Ankle Bipolar Fresh Osteochondral Allograft Survivorship and Integration: Transplanted Tissue Genetic Typing and Phenotypic Characteristics

Il trapianto fresco bipolare o allograft di caviglia puo rappresentare una valida alternative nel trattamento dell’artrosi post-traumatica nel paziente giovane ed attivo. Nonostante l’utilizzo di tale procedura, poco si conosce sulla ricolonizzazione del trapianto osteocondrale da parte delle cellule del ricevente. Scopo di questo studio era definire il profilo genotipico di prelievi bioptici eseguiti da allograft di caviglia a 21 mesi di follow-up. 22 allograft sono stati inclusi nello studio. Lo score clinico AOFAS e la valutazione radiologica è stata eseguita al follow-up finale di 61±13.6 mesi. 22 prelievi bioptici sono stati prelevati ad una media di 21 mesi di FU. Sono stati analizzati con valutazione istologica ed immunoistochimica. 20 prelievi sono stati confrontati mediante typing genetico con il DNA del donatore e del ricevente. In 6 casi è stata associata una valutazione fenotipica della popolazione cellulare rinvenuta nel prelievo bioptico con valutazione dell’espressione genica. Abbiamo osservato 2 fallimenti. Lo score AOFAS è passato da un valore pre-operatorio di 25,7 ± 8.0 punti a 76.2±14.1 (p<0.05) al follow up finale. L’analisi genotipica ha mostrato una popolazione compatibile con il ricevente in 12 casi, una popolazione mista ricevente donatore in 5 e la presenza esclusiva di cellule del donatore in 3. L’analisi dell’espressione genica ha evidenziato markers specifici della linea cartilaginea. L’analisi genotipica e le valutazioni istologiche ed immunoistochimiche suggeriscono una migrazione di cellule del ricevente nella porzione cartilaginea dell’allograft a partenza dall’osso subcondrale. L’analisi dell’espressione genica sembra suggerire che queste cellule, una volta migrate, possano differenziarsi nella linea cartilaginea.Ankle bipolar fresh osteochondral allograft may represent a valid alternative in the treatment of sever post-traumatic ankle arthritis in young and active patients. Despite the widespread use of this procedure little is known about allograft recolonization by host cells. Aim of this study was to assess the genotypic profile and the phenotypic pattern of retrieved specimens from ankle allografts at 21 months follow-up. 22 ankle allografts were included in the study. AOFAS clinical score and radiographic evaluation was performed up to the final follow-up of 61±13.6 months. 22 bioptic specimens harvested at 21 months follow-up were analyzed by histological and immunohistochemical analysis. 20 specimens were compared with recipient and donor constitutional DNA by genotyping. In 6 cases gene expression was evaluated by means of real-time reverse transcription-polymerase chain reaction. We observed 2 failures. AOFAS score improved from 25,7 ± 8.0 points pre-operatively to 77,5 ±11,2 at 12 months follow-up and 76.2±14.1 (p<0.05) at final follow-up. Genotyping on allograft retrieved specimens showed an exclusive recipient cellular population in 12 cases, a mixed profile in 5 cases and exclusive presence of donor cells in 3 cases. Gene expression analysis showed that grafted cartilage expressed cartilage-specific markers. The genotyping analysis along with histological and immunohistochemical evaluations suggest the ingrowth of host cells into the transplanted cartilage migrating from the subchondral bone and crossing the tidemark. Gene expression analysis seems to suggest that these cells, once migrated, may differentiate toward cartilaginous lineage

Characterization of Er in porous Si

The fabrication of porous Si-based Er-doped light emitting devices is a very promising developing field for all-silicon light emitters. However, while luminescence of Er-doped porous silicon devices has been demonstrated, very little attention has been devoted to the doping process itself. We have undertaken a detailed study of this process examining the porous silicon matrix from several points of view, during and after the doping. In particular, we have found that the Er doping process shows a threshold level which, as evidenced by the cross correlation of the various techniques used, does depend on the sample thickness and on the doping parameters

Operational research and the Royal Canadian Air Force Eastern Air Command\u27s search for efficiency in airborne anti-submarine warfare, 1942-1945

This thesis analyses the contributions of operational research to the work of the Royal Canadian Air Force Eastern Air Command during the Second World War. The efforts of the handful of Canadian operational researchers in the Allied campaign against the German U-boat force, although having produced only modest results, did make a small but important contribution to the war which have been neglected by historians. The use of aircraft against submarines began during the First World War when both technologies were still in their infancy. Although initial results were poor, the handful of sinkings by aircraft demonstrated its potential as a counter to the seemingly invulnerable submarine. Great Britain, with its vulnerable seaward lines of communication, emerged by 1918 as the leader in the development of anti-submarine aircraft, largely through the co-operative efforts of scientists and airmen to refine and advance the concept of airborne anti-submarine warfare. Although much of this knowledge was squandered through the neglect of the Royal Air Force’s land-based anti-submarine aircraft force during the inter-war period, the early introduction of scientists to the field of airborne anti-submarine warfare provided a precedent for a future revival of this relationship. The techniques of operational research, first promulgated during the British experiments with radar during the 1930s, were, by 1941, applied to assist Royal Air Force Coastal Command in its campaign against the German U-boats which were taking an ever-increasing toll of Allied shipping. The work of P.M.S. Blackett and his staff at Coastal Command Operational Research Section would serve as the foundation upon which Eastern Air Command’s Operational Research Section (ORS) would be constructed when it was created in November 1942. Under the leadership of Professor Colin Barnes and later Dr. J.W.T. Spinks, Eastern Air Command ORS produced a series of studies which explored issues of concern to the Command’s anti-submarine (bomber-reconnaissance) squadrons. They used methodologies adapted for Canadian purposes from the original British and American models. These studies of diverse topics such as bombing accuracy and search techniques for missing aircraft, along with the squadron and Command efficiency data collected in operational planning role assumed by Eastern Air Command ORS (one which had earlier been rejected as unproductive clerical work by Coastal Command ORS), characterized the growth of Canadian-oriented operational research during the final three years of the Second World War. The work of the handful of civilian and military operational researchers at Eastern Air Command ORS, although threatened with elimination during the deep cuts to the military in the immediate post-war years, survived to form part of the body of Canadian military operational research techniques which has assisted the Canadian Forces in their duties throughout the last half-century

Cámara oscura

Poema traducido del Italiano por Guillermo Fernández y publicado en la revista "La Colmena" No. 46 del año 2006, de la Universidad Autónoma del Estado de México, en la sección "Italia en la Colmena"

Controlling the Er content of porous silicon using the doping current intensity

The results of an investigation on the Er doping of porous silicon are presented. Electrochemical impedance spectroscopy, optical reflectivity, and spatially resolved energy dispersive spectroscopy (EDS) coupled to scanning electron microscopy measurements were used to investigate on the transient during the first stages of constant current Er doping. Depending on the applied current intensity, the voltage transient displays two very different behaviors, signature of two different chemical processes. The measurements show that, for equal transferred charge and identical porous silicon (PSi) layers, the applied current intensity also influences the final Er content. An interpretative model is proposed in order to describe the two distinct chemical processes. The results can be useful for a better control over the doping process

Cytokines and HCV-related autoimmune disorders

Cytokines are intercellular mediators involved in viral control and liver damage being induced by infection with hepatitis C virus (HCV). The complex cytokine network operating during initial infection allows a coordinated, effective development of both innate and adaptive immune responses. However, HCV interferes with cytokines at various levels and escapes immune response by inducing a T-helper (Th)2/T cytotoxic 2 cytokine profile. Inability to control infection leads to the recruitment of inflammatory infiltrates into the liver parenchyma by interferon (IFN)-γ-inducible CXC chemokine ligand (CXCL)9, -10, and -11 chemokines, which results in sustained liver damage and eventually in liver cirrhosis. The most important systemic HCV-related extrahepatic diseases-mixed cryoglobulinemia, lymphoproliferative disorders, thyroid autoimmune disorders, and type 2 diabetes-are associated with a complex dysregulation of the cytokine/chemokine network, involving proinflammatory and Th1 chemokines. The therapeutical administration of cytokines such as IFN-α may result in viral clearance during persistent infection and revert this process. Theoretically agents that selectively neutralize CXCL10 could increase patient responsiveness to traditional IFN-based HCV therapy. Several studies have reported IL-28B polymorphisms and circulating CXCL10 may be a prognostic markers for HCV treatment efficacy in HCV genotype 1 infection

CLM3 e Carcinoma Anaplastico della Tiroide

Il carcinoma anaplastico della tiroide (ATC) è una delle forme tumorali più aggressive e letali, che quasi inevitabilmente in tempi brevi conduce alla morte i pazienti affetti. Nonostante siano state testate varie modalità di trattamento, tra cui la combinazione dell’intervento chirurgico con la radioterapia e/o la chemioterapia, la prognosi di questi pazienti non risulta sostanzialmente modificata. Sono state, quindi, proposte nuove strategie di trattamento, tra cui l’utilizzo di nuovi agenti farmacologici, in particolare le molecole inibitrici delle tirosin-chinasi (TKI). I TKI risultano avere un ruolo importante nel trattamento dell’oncogenesi e dell’angiogenesi patologica, in quanto determinano l’inibizione della trasmissione del segnale mitogeno attraverso il fattore di crescita vascolare endoteliale (VEGFR) e il recettore del fattore di crescita epidermico (EGFR), impedendo la fosforilazione dei residui di tirosina associati al recettore. Con questa tesi è stata studiata l’attività antineoplastica e antiangiogenica di un composto pirazolopirimidinico (CLM3) con la capacità di inibire multiple vie di trasduzione del segnale (includendo la tirosin-chinasi RET, EGFR e VEGF) in colture cellulari primarie di ATC, nella linea cellulare umana 8305C (carcinoma indifferenziato della tiroide) e in una linea cellulare di ATC (AF), ottenuta spontaneamente in coltura. CLM3 è stato testato sulle cellule primarie di ATC alle concentrazioni di 5, 10, 30, e 50 μM; nelle cellule 8305C e nella linea AF sono state utilizzate le concentrazioni 1, 5, 10, 30, 50, or 100 μM. CLM3 è stato, inoltre, testato in vivo nei topi CD nu/nu con la linea AF. CLM3 ha inibito significativamente la proliferazione cellulare nelle linee 8305C e AF, inducendo anche l’apoptosi. Si è osservata una significativa riduzione della proliferazione anche nelle cellule ATC (p < 0.01). CLM3 aumentava la percentuale di apoptosi nelle cellule di ATC in maniera dose dipendente (p < 0.001), inibiva la migrazione (p < 0.01) e l’invasione (p < 0.001). La linea cellulare AF è stata iniettata a livello sottocutaneo in topi CD nu/nu e ha portato allo sviluppo di una massa tumorale identificabile nei successivi 15 giorni. CLM3 (50 mg/Kg/die) ha inibito significativamente la crescita tumorale partendo dal sedicesimo giorno dopo l’inizio del trattamento. CLM3 riduceva significativamente l’espressione di VEGF-A e la densità microvascolare del tessuto tumorale AF. CLM3 inibiva, inoltre, la fosforilazione di EGFR, AKT ed ERK1/2 e deregolava la ciclina D1 nelle 8305C e nella linea AF. In conclusione, l’attività antitumorale e antiangiogenica di CLM3, composto pirazolopirimidinico, risulta essere interessante e molto promettente nel trattamento dell’ATC, aprendo la strada alla futura valutazione clinica

Reversible normalisation of serum TSH levels in patients with autoimmune atrophic gastritis who received L-T4 in tablet form after switching to an oral liquid formulation: A case series

Background: L-thyroxine (L-T4) malabsorption is a potential concern in patients with autoimmune atrophic gastritis. Methods: We evaluated five patients with autoimmune gastritis, who showed high serum thyrotropin (TSH) levels (in the hypothyroid range) while in therapy with L-T4 in tablet. All patients were switched to receive an oral L-T4 liquid formulation maintaining the same dosage. Results: In all patients who received L-T4 in tablet form after switching to an oral liquid formulation with the same L-T4 dosage, TSH circulating levels were normalized. In four patients who were switched back again to receive L-T4 in tablets, maintaining the dosage, TSH levels worsened again reaching levels in the hypothyroid range. Conclusions: The fact that the change from tablets to liquid oral formulation normalised serum TSH levels, and that switching back to tablets caused thyrotropin levels to worsen, leads us to believe that absorption of L-T4 is greater with oral liquid formulations in these patients. These results suggest that the L-T4 oral liquid formulation could circumvent the pH alteration resulting from atrophic gastritis