Search

Total knee arthroplasty (TKA) is a widely accepted and successful procedure for end-stage arthritis. Nevertheless, fast-track may be compromised by many factors, such as pain, edema, and blood loss. Cryotherapy has been advocated as a safe and effective strategy to improve the postoperative results, acting on pain, edema, and blood loss. This study is a prospective randomized controlled study, involving 50 patients after primary TKA. A power analysis was performed preoperatively. Twenty-four patients were addressed to a postoperative treatment with a continuous cold flow device (Hilotherm, Hilotherm GmbH, Germany). Twenty-six patients represented the control group, treated with crushed ice packs. All the patients shared the same analgesic strategy and the same rehabilitation protocol. Pain, analgesic consumption, active knee range of motion, drain output, transfusion requirement, and total blood loss were evaluated at different follow-ups (postoperative first, third, and seventh days). The two groups were homogenous for preoperative and intraoperative features. The groups showed no statistically significant differences in all the evaluated parameters. A modest reduction of knee volume was evident after 7 days from surgery (trend). No differences in blood loss were noticed. Continuous cold flow device in the acute postoperative setting after TKA did not show superiority in reducing edema, pain, and blood loss, compared with traditional icing regimen. Thus, due to the costs, it should be reserved to selected cases.

Direct vertebral rotation (DVR) is widely used to correct the axial deformity in adolescent idiopathic scoliosis (AIS). Indirect rotation techniques may help DVR in order to improve outcome. Vertebral translation technique combined with the use of two differently shaped rods resulted effective in reducing the rib hump deformity. The aim of this study is to describe the technique and evaluate the efficacy of combined DVR and vertebral translation technique on axial deformity correction. Mean follow-up was 2.7 years. Cobb angle, kyphosis angle, apical vertebrae axial rotation angle, SRS-22 questionnaire of 30 AIS patients treated with combined DVR and differently shaped dual rods translation technique were collected and compared preoperatively and postoperatively. At the last follow-up no screw pull-out, nonunion or loss of correction were recorded. The combination of DVR and differently shaped dual rods translation technique in AIS can provide good three-dimensional correction and improvement of patient’s quality of life.

A limiting factor for the long-term reliability of power MOSFET-based devices is the electro-thermal and/or thermo-mechanical aging of the metallic parts. In this paper we assess the bonding wire and source metallization degradation of power devices, designed for applications in the automotive industry. Our approach consists in characterizing the metal microstructure before and after accelerated aging tests, by scanning electron microscopy, ion milling and microscopy, focused ion beam tomography, transmission electron microscopy and grain structure mapping. To focus on the wire-metallization bonding interface, we have set up a dedicated sample preparation that allows us to disclose the metallization under the bonding wires. This critical location is significantly different from the naked metallization, as the bonding process induces plastic deformation prior to aging. The main mechanism behind the device failure is the generation and propagation of fatigue cracks in the aluminum metallization. Away and under the wire bonds, they run perpendicularly from the surface down to the silicon substrate following the grain boundaries, due to an enhanced self-diffusion of aluminum atoms. Moreover, initial imperfections in the wire-metallization bonding (small cavities and aluminum oxide residues) are the starting point for harmful cracks that propagate along the wire-metallization interface and can eventually cause the wire lift-off. These phenomena can explain the local increase in the device resistance occurring at failure.

Background: Severe posttraumatic ankle arthritis poses a reconstructive challenge in the young and active patient. Bipolar fresh total osteochondral allograft (BFTOA) may represent an intriguing alternative to arthrodesis and prosthetic replacement. The purpose of this article was to evaluate the outcomes of BFTOA performed through an anterior approach to the ankle and to investigate the parameters influencing the results. Methods: A total of 26 patients (18 males and 8 females with a mean age of 34.9 ± 7.7 years) underwent BFTOA. The allograft was prepared with the help of specifically designed jigs and the surgery was performed using a direct anterior approach. Patients were evaluated clinically and radiographically at 2, 4, 6, and 12 months after the operation, and at a mean 40.9 ± 14.1 months of follow-up. Radiographic evaluation included the measurement of allograft size matching and alignment. Results: The AOFAS score improved from 26.6 ± 6 preoperatively to 77.8 ± 8.7 after a mean follow-up of 40.9 ± 14.1 months ( P < .0005). Six failures occurred. Joint degeneration was classified as 2 in 12 and as 3 in 14 patients. A statistically significant correlation between low degrees of distal tibial slope and better clinical outcomes was observed ( P = .049). Conclusion: BFTOA appears to be a viable option to arthrodesis or arthroplasty. Precise allograft sizing, stable fitting, and fixation and delayed weight-bearing were key factors for a successful outcome. In this series the correct alignment of the tibial graft, in terms of slope, was found to play a crucial role in the allograft survivorship. Level of Evidence: Level IV, case series.

Introduction ankle sprains are a common sports-related injury. A 20% of acute ankle sprains results in chronic ankle instability, requiring surgery. Aim of this paper is to report the results of a series of 38 patients treated for chronic lateral ankle instability with anatomic reconstruction. Materials and methods thirty-eight patients were enrolled in the study. Seventeen patients underwent a surgical repair using the Brostrom-modified technique, while the remaining underwent anatomic reconstruction with autologous or allogenic graft. Results at a mean follow-up of 5 years the AOFAS score improved from 66.1 ± 5.3 to 92.2 ± 5.6. Discussion the findings of this study confirm that anatomic reconstruction is an effective procedure with satisfactory subjective and objective results which persist at long-term follow-up along with a low complication rate. No differences, in term of clinical and functional outcomes, were observed between the Brostrom-modified repair and the anatomic reconstruction technique. Level of evidence level IV.

A Th1 immune-preponderance has been shown in the immunopathogenesis of autoimmune thyroiditis (AT), Graves' disease (GD) and Graves’ Ophthalmopathy (GO), in which the Th1-chemokines (CXCL9, CXCL10, CXCL11), and their (C-X-C)R3 receptor, have a crucial role. Methimazole, and corticosteroids have been shown to modulate these chemokines; several efforts have been done to modulate the autoimmune reaction with other drugs, i.e. PPAR-γ, or -α ligands, or antibodies, or small molecules directed against CXCL10, or CXCR3. Antigen-specific therapy for GD, by inducing T cell tolerance through an immunization with TSH-R peptides, has been published. Drugs targeting cytokines [anti-TNFα (Etanercept), and anti-IL-6 (Tocilizumab)], and RTX (a chimeric monoclonal antibody vs. CD20) have been used in GO, with promising results. Teprotumumab (a human monoclonal anti-IGF-1R blocking antibody) has been investigated in a trial, showing it was very effective in GO patients. Still, more studies are needed for new therapies targeting autoimmune thyroid disorders.

Autoimmune thyroid diseases (AITD) are organ-specific autoimmune disorders mediated by Th1 lymphocytes, whose main clinical presentations are Hashimoto's thyroiditis (HT), or Graves' disease (GD). HT, GD, thyroid autoantibodies and thyroid dysfunctions have been shown in systemic rheumatologic diseases (as Sjögren's syndrome, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, or cryoglobulinemia). New associations of AITD with other autoimmune diseases are being discovered, for example with psoriatic arthritis and dermatological diseases. Several investigations suggest the importance of a shared genetic susceptibility and of environmental factors in patients with AITD and associated systemic autoimmunity. A major Th1 autoimmune response occurs in the initial, and/or active phases of organ-specific autoimmune disorders and/or systemic rheumatologic diseases with increased serum, or tissue, expressions of the Th1 chemokine CXCL10. Thyroid dysfunctions might have an important clinical impact, so a periodic thyroid screening in women with systemic or dermatological autoimmunity, overall in presence of thyroid autoantibodies is suggested.

The antitumor activity of vandetanib [a multiple signal transduction inhibitor including the RET tyrosine kinase, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor (VEGFR), ERK and with antiangiogenic activity], in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C [undifferentiated thyroid cancer (TC)] and in an ATC‑cell line (AF), was investigated in the present study. Vandetanib (1 and 100 nM; 1, 10, 25 and 50 µM) was tested by WST‑1, apoptosis, migration and invasion assays: in primary ATC cells, in the 8305C continuous cell line, and in AF cells; and in 8305C cells in CD nu/nu mice. Vandetanib significantly reduced ATC cell proliferation (P

The Armenian prince Ašot II Bagratuni (685/686-688/689 d.C.) placed in the church he himself founded in the village of Daroynkʽ a Byzantine icon mentioned in the Armenian historical sources as an image of the «Incarnation of Christ», coming from «the West». The years of the principate of Ašot partly coincide with those of the first of the two reigns of Justinian II, the emperor who for the first time issued monetary coins with the image of Christ impressed, and presided in 692 d.C. the Quinisext Council ‘in Trullo’, whose canon no. LXXXII dealt with the representation of the Saviour’s body. The case of Ašot is an example of the worship of icons in the late 7th century Armenia, and contributes to witnes both the circulation of this kind of artifacts in the armenian territories, and the the impact of the contemporary reflections about the Incarnation of Christ and the sacred images; in agreement, moreover, with the condemnation of the iconoclastic theses expressed in the Armenian treatise attributed to Vrtʽanēs Kʽertʽoł.

Questo nuovo volume della serie Eurasiatica. Quaderni di Studi su Balcani, Anatolia, Iran, Caucaso e Asia Centrale delle Edizioni Ca’ Foscari di Venezia raccoglie diversi articoli dedicati all’Armenia, al Caucaso e all’Asia Centrale. Gli articoli del volume vanno dall’archeologia alla letteratura, dal folclore alla storia, dalla storia del cristianesimo orientale all’arte, dalla narrazione di viaggio all’urbanistica. Un’intera sezione è dedicata agli studi osseti, di grande interesse non solo nell’ambito caucasico e in quello iranistico, ma anche per quel che riguarda la storia e la cultura russe.

Questo nuovo volume della serie Eurasiatica. Quaderni di Studi su Balcani, Anatolia, Iran, Caucaso e Asia Centrale delle Edizioni Ca’ Foscari di Venezia raccoglie diversi articoli dedicati all’Armenia, al Caucaso e all’Asia Centrale. Gli articoli del volume vanno dall’archeologia alla letteratura, dal folclore alla storia, dalla storia del cristianesimo orientale all’arte, dalla narrazione di viaggio all’urbanistica. Un’intera sezione è dedicata agli studi osseti, di grande interesse non solo nell’ambito caucasico e in quello iranistico, ma anche per quel che riguarda la storia e la cultura russe.

Background and objective Lenvatinib is an oral, multitargeted Tyrosine Kinase Inhibitor (TKI) of Vascular Endothelial Growth Factor Receptors (VEGFR1-VEGFR3), fibroblast growth factor receptors (FGFR1-FGFR4), Platelet-Derived Growth Factor Receptor (PDGFR)α, rearranged during transfection (RET), and v-kit (KIT) signaling networks implicated in tumor angiogenesis. Method Here, we review the scientific literature about lenvatinib in the treatment of thyroid cancer. Results In vitro studies have shown antineoplastic activity of lenvatinib in Differentiated Thyroid Cancer (DTC), mainly because of its antiangiogenetic effects, but a slight effect on thyroid cancer cell proliferation has been shown. In vivo Phase II, and Phase III studies in patients with aggressive DTC not responsive to radioiodine, have shown that lenvatinib administration was associated with an amelioration in Progression-Free Survival (PFS) with respect to placebo (median PFS 18.2 vs. 3.6 months). However, overall survival was not significantly changed. Lenvatinib is also effective in patients resistant to sorafenib as salvage therapy. Adverse effects of any grade occur in more than 40% of lenvatinib-treated patients, mainly hypertension, diarrhea, asthenia or fatigue, nausea, decreased appetite, and decreased weight. Discontinuations of the therapy because of adverse effects occur in about 14% of patients. Moreover, deaths considered to be drug-related can occur. Conclusion On the basis of the above-mentioned considerations, it is necessary to prove the effectiveness of lenvatinib in the context of associated moderate to severe toxicities requiring frequent dose reduction and delays, and for this reason, many interesting patents have been recently applied.

The expression ‘chiese di cristallo’ (crystal churches) appeared in the title of an article written by Cesare Brandi in 1968 for the Italian newspaper Corriere della Sera, which reviewed a photo exhibition on Armenian architecture. This definition for Armenian churches met some success in critical studies and it is often used in non-academic literature. The aim of this brief essay is to explain Brandi’s metaphor of crystal in light of earlier theoretical considerations – such as the ones of Alois Riegl and Wilhelm Worringer – and in relation to additional examples of this expression found in Italian art critics of the first half the 20th century., Venezia Arti

The Armenian prince Ašot II Bagratuni (685/686-688/689 d.C.) placed in the church he himself founded in the village of Daroynkʽ a Byzantine icon mentioned in the Armenian historical sources as an image of the «Incarnation of Christ», coming from «the West». The years of the principate of Ašot partly coincide with those of the first of the two reigns of Justinian II, the emperor who for the first time issued monetary coins with the image of Christ impressed, and presided in 692 d.C. the Quinisext Council ‘in Trullo’, whose canon no. LXXXII dealt with the representation of the Saviour’s body. The case of Ašot is an example of the worship of icons in the late 7th century Armenia, and contributes to witnes both the circulation of this kind of artifacts in the armenian territories, and the the impact of the contemporary reflections about the Incarnation of Christ and the sacred images; in agreement, moreover, with the condemnation of the iconoclastic theses expressed in the Armenian treatise attributed to Vrtʽanēs Kʽertʽoł., Eurasiatica

Background: Demoralization syndrome is a significant condition that has not been greatly studied in Southern European countries. Aims: To extend the knowledge of demoralization in Southern Europe by examining its prevalence according to different methods of assessment, its relationship with anxiety and depression, and its impact on quality of life (QoL) among cancer patients. Methods: A convenience sample of 195 cancer outpatients from two oncology centers (102 from Lisbon, Portugal, and 93 from Ferrara, Italy) participated in an observational, cross-sectional study using the Diagnostic Criteria of Psychosomatic Research-Demoralization interview (DCPR/D) and psychometric tools (Demoralization scale-DS; Patient Health Questionnaire-9/PHQ-9; Hospital Anxiety Depression Scale-HADS; and European Quality of Life-5-EQ-5D). Results: A 25.1% prevalence (CI 95%, 0.19-0.31) of clinically relevant demoralization was reported on the DCPR/D interview. A total demoralization score cutoff score ≥ 25 maximized sensitivity (81.6%), and specificity (72.6%) in identifying DCPR/D demoralized patients. The DCPR/D and DS were associated with poorer levels of QoL. About half of the patients who were demoralized were not clinically depressed (PHQ-9). Self-reported suicidal ideation (PHQ-9 item 9) was found in a minority of patients (8.2%), most of whom (77%) were cases of depression (PHQ-9), but one-quarter (23%) were not depressed, yet moderately/severely demoralized (DCPR/D and DS). Conclusions: This Southern European study confirms the importance of demoralization in cancer patients as a different condition with respect to depression and its relationship with poor QoL and suicidal ideation. info:eu-repo/semantics/publishedVersion

Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor (TKI) of VEGFR1-VEGFR3, FGFR1-FGFR4, PDGFRα, RET and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) signaling networks involved in tumor angiogenesis. We have evaluated the antitumor activity of lenvatinib in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C (undifferentiated thyroid cancer) and in an ATC-cell line (AF). The AF cell line was obtained from the primary ATC cultures and was the one that grew over 50 passages. The effect of lenvatinib (1 and 100 nM; and 1, 10, 25 and 50 µM) was investigated in primary ATC, 8305C and AF cells as well as in AF cells in CD nu/nu mice. Lenvatinib significantly reduced ATC cell proliferation (P

This thesis, a collaboration between CEMES-CNRS, Satie laboratory (ENS Cachan) and NXP Semiconductors is motivated by the comprehension of the failure mechanisms of low voltage power MOSFET devices produced for ap- plications in the automotive industry. A limiting factor for the long-term reliability of power modules is the electro- thermal and/or thermo-mechanical aging of the metallic parts of the source: Al metallization and bonding wires. At the temperature reached during the on-off operating cycles (few hundred degrees), the difference in the coefficient of thermal expansion between the metallization and the oxide and semicon- ductor parts induces an inevitable plastic deformation in the metal, which is the softest material in the complex MOSFET architecture. We have characterized the metal microstructure before and after accelerated electro-thermal aging tests, by using specific techniques from the field of the physical metallurgy: electron and ion microscopy, grain orientation and chem- ical composition mapping. For the first time the source metallization has been characterized both away and under the bonding connections, which are one hundred times thicker than the metallization layer. The latter is a critical loca- tion for the reliability assessment because the ultrasonic bonding process may weaken the initial metallization microstructure by adding an important plas- tic deformation prior to aging. This is, however, poorly stated in the literature because of the difficulty to access the metallization under the wires without damaging their bonding, which is known to be particularly weak in case of aged modules. In order to investigate the wire-metallization interface, we have set up origi- nal sample preparations, based on ion polishing, that allowed us to disclose the metallization under the bonding wires without introducing preparation artifacts in the microstructure. The bonding process induces a severe and non- uniform plastic deformation in the metallization under the wires without re- creating a good electrical contact: small cavities and native oxide residues, have been systematically observed at the Al/Al interface, in all the analyzed mod- ules, before and after aging. The main mechanism behind the device failure is the generation and propa- gation of fatigue cracks in the aluminum metallization, associated to a local Al oxidation that prevents these crack from closing. Away and under the wire bonds, they run perpendicularly from the surface down to the silicon substrate following the grain boundaries, due to an enhanced intergranular diffusion of aluminum atoms. In the bonding area, the phenomenon of parallel cracking is favored by the initial imperfections in the wire-metallization bonding. Ion to- mography experiments have shown that these cracks are confined to the wire- metal interface and do not propagate in the wire despite its lower strength (pure Al, larger grain structure). Crack propagation along the Al/Al interface can cause a contact reduction between the wire and the source metallization and eventually its failure. Such discontinuities in the metal can explain the lo- cal increase in the device resistance and temperature that accelerates the aging process until failure. This study settled new, dedicated techniques and quantification methods to as- sess the aging of the metal parts of MOSFET devices. The full characterization of the intrinsically defective interface generated by the bonding process and the metallization degradation during electro-thermal aging indicated paths to possible improvements of current technologies and potential developments of new processes.; Cette thèse, effectuée en collaboration entre le CEMES-CNRS, le laboratoire Satie (ENS Cachan) et NXP Semiconductors est motivée par la compréhension des mécanismes de défaillance des dispositifs MOSFET pour les applications dans l'industrie automobile. Un facteur limitant de la fiabilité à long terme des modules de puissance basse tension est le vieillissement électrothermique et/ou thermo-mécanique des parties métalliques de la source: métallisation en aluminium (ou alliage) et fils de connexion. A cause de la différence de coefficient de dilatation thermique entre la métallisation les oxydes et le substrat semi-conducteur, la température atteinte pendant les cycles de fonctionnement (quelques centaines de degrés), induit une déformation plastique inévitable dans le métal, qui est le matériau le plus mou dans l'architecture complexe du MOSFET. Nous avons caractérisé la microstructure métallique avant et après les tests de vieillissement électrothermique accélérés, en utilisant des techniques spécifiques du domaine de la métallurgie physique: microscopie électronique et ionique, cartographie d'orientation de grains et de la composition chimique. Pour la première fois, la métallisation de la source a été caractérisée sous les fils de connexion, qui sont cent fois plus épais que la métallisation. Cet emplacement est critique pour la fiabilité du composant, car le processus de soudure par ultrasons induit une déformation plastique importante qui peut affaiblir la métallisation initiale avant le vieillissement. Ceci est peu étudié dans la littérature en raison de la difficulté à accéder à la métallisation sous les fils sans altérer leur interface, souvent endommagée et fragilisée dans les modules vieillis. Nous avons mis en place des méthodes de préparation d'échantillon, basées sur le polissage ionique, pour étudier cette interface, sans introduire d'artefacts de préparation. Le processus de soudure à froid induit une déformation plastique sévère et non uniforme dans la métallisation sous les fils sans parvenir à recréer un bon contact électrique: de petites cavités et des résidus d'oxyde natif, ont été systématiquement observés à l'interface Al / Al, dans tous les modules analysés, avant et après vieillissement. Le mécanisme principal de défaillance des modules est la génération et la propagation de fissures de fatigue dans l'aluminium, associée à une oxydation locale qui empêche la fermeture de ces fissures. Sous et en dehors des fils de connexion, ces fissures traversent la métallisation perpendiculairement à la surface jusqu'au substrat en silicium en suivant les joints de grains. Cette fissuration est due à la diffusion intergranulaire accélérée des atomes d'aluminium. Dans la zone de soudure, le phénomène de fissuration parallèle à l'interface est favorisé par les imperfections initiales (cavités, oxyde). Les expériences de tomographie ionique ont montré que ces fissures sont confinées à l'interface fil-métal et ne se propagent pas dans le fil malgré sa plus faible résistance mécanique (Al pur, structure à grains plus grands). La propagation de la fissure le long de l'interface Al/Al peut provoquer une diminution du contact entre le fil et la métallisation de la source et éventuellement son décollement. Les fissures dans le métal source peuvent expliquer l'augmentation locale de la résistance et de la température du module qui accélère le processus de vieillissement jusqu'à l'échec. Cette étude a établi de nouvelles techniques dédiées et des méthodes de quantification pour évaluer le vieillissement des parties métalliques des modules MOSFET. La caractérisation complète de l'interface soudée, intrinsèquement défectueuse et la dégradation de la métallisation pendant le vieillissement électrothermique ouvrent la voie à l'amélioration possible les technologies actuelles et au développement potentiel de nouveaux procédés.

Tyrosine kinase inhibitors (TKIs) are molecules that compete with ATP on tyrosine kinase receptors (TKRs), blocking tyrosine kinase (TK) activation and then oncogenic pathways; they have been studied, and some of them are right approved for the treatment of many types of cancer. Among TKIs, one of the most explored chemical template is the pyrazolo[3,4-d]pyrimidine (PP) heterocyclic core, which proved to be a useful scaffold for the obtainment of effective compounds. Actually, derivatives belonging to this structural class show a large spectrum of activity, thus standing out as multi-target agents. Different PP compounds have been shown to act as: a) ABL inhibitors and antiproliferative agents against human leukemia cell lines; b) Src kinase inhibitors in neuroblastoma, medulloblastoma and osteosarcoma; c) Phospholipase D inhibitors in different neoplasias; d) Urokinase plasminogen activator inhibitors, in breast cancer. In thyroid cancer (TC), PP1 and PP2 (inhibitors of RET, Hck, lck, and fynT kinases, and a good inhibitor of c-Src and platelet-derived growth factor receptor) showed antineoplastic actvity in human papillary TC cell lines that carry spontaneous RET/PTC1 rearrangements. More recently, new derivatives, (R)-1-phenethyl-N-(1-phenylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4- amine, namely, CLM3 and CLM29, have been demonstrated to exert a multiple signal transduction inhibition (including the RET-TK, BRAF, EGFR, and with antiangiogenic activity), showing antineoplastic activity, in vitro and in vivo, in papillary dedifferentiated, medullary and anaplastic TC. These data have shown the antineoplastic activity of PP in different neoplasias, opening the way to a future clinical evaluation in human cancers.

We report the development of magnetic nanocomposite sheets with superhydrophobic and supeoleophilic surfaces generated by laser ablation. Polydimethylsiloxane elastomer free-standing films, loaded homogeneously with 2% wt. carbon coated iron nanoparticles, were ablated by UV (248 nm), nanosecond laser pulses. The laser irradiation induces chemical and structural changes (both in micro- and nano-scale) to the surfaces of the nanocomposites rendering them superhydrophobic. The use of nanoparticles increases the UV light absorption efficiency of the nanocomposite samples, and thus facilitates the ablation process, since the number of pulses and the laser fluence required are greatly reduced compared to the bare polymer. Additionally the magnetic nanoparticles enhance significantly the superhydrophobic and oleophilic properties of the PDMS sheets, and provide to PDMS magnetic properties making possible its actuation by a weak external magnetic field. These nanocomposite elastomers can be considered for applications requiring magnetic MEMS for the controlled separation of liquids.