Nature via Jisc Publications Router.Publication status: PublishedHistory: collection 2017-09, epub 2017-09-0

Moda e Patrimonio Culturale/Fashion and Cultural Heritage

Nell’Anno Europeo per la salvaguardia e la valorizzazione del Patrimonio Culturale, ZoneModa Journal (ZMJ) ha dedicato un numero speciale al Patrimonio Culturale della Moda, un tema intrinsecamente complesso, ma di inestimabile ricchezza per la cultura e l’economia nazionale e internazionale. Il problema della conservazione, trasmissione e valorizzazione del patrimonio culturale è ormai al centro di importanti dibattiti internazionali e nazionali. Le politiche italiane, e più in generale dell’Unione Europea, forniscono specifiche linee guida di programmi da sviluppare mediante l’uso di tecnologie informatiche dedicate e del web, considerando soprattutto lo sviluppo delle Industrie Culturali Creative. Il patrimonio storico della moda in Italia è ingente, e dunque Università, Fondazioni, Enti territoriali si stanno organizzando per diffondere conoscenza, conservazione e valorizzazione di tale patrimonio, nei Paesi membri dell’Unione Europea ed extra Europa. Nel contempo, negli ultimi anni – ispirandosi alla propria storia, ma guardando al futuro – molte aziende italiane ed europee hanno reso i propri archivi strumenti di competitività aziendale nell’ambito della Brand Identity e dell’Heritage Marketing. Nonostante le numerose mostre organizzate negli ultimi anni, spesso proprio a partire dai materiali di archivio, tuttavia, è ancora difficile parlare di cultura della moda in Italia. Il peso della storia dell’arte, con la separazione tra arti minori e belle arti, accanto a una scarsa conoscenza delle dinamiche della moda al di là degli aspetti commerciali, evidenzia vecchi stereotipi che sembrano non tenere conto né dei cambiamenti avvenuti nel mondo dell’arte, né della complessità degli ambiti in cui la moda si trova ad agire. Questo numero della rivista dedicato alla moda e al patrimonio culturale vuole essere un contributo verso una maggiore consapevolezza della cultura e delle pratiche della moda nel XXI secolo.In the European Year for Safeguarding and Enhancing Cultural Heritage, ZoneModa Journal (ZMJ) has dedicated a special issue to the Cultural Heritage of Fashion, a theme that is intrinsically complex but of inestimable wealth for the national and international culture and economy. The problem of conservation, transmission and enhancement of cultural heritage is now at the centre of important international and national debates. Italian policies and more generally those of the European Union provide specific guidelines for programmes to be developed through the use of dedicated IT and web technologies, especially considering the development of Creative Cultural Industries. Fashion has an enormous historical heritage in Italy, and therefore universities, foundations and local authorities are organising to disseminate knowledge, conservation and enhancement of this heritage in the member countries of the European Union and beyond. At the same time, in the last few years — inspired by its own history, but looking to the future — many Italian and European companies have transformed their archives into tools of business competitiveness for Brand Identity and Heritage Marketing. This issue of the magazine dedicated to fashion and cultural heritage aims to be a contribution towards greater awareness of culture and culture fashion practices in the 21st century

Saggio introduttivo Moda e patrimonio culturale/Introductory essay Fashion and cultural heritage

Nel saggio introduttivo, in particolare nella sessione "patrimonio culturale e imprese moda" , viene svolta una riflessione sull'importanza che contenuti culturali, incluso il patrimonio storico, hanno per le imprese di moda italiane che operano nel mondo ipercompetitivo dell'economica globale. Il sistema moda italiano fa perno sull'esperienza storica di saperi e conoscenze, sedimentatesi attraverso generazioni di creativi e di esperienze distrettuali. Per la produzione di beni ad "alto valore simbolico", che includono prodotti dei più famosi brand di moda, il patrimonio culturale dell'impresa diventa così una parte fondamentale di quella che nel marketing si definisce "product concept", che contempla la totalità dei contenuti tangibili e intangibili, dove i secondi contemplano valori diretti quali l’immediato conferimento di status legato al bene, ma anche valori indiretti che l’impresa riesce a comunicare al consumatore attraverso la politica del brand. Il valore del patrimonio culturale, costituisce per le imprese di moda un legame emotivo coi propri clienti in quanto attraverso l’esperienza e la tradizione si qualifica la qualità del prodotto, il suo valore e il suo posizionamento in chiave storica. Il saggio introduttivo analizza quindi i progressi fatti in Italia negli anni recenti, per valorizzare il patrimonio culturale delle imprese,attraverso la valorizzazione del loro patrimonio culturale, ma anche il contributo che l'archeologia industriale, le fondazioni e i musi di moda hanno dato e stanno dando al territorio e alla valorizzazione del patrimonio artistico e culturale del Paese.In the introductory paper, specifically in the section "Cultural heritage and fashion companies", a reflection is held on the importance that cultural contents, including increase the value of historical heritage, have for Italian fashion companies operating in today's hyper-competitive world of the global economy. The italian fashion system is based on a historical experience, on the accumulation of knowledge through different generations of creatives and on district industrial systems. For the production of goods with “high symbolic value”, which include the products of the most renowned fashion brands, the company cultural heritage is thus a fundamental part of what marketing defines as "product concept", that is the totality of the tangible and intangible contributions, where the latter contemplate direct values such as the immediate conferral of status linked to the asset, but also indirect values that the company is able to communicate to the consumer through brand policy. The value of historical heritage constitutes for the fashion companies an emotional bond with its customers as through experience and tradition the quality of the product, its value and its positioning in historical key are recognized. The paper then analyzes the progress that has been made in Italy in recent years, for increase the value of business assets, starting from the heritage of the so-called industrial archeology, to arrive at that of companies specifically linked to fashion, foundations and museums of fashion. A reflection is also dedicated to the link that cultural institutions linked to business assets have with the territory and its enhancement