PROTOCOL OF SEDATION AND ANTAGONISM (DEXMEDETOMIDINE-ATIPAMEZOLE) TO PERFORM DIAGNOSTIC ANALGESIA IN FRACTIOUS HORSES : PRELIMINARY STUDY

Purpose of the work: To assess the applicability of a new protocol of sedation and antagonism using dexmedetomidine (DEX) and atipamezole (ATZ) to perform diagnostic analgesia in fractious horses. Materials and methods: Six fractious horses (3 geldings and 3 mares) undergoing lameness investigation that required diagnostic analgesia were recruited. All the horses were admitted two days before the beginning of the study. During this period heart rate (HR), respiratory rate (RR), height of the head from the ground, mucous membranes colour, capillary refill time (CRT) and temperature were recorded. All the horses were sedated with DEX 2.5-5\u3bcg/kg and after 20 min ATZ 5\u3bcg/kg was administered. The degree of sedation was assessed using the visual analogue scale (VAS) and the numerical rating scale (NRS). The FC, FR, TRC were assessed at 3, 5, 10 and 15 min after both sedation and ATZ administration. Statistical analysis: The physiological parameters were analysed using ANOVA whereas Wilcoxon test was used for the sedation scales. Results: The values of HR and RR were significantly different after administration of DEX and ATZ at 3 and 5 min respectively. Statistical significance was also appreciated for height of the head from the ground, ataxia, tactile stimuli and visual stimuli. Ataxia and height of the head from the ground were improved starting from 3 min after administration of ATZ. Conclusion and clinical relevance: The protocol was successful in all cases, however in two patients ataxia was not completely abolished after ATZ administration. There is a potential for the protocol to be used in the everyday practice. However diffusion of the local anaesthetic after block must be born in mind

Fiber transport of spatially entangled photons

Entanglement in the spatial degrees of freedom of photons is an interesting resource for quantum information. For practical distribution of such entangled photons it is desireable to use an optical fiber, which in this case has to support multiple transverse modes. Here we report the use of a hollow-core photonic crystal fiber to transport spatially entangled qubits.Comment: 4 pages, 4 figure

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

T cell receptor sequence clustering and antigen specificity

There has been increasing interest in the role of T cells and their involvement in cancer, autoimmune and infectious diseases. However, the nature of T cell receptor (TCR) epitope recognition at a repertoire level is not yet fully understood. Due to technological advances a plethora of TCR sequences from a variety of disease and treatment settings has become readily available. Current efforts in TCR specificity analysis focus on identifying characteristics in immune repertoires which can explain or predict disease outcome or progression, or can be used to monitor the efficacy of disease therapy. In this context, clustering of TCRs by sequence to reflect biological similarity, and especially to reflect antigen specificity have become of paramount importance. We review the main TCR sequence clustering methods and the different similarity measures they use, and discuss their performance and possible improvement. We aim to provide guidance for non-specialists who wish to use TCR repertoire sequencing for disease tracking, patient stratification or therapy prediction, and to provide a starting point for those aiming to develop novel techniques for TCR annotation through clustering

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

Anestesia locoregionale dell&apos;orecchio nel cavallo: descrizione del blocco tramite l&apos;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

Detectors for the next-generation PET scanners

Next-generation PET scanners are expected to fulfill very high requirements in terms of spatial, energy and timing resolution. Modern scanner performances are inherently limited by the use of standard photomultiplier tubes. The use of Silicon Photomultiplier (SiPM) matrices is proposed for the construction of a small animal PET system with depth of interaction capabilities. Measurements showing that SiPM matrices are highly ideal for PET applications, have been reported

Effects of natural selection and gene conversion on the evolution of human glycophorins coding for MNS blood polymorphisms in malaria-endemic African populations

Malaria has been a very strong selection pressure in recent human evolution, particularly in Africa. Of the one million deaths per year due to malaria, more than 90% are in sub-Saharan Africa, a region with high levels of genetic variation and population substructure. However, there have been few studies of nucleotide variation at genetic loci that are relevant to malaria susceptibility across geographically and genetically diverse ethnic groups in Africa. Invasion of erythrocytes by Plasmodium falciparum parasites is central to the pathology of malaria. Glycophorin A (GYPA) and B (GYPB), which determine MN and Ss blood types, are two major receptors that are expressed on erythrocyte surfaces and interact with parasite ligands. We analyzed nucleotide diversity of the glycophorin gene family in 15 African populations with different levels of malaria exposure. High levels of nucleotide diversity and gene conversion were found at these genes. We observed divergent patterns of genetic variation between these duplicated genes and between different extracellular domains of GYPA. Specifically, we identified fixed adaptive changes at exons 3-4 of GYPA. By contrast, we observed an allele frequency spectrum skewed toward a significant excess of intermediate-frequency alleles at GYPA exon 2 in many populations; the degree of spectrum distortion is correlated with malaria exposure, possibly because of the joint effects of gene conversion and balancing selection. We also identified a haplotype causing three amino acid changes in the extracellular domain of glycophorin B. This haplotype might have evolved adaptively in five populations with high exposure to malaria

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