Advanced radiation measurement techniques in diagnostic radiology and molecular imaging.

This paper reports some technological advances recently achieved in the fields of micro-CT and small animal PET instrumentation. It highlights a balance between image-quality improvement and dose reduction. Most of the recent accomplishments in these fields are due to the use of novel imaging sensors such as CMOS-based X-ray detectors and silicon photomultipliers (SiPM). Some of the research projects carried out at the University of Pisa for the development of such advanced radiation imaging technology are also described

Selection and Modelling of a New Single-Domain Intrabody Against TDP-43

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder associated to deteriorating motor and cognitive functions, and short survival. The disease is caused by neuronal death which results in progressive muscle wasting and weakness, ultimately leading to lethal respiratory failure. The misbehaviour of a specific protein, TDP-43, which aggregates and becomes toxic in ALS patient’s neurons, is supposed to be one of the causes. TDP-43 is a DNA/RNA-binding protein involved in several functions related to nucleic acid metabolism. Sequestration of TDP-43 aggregates is a possible therapeutic strategy that could alleviate or block pathology. Here, we describe the selection and characterization of a new intracellular antibody (intrabody) against TDP-43 from a llama nanobody library. The structure of the selected intrabody was predicted in silico and the model was used to suggest mutations that enabled to improve its expression yield, facilitating its experimental validation. We showed how coupling experimental methodologies with in silico design may allow us to obtain an antibody able to recognize the RNA binding regions of TDP-43. Our findings illustrate a strategy for the mitigation of TDP-43 proteinopathy in ALS and provide a potential new tool for diagnostics

Anestesia locoregionale dell'orecchio nel cavallo: descrizione del blocco tramite l'ausilio di un neurostimolatore

Introduzione. L\u2019esecuzione di procedure diagnostiche e terapeutiche a carico dell\u2019orecchio del ca- vallo \ue8 spesso complicata e frustrante per il veterinario. Ci\uf2 \ue8 particolarmente vero per procedure dolorose quali biopsie o gestione di ferite che richiedono l\u2019immobilit\ue0 del paziente1. A tale propo- sito nell\u2019ambito chirurgico, di grossi e piccoli animali, si \ue8 assistito negli ultimi anni, ad un cre- scente interesse nei confronti di tecniche di analgesia selettiva dell\u2019orecchio. Il blocco diretto di ner- vi che innervano la pinna a livello della base dell\u2019orecchio costituiscono una tecnica in grado di ri- durre lo stress del paziente e il tempo richiesto per l\u2019esecuzione delle procedure1. Nonostante un\u2019ot- tima conoscenza anatomica locale, la corretta localizzazione nervosa viene meno a causa di un\u2019ele- vata variabilit\ue0 individuale1. La stimolazione nervosa periferica (tramite neurostimolatore) permet- te di applicare in modo mirato ed in stretta vicinanza alla fibra nervosa, una serie di stimoli elettri- ci che, provocando una contrazione muscolare, consentono di identificare le strutture di interesse. L\u2019utilizzo del neurostimolatore consente una veloce e precisa localizzazione nervosa e abbassa i ri- schi di lesioni da inoculazione intraneurale. Descrizione del caso. Un cavallo di 9 anni, di 420 Kg viene riferito per drenaggio chirurgico di un otoematoma a carico dello scafo dell\u2019orecchio sinistro. L\u2019innervazione auricolare si compone di 3 nervi fondamentali: branca mandibolare del nervo trigemino, branca auricolopalpebrale del nervo facciale e secondo nervo cervicale o grande auricolare. Si decide quindi per il blocco di questi 3 ner- vi tramite l\u2019utilizzo di un neurostimolatore. Il soggetto viene sedato e lo strumento (Vygon Italia) viene connesso ad un ago atraumatico (22G, 50 mm, 30\ub0), infisso nel punto di repere specifico per i singoli nervi e viene impostato ad una intensit\ue0 di 1.0 mA con una stimolazione di 2 Hz della du- rata di 0.1 ms, per ottenere una contrazione dei muscoli target2. Per anestetizzare la branca mandi- bolare del nervo trigemino l\u2019ago, dopo accurata tricotomia e preparazione asettica della cute del- l\u2019area, viene infisso a livello dell\u2019articolazione temporo-mandibolare con direzione rostro-caudale e latero-mediale fino ad ottenere una contrazione dei muscoli digastrico, pterigoideo mediale e la- terale e massetere (spostamento rostrale della pinna e masticazione). Vengono quindi inoculati 5 ml di mepivacaina cloridrato 2%. Viene poi individuata ed anestetizzata la branca auricolo-palpebrale del nervo facciale. Il suo punto di repere \ue8 rappresentato dalla cresta occipitale e dalla base della pinna, costituita dai margini mediale e laterale dell\u2019elice. Dopo accurata tricotomia e preparazione asettica della cute dell\u2019area, l\u2019ago atraumatico viene inserito al centro del triangolo idealmente di- segnato dai due vertici tra la base della pinna e la cresta occipitale. Con le stesse procedure utiliz- zate precedentemente viene eseguita una stimolazione dei muscoli della pinna e della palpebra su- periore e, una volta ottenuti movimenti auricolari caudorostrali e ammiccamento, vengono inocula- ti 5 ml di mepivacaina cloridrato 2%. Per effettuare il blocco del II nervo cervicale, l\u2019ago atraumatico viene inserito ventrocaudalmente all\u2019ala dell\u2019atlante in direzione lateromediale e leggermente ventrodorsale sino ad ottenere una con- trazione dei muscoli del collo e movimenti di abduzione dell\u2019orecchio. Vengono quindi inoculati 5 ml di mepivacaina cloridrato 2%. Dopo 10 minuti dall\u2019esecuzione di ogni singolo blocco viene testata la sensibilit\ue0 tattile e dolorifi- ca dell\u2019orecchio e, visto l\u2019esito favorevole, si procede all\u2019intervento chirurgico. Conclusioni. Il blocco della branca mandibolare del trigemino, della branca auricolopalpebrale del nervo facciale e della branca auricolare del II nervo cervicale \ue8 risultato di facile esecuzione ed ef- ficace per la desensibilizzazione dell\u2019orecchio in tutta la sua struttura. La tecnica \ue8 stata ben tolle- rata e ha permesso di eseguire in maniera agevole la chirurgia riducendo il dosaggio dei farmaci anestetici utilizzati per l\u2019anestesia generale. Questo tipo di anestesia locoregionale potrebbe essere efficace per effettuare procedure chirurgiche a carico dell\u2019orecchio con la sola sedazione dell\u2019ani- male (drenaggio otoematoma, escissione masse neoplastiche o criochirurgia), ovviando cos\uec ai ri- schi legati all\u2019anestesia generale3. La buona conoscenza anatomica e l\u2019utilizzo dello stimolatore nervoso periferico ha permesso la cor- retta localizzazione nervosa con conseguente desensibilizzazione del sito di chirurgia. L\u2019impiego di anestetici locali a media/lunga durata d\u2019azione consente una riduzione del dolore nel periodo pe- rioperatorio, condizione indispensabile affinch\ue9 diminuisca il rischio di autotraumatismi. In ultima analisi, il blocco dei nervi sopracitati ha permesso non solo l\u2019esecuzione della procedura chirurgica ma anche una miglior gestione del paziente nel periodo post-operatorio

Socio-demographic and clinical characterization of patients with obsessive-compulsive tic-related disorder (OCTD) : An Italian multicenter study

© Copyright by Pacini Editore SrlIn the DSM-5 a new "tic-related" specifier for obsessive compulsive disorder (OCD) has been introduced, highlighting the importance of an accurate characterization of patients suffering from obsessive-compulsive tic-related disorder ("OCTD"). In order to characterize OCTD from a socio-demographic and clinical perspective, the present multicenter study was carried out. The sample consists of 266 patients, divided in two groups with lifetime diagnoses of OCD and OCTD, respectively. OCTD vs OCD patients showed a significant male prevalence (68.5% vs 48.5%; p < .001), a higher rate of psychiatric comorbidities (69.4 vs 50%; p < .001) - mainly with neurodevelopmental disorders (24 vs 0%; p < .001), a lower education level and professional status (middle school diploma: 25 vs 7.6%; full-Time job 44.4 vs 58%; p < .001). Moreover, OCTD vs OCD patients showed significantly earlier age of OCD and psychiatric comorbidity onsets (16.1 ± 10.8 vs 22.1 ± 9.5 years; p < .001, and 18.3 ± 12.8 vs 25.6 ± 9.4: p < .001, respectively). Patients with OCTD patients were treated mainly with antipsychotic and with a low rate of benzodiazepine (74.2 vs 38.2% and 20.2 vs 31.3%, respectively; p < .001). Finally, OCTD vs OCD patients showed higher rates of partial treatment response (58.1 vs 38%; p < .001), lower rates of current remission (35.5 vs 54.8%; p < .001) and higher rates of suicidal ideation (63.2 vs 41.7%; p < .001) and attempts (28.9 vs 8.3%; p < .001). Patients with OCTD report several unfavorable socio-demographic and clinical characteristics compared to OCD patients without a history of tic. Additional studies on larger sample are needed to further characterize OCTD patients from clinical and therapeutic perspectives.Peer reviewedFinal Published versio

Results and applications of SiPM photodetectors from FBK-irst by the DASIPM Collaboration

Silicon Photomultipliers (SiPMs) and SiPM matrices optimized for the detection of blue light have been developed at FBK-irst. The first devices produced are composed of 625 microcells with 40 μm × 40 μm size, in a 1mm × 1mm active area. The devices have a breakdown voltage around 30 V, and a gain about 106. The DASIPM Collaboration is evaluating their performance and possible applications in high-energy physics, space physics and medical imaging. Dedicated front-end electronics are also being developed

Substrate-based atom waveguide using guided two-color evanescent light fields

We propose a dipole-force linear waveguide which confines neutral atoms up to lambda/2 above a microfabricated single-mode dielectric optical guide. The optical guide carries far blue-detuned light in the horizontally-polarized TE mode and far red-detuned light in the vertically-polarized TM mode, with both modes close to optical cut-off. A trapping minimum in the transverse plane is formed above the optical guide due to the differing evanescent decay lengths of the two modes. This design allows manufacture of mechanically stable atom-optical elements on a substrate. We calculate the full vector bound modes for an arbitrary guide shape using two-dimensional non-uniform finite elements in the frequency-domain, allowing us to optimize atom waveguide properties. We find that a rectangular optical guide of 0.8um by 0.2um carrying 6mW of total laser power (detuning +-15nm about the D2 line) gives a trap depth of 200uK for cesium atoms (m_F = 0), transverse oscillation frequencies of f_x = 40kHz and f_y = 160kHz, collection area ~ 1um^2 and coherence time of 9ms. We discuss the effects of non-zero m_F, surface interactions, heating rate, the substrate refractive index, and the limits on waveguide bending radius.Comment: 12 pages, 4 figures, revtex, submitted to Phys. Rev. A Replaced: final version accepted by PRA v.61 Feb 2000. (2 paragraphs added

FunClust: a web server for the identification of structural motifs in a set of non-homologous protein structures

The occurrence of very similar structural motifs brought about by different parts of non homologous proteins is often indicative of a common function. Indeed, relatively small local structures can mediate binding to a common partner, be it a protein, a nucleic acid, a cofactor or a substrate. While it is relatively easy to identify short amino acid or nucleotide sequence motifs in a given set of proteins or genes, and many methods do exist for this purpose, much more challenging is the identification of common local substructures, especially if they are formed by non consecutive residues in the sequence

Electronic control of coherence in a two-dimensional array of photonic crystal surface emitting lasers

We demonstrate a semiconductor PCSEL array that uniquely combines an in-plane waveguide structure with nano-scale patterned PCSEL elements. This novel geometry allows two-dimensional electronically controllable coherent coupling of remote vertically emitting lasers. Mutual coherence of the PCSEL elements is verified through the demonstration of a two-dimensional Young’s Slits experiment. In addition to allowing the all-electronic control of the interference pattern, this type of device offers new routes to power and brightness scaling in semiconductor lasers, and opportunities for all-electronic beam steering

Characteristics of a prototype matrix of Silicon PhotoMultipliers (SiPM)

International audienceThis work reports on the electrical (static and dynamic) as well as on the optical characteristics of a prototype matrix of Silicon Photomultipliers (SiPM). The prototype matrix consists of 4 × 4 SiPM's on the same substrat fabricated at FBK-irst (Trento, Italy). Each SiPM of the matrix has an area of 1 × 1mm2 and it is composed of 625 microcells connected in parallel. Each microcell of the SiPM is a GM-APD (n+/p junction on P+ substrate) with an area of 40 × 40 μm2 connected in series with its integrated polysilicon quenching resistance. The static characteristics as breakdown voltage, quenching resistance, post-breakdown dark current as well as the dynamic characteristics as gain and dark count rate have been analysed. The photon detection efficiency as a function of wavelength and operation voltage has been also estimated