Neural basis of visual deficits recovery: visual residual functions and multisensory integration.

The ability of integrating into a unified percept sensory inputs deriving from different sensory modalities, but related to the same external event, is called multisensory integration and might represent an efficient mechanism of sensory compensation when a sensory modality is damaged by a cortical lesion. This hypothesis has been discussed in the present dissertation. Experiment 1 explored the role of superior colliculus (SC) in multisensory integration, testing patients with collicular lesions, patients with subcortical lesions not involving the SC and healthy control subjects in a multisensory task. The results revealed that patients with collicular lesions, paralleling the evidence of animal studies, demonstrated a loss of multisensory enhancement, in contrast with control subjects, providing the first lesional evidence in humans of the essential role of SC in mediating audio-visual integration. Experiment 2 investigated the role of cortex in mediating multisensory integrative effects, inducing virtual lesions by inhibitory theta-burst stimulation on temporo-parietal cortex, occipital cortex and posterior parietal cortex, demonstrating that only temporo-parietal cortex was causally involved in modulating the integration of audio-visual stimuli at the same spatial location. Given the involvement of the retino-colliculo-extrastriate pathway in mediating audio-visual integration, the functional sparing of this circuit in hemianopic patients is extremely relevant in the perspective of a multisensory-based approach to the recovery of unisensory defects. Experiment 3 demonstrated the spared functional activity of this circuit in a group of hemianopic patients, revealing the presence of implicit recognition of the fearful content of unseen visual stimuli (i.e. affective blindsight), an ability mediated by the retino-colliculo-extrastriate pathway and its connections with amygdala. Finally, Experiment 4 provided evidence that a systematic audio-visual stimulation is effective in inducing long-lasting clinical improvements in patients with visual field defect and revealed that the activity of the spared retino-colliculo-extrastriate pathway is responsible of the observed clinical amelioration, as suggested by the greater improvement observed in patients with cortical lesions limited to the occipital cortex, compared to patients with lesions extending to other cortical areas, found in tasks high demanding in terms of spatial orienting. Overall, the present results indicated that multisensory integration is mediated by the retino-colliculo-extrastriate pathway and that a systematic audio-visual stimulation, activating this spared neural circuit, is able to affect orientation towards the blind field in hemianopic patients and, therefore, might constitute an effective and innovative approach for the rehabilitation of unisensory visual impairments.

Tactile perception - Perception of tactile distance changes with body site: a neural network modelling study.

La distorsione della percezione della distanza tra due stimoli puntuali applicati sulla superfice della pelle di diverse regioni corporee è conosciuta come Illusione di Weber. Questa illusione è stata osservata, e verificata, in molti esperimenti in cui ai soggetti era chiesto di giudicare la distanza tra due stimoli applicati sulla superficie della pelle di differenti parti corporee. Da tali esperimenti si è dedotto che una stessa distanza tra gli stimoli è giudicata differentemente per diverse regioni corporee. Il concetto secondo cui la distanza sulla pelle è spesso percepita in maniera alterata è ampiamente condiviso, ma i meccanismi neurali che manovrano questa illusione sono, allo stesso tempo, ancora ampiamente sconosciuti. In particolare, non è ancora chiaro come sia interpretata la distanza tra due stimoli puntuali simultanei, e quali aree celebrali siano coinvolte in questa elaborazione. L’illusione di Weber può essere spiegata, in parte, considerando la differenza in termini di densità meccano-recettoriale delle differenti regioni corporee, e l’immagine distorta del nostro corpo che risiede nella Corteccia Primaria Somato-Sensoriale (homunculus). Tuttavia, questi meccanismi sembrano non sufficienti a spiegare il fenomeno osservato: infatti, secondo i risultati derivanti da 100 anni di sperimentazioni, le distorsioni effettive nel giudizio delle distanze sono molto più piccole rispetto alle distorsioni che la Corteccia Primaria suggerisce. In altre parole, l’illusione osservata negli esperimenti tattili è molto più piccola rispetto all’effetto prodotto dalla differente densità recettoriale che affligge le diverse parti del corpo, o dall’estensione corticale. Ciò, ha portato a ipotizzare che la percezione della distanza tattile richieda la presenza di un’ulteriore area celebrale, e di ulteriori meccanismi che operino allo scopo di ridimensionare – almeno parzialmente – le informazioni derivanti dalla corteccia primaria, in modo da mantenere una certa costanza nella percezione della distanza tattile lungo la superfice corporea. E’ stata così proposta la presenza di una sorta di “processo di ridimensionamento”, chiamato “Rescaling Process” che opera per ridurre questa illusione verso una percezione più verosimile. Il verificarsi di questo processo è sostenuto da molti ricercatori in ambito neuro scientifico; in particolare, dal Dr. Matthew Longo, neuro scienziato del Department of Psychological Sciences (Birkbeck University of London), le cui ricerche sulla percezione della distanza tattile e sulla rappresentazione corporea sembrano confermare questa ipotesi. Tuttavia, i meccanismi neurali, e i circuiti che stanno alla base di questo potenziale “Rescaling Process” sono ancora ampiamente sconosciuti. Lo scopo di questa tesi è stato quello di chiarire la possibile organizzazione della rete, e i meccanismi neurali che scatenano l’illusione di Weber e il “Rescaling Process”, usando un modello di rete neurale. La maggior parte del lavoro è stata svolta nel Dipartimento di Scienze Psicologiche della Birkbeck University of London, sotto la supervisione del Dott. M. Longo, il quale ha contribuito principalmente all’interpretazione dei risultati del modello, dando suggerimenti sull’elaborazione dei risultati in modo da ottenere un’informazione più chiara; inoltre egli ha fornito utili direttive per la validazione dei risultati durante l’implementazione di test statistici. Per replicare l’illusione di Weber ed il “Rescaling Proess”, la rete neurale è stata organizzata con due strati principali di neuroni corrispondenti a due differenti aree funzionali corticali: • Primo strato di neuroni (il quale dà il via ad una prima elaborazione degli stimoli esterni): questo strato può essere pensato come parte della Corteccia Primaria Somato-Sensoriale affetta da Magnificazione Corticale (homunculus). • Secondo strato di neuroni (successiva elaborazione delle informazioni provenienti dal primo strato): questo strato può rappresentare un’Area Corticale più elevata coinvolta nell’implementazione del “Rescaling Process”. Le reti neurali sono state costruite includendo connessioni sinaptiche all’interno di ogni strato (Sinapsi Laterali), e connessioni sinaptiche tra i due strati neurali (Sinapsi Feed-Forward), assumendo inoltre che l’attività di ogni neurone dipenda dal suo input attraverso una relazione sigmoidale statica, cosi come da una dinamica del primo ordine. In particolare, usando la struttura appena descritta, sono state implementate due differenti reti neurali, per due differenti regioni corporee (per esempio, Mano e Braccio), caratterizzate da differente risoluzione tattile e differente Magnificazione Corticale, in modo da replicare l’Illusione di Weber ed il “Rescaling Process”. Questi modelli possono aiutare a comprendere il meccanismo dell’illusione di Weber e dare così una possibile spiegazione al “Rescaling Process”. Inoltre, le reti neurali implementate forniscono un valido contributo per la comprensione della strategia adottata dal cervello nell’interpretazione della distanza sulla superficie della pelle. Oltre allo scopo di comprensione, tali modelli potrebbero essere impiegati altresì per formulare predizioni che potranno poi essere verificate in seguito, in vivo, su soggetti reali attraverso esperimenti di percezione tattile. E’ importante sottolineare che i modelli implementati sono da considerarsi prettamente come modelli funzionali e non intendono replicare dettagli fisiologici ed anatomici. I principali risultati ottenuti tramite questi modelli sono la riproduzione del fenomeno della “Weber’s Illusion” per due differenti regioni corporee, Mano e Braccio, come riportato nei tanti articoli riguardanti le illusioni tattili (per esempio “The perception of distance and location for dual tactile pressures” di Barry G. Green). L’illusione di Weber è stata registrata attraverso l’output delle reti neurali, e poi rappresentata graficamente, cercando di spiegare le ragioni di tali risultati.

Study of Italian isolates of Alternaria spp.: molecular and morphological characterization and pathogenesis on apple tree

It was decided to carry out a morphological and molecular characterization of the Italian Alternaria isolatescollected from apple , and evaluate their pathogenicity and subsequently combining the data collected. The strain collection (174 isolates) was constructed by collecting material (received from extension service personnel) between June and August of 2007, 2008, and 2009. A Preliminary bioassays were performed on detached plant materials (fruit and leaf wounded and unwounded), belonging to the Golden cultivar, with two different kind of inoculation (conidial suspension and conidial filtrate). Symptoms were monitored daily and a value of pathogenicity score (P.S.) was assigned on the basis of the diameter of the necrotic area that developed. On the basis of the bioassays, the number of isolates to undergo further molecular analysis was restricted to a representative set of single spore strains (44 strains). Morphological characteristics of the colony and sporulation pattern were determined according to previous systematic work on small-spored Alternaria spp. (Pryor and Michaelides, 2002 and Hong et al., 2006). Reference strains (Alternaria alternata, Alternaria tenuissima, Alternaria arborescens and four Japanese strains of Alternaria alternata mali pathotype), used in the study were kindly provided by Prof. Barry Pryor, who allows a open access to his own fungal collection. Molecular characterization was performed combining and comparing different data sets obtained from distinct molecular approach: 1) investigation of specific loci and 2) fingerprinting based on diverse randomly selected polymorphic sites of the genome. As concern the single locus analysis, it was chosen to sequence the EndoPG partial gene and three anonymous region (OPA1-3, OPA2- and OPa10-2). These markers has revealed a powerful tool in the latter systematic works on small-spored Alternaria spp. In fact, as reported in literature small-spored Alternaria taxonomy is complicated due to the inability to resolve evolutionary relationships among the taxa because of the lack of variability in the markers commonly used in fungi systematic. The three data set together provided the necessary variation to establish the phylogenetic relationships among the Italian isolates of Alternaria spp. On Italian strains these markers showed a variable number of informative sites (ranging from 7 for EndoPg to 85 for OPA1-3) and the parsimony analysis produced different tree topologies all concordant to define A. arborescens as a mophyletic clade. Fingerprinting analysis (nine ISSR primers and eight AFLP primers combination) led to the same result: a monophyleic A. arborescens clade and one clade containing both A. tenuissima and the A. alternata strains. This first attempt to characterize Italian Alternaria species recovered from apple produced concordant results with what was already described in a similar phylogenetic study on pistachio (Pryor and Michaelides, 2002), on walnut and hazelnut (Hong et al., 2006), apple (Kang et al., 2002) and citurus (Peever et al., 2004). Together with these studies, this research demonstrates that the three morphological groups are widely distributed and occupy similar ecological niches. Furthermore, this research suggest that these Alternaria species exhibit a similar infection pattern despite the taxonomic and pathogenic differences. The molecular characterization of the pathogens is a fundamental step to understanding the disease that is spreading in the apple orchards of the north Italy. At the beginning the causal agent was considered as Alteraria alternata (Marshall and Bertagnoll, 2006). Their preliminary studies purposed a pathogenic system related to the synthesis of toxins. Experimental data of our bioassays suggest an analogous hypothesis, considering that symptoms could be induced after inoculating plant material with solely the filtrate from pathogenic strains. Moreover, positive PCR reactions using AM-toxin gene specific primers, designed for identification of apple infecting Alternaria pathovar, led to a hypothesis that a host specific toxin (toxins) were involved. It remains an intriguing challenge to discover or not if the agent of the “Italian disease” is the same of the one previously typified as Alternaria mali, casual agent of the apple blotch disease.

Endovascular treatment of popliteal artery aneurysms: a single-center experience

PURPOSE: To evaluate the use of covered stent-grafts in the endovascular treatment (ET) of popliteal artery aneurysms (PAAs). MATERIALS AND METHODS: A retrospective analysis was conducted over a period of 52 months in 18 consecutive patients (17 men; mean age +/- SD, 70 years +/- 11) undergoing ET of PAAs with the Viabahn endograft in a single center. Patient symptoms, aneurysm characteristics, technical outcomes, complications, and follow-up were assessed. RESULTS: Aneurysm diameters ranged from 12 to 51 mm with a mean of 30 mm (+/-11). Thirteen aneurysms (72.2%) were partially thrombosed and 12 patients (66.6%) had symptoms of lower limb ischemia at presentation (11 chronic and one acute). The technical success rate was 94%. Intraprocedural emboli and endoleak occurred in one and two patients, respectively. Fourteen patients were available for follow-up after successful treatment, with a mean follow-up time of 15 months (range, 7-37 months). All stent-grafts were patent after 1 month, with no mortality or limb loss. The primary patency rate with complete exclusion of the aneurysm at 6 months was 86%. Pre- and postprocedural noninvasive arterial studies were available in 10 patients, demonstrating improvement of the ankle-brachial index from 0.96 +/- 0.41 to 1.17 +/- 0.18, respectively (P = .06). CONCLUSIONS: Endovascular stent-graft repair of PAAs is a feasible treatment option. However, further follow-up studies regarding the durability of results are required.

Improving cup positioning using a mechanical navigation instrument

Although surgical navigation reduces the rate of malpositioned acetabular cups in total hip arthroplasty (THA), its use has not been widely adopted. As a result of our perceived need for simple and efficient methods of navigation, we developed a mechanical navigation device for acetabular cup orientation.

Phase II study of oral capsular 4-hydroxyphenylretinamide (4-HPR/fenretinide) in pediatric patients with refractory or recurrent neuroblastoma: a report from the Children's Oncology Group

To determine the response rate to oral capsular fenretinide in children with recurrent or biopsy proven refractory high-risk neuroblastoma.

Current patch test results with the European baseline series and extensions to it from the 'European Surveillance System on Contact Allergy' network, 2007-2008

The pattern of contact sensitization to the supposedly most important allergens assembled in the baseline series differs between countries, presumably at least partly because of exposure differences. Objectives. To describe the prevalence of contact sensitization to allergens tested in consecutive patients in the years 2007 and 2008, and to discuss possible differences.