This study was supported by grants from the American Medical Society for Sports Medicine. The authors would like to acknowledge and show our appreciation for our undergraduate research students including David Lawton, Drew Gardner, Mark Sundman, Kelsey Evans, Graham Cochrane, Jordan Cottle and Jack Halligan for their assistance in data collection over the past four years.

Tutte le procedure descritte qui di seguito sono stati approvati dal Institutional Review Board della Elon. 1. computerizzata Neurocognitive Testing <ol><li> Chiedere ai partecipanti di essere seduti davanti al computer. Accedere ai partecipanti al sistema e di istruirli a completare il test neuropsicologici computerizzato che consiste di una sezione demografiche e lo sfondo informazioni, auto-riferito sintomi checklist, e 6 moduli (discriminazione parola, memoria di progettazione, di di X e O, simbolo di corrispondenza, Corrispondenza colore, e tre lettere). </li><li> Scarica relazione di sintesi e inserire quattro punteggi compositi per la memoria verbale, memoria visiva, tempo di reazione e la velocità di elaborazione del motore. </li></ol> 2. eventi correlati Potenziali <ol><li> Misurare la circonferenza testa con un nastro di misurazione per determinare la dimensione di EEG rete da utilizzare. Determinare il posizionamento della rete EEG misurando punti di repere anatomici. </li><li> Immergere la rete EEG in modoluzione di cloruro di sodio e shampoo bambino per 5 min. </li><li> Posizionare la rete EEG sulla testa del partecipante. Il sistema che usiamo comprende 32 canali. </li><li> Controllare i livelli di impedenza dei siti sul computer. Per il nostro sistema, un&#39;impedenza inferiore a 100 kohm è considerato accettabile. </li><li> Spiegare i compiti cognitivi e lasciare che il partecipante pratica ciascuno dei compiti. <ol><li> Auditory Oddball Compito: Istruire il partecipante di mettere le cuffie e sedersi comodamente ad un tavolo. Informare loro che sentiranno una serie di toni bassi e alti e di rispondere più velocemente e accuratamente possibile facendo clic su un pulsante per un tono uditivo ad alta frequenza. </li><li> Flanker Task: Istruire partecipante a sedersi di fronte allo schermo di un computer in cui sia data loro una serie di frecce proiettate su uno schermo. Istruire i partecipanti a rispondere alla direzione della freccia centrale facendo clic con il tasto sinistro del mouse, se è stato che punta a sinistra o cliccando il tasto destro del mouse, se si puntava right più rapidamente e accuratamente possibile. </li></ol></li><li> Istruire partecipante di completare due prove sia uditivo compito eccentrico e il compito flanker. </li><li> Rimuovere la rete EEG dal partecipante e pulire la rete EEG immergendo in germicida disinfettante per 10 min. </li></ol> 3. somatosensoriali percettive Risposte <ol><li> Posizionare la partecipante comodamente con la mano sinistra in posizione prona di riposo sul dispositivo stimolo sensoriale e le dita posizionate lungo il contorno del dispositivo con le punte imbottite di cifre 2 e 3 posti a contatto con le sonde di stimolo. 23 </li><li> Chiedere al partecipante di visualizzare le istruzioni e indicazioni relativi alle attività sul monitor di un computer e inserire le risposte con un due pulsanti del mouse del computer. Progetto 5 diverse prove: 2 semplici compiti singoli tempi di reazione sito, una discriminazione di ampiezza sito doppia, 24 un duplice compito di ampiezza sito con un unico sito adattamento stimolo, 24 eun giudizio ordine temporale compito. 25 </li><li> Prima dell&#39;inizio di ogni prova, gli spunti sul computer daranno istruzioni alla partecipante per completare le prove di pratica per familiarizzare con il compito. Il computer darà le valutazioni prestazioni partecipanti dopo ogni prova (ad esempio, corretto, scorretto). </li></ol> 4. Balance Protocol <ol><li> Istruire i partecipanti a mettere su calze antiscivolo e poi stare sul sistema di equilibrio di conoscere strumento. </li><li> Istruire i partecipanti a stare in una posizione comoda, che corrisponde al centro di dot pressione con il punto centrale dello schermo. I ricercatori registrano questo confortevole posizione di partenza in modo tale che tutti i test si svolgono con la stessa posizione del piede, mentre in piedi sul dispositivo. </li><li> Chiedere al partecipante riposare per 30 secondi per ciascuna delle quattro condizioni (occhi aperti superficie / ferma, gli occhi chiusi / superficie stabile, superficie occhi aperti / schiuma, gli occhi chiusi / superficie di schiuma). Fornire ai partecipanti un 10 secondi di riposo tra ogni condizione e 3 sec conto alla rovescia prima dell&#39;inizio di ogni registrazione. </li><li> Ripetere ciascuna delle condizioni, mentre il completamento di un compito secondario. Chiedere loro di contare all&#39;indietro da 7 a partire da un numero casuale a 3 cifre dato loro (ad esempio, 843). </li><li> Registrare un punteggio di indice ondeggiamento, una misura della deviazione standard della quantità di oscillazione per ogni condizione e centro di dati di pressione da utilizzare in seguito per ulteriori analisi. </li></ol> 5. Gait Valutazione <ol><li> Valutare &#39;andatura con un portatile 15&#39; partecipanti sistema di analisi del cammino strumentato lungo tappeto con sensori di pressione presenti per tutta la lunghezza del tappeto per rilevare footfalls del partecipante. </li><li> Fare i partecipanti attraversare stuoia nudi a una velocità confortevole cinque volte partendo da una distanza di 3 &#39;prima dell&#39;inizio del tappeto e 3&#39; dopo aver lasciato il tappetino. </li><li> Istruire il PARTECIPANTS per completare cinque prove supplementari a piedi, mentre il conteggio a ritroso da sette da un numero casuale a 3 cifre per il concomitante cognitivo duplice compito. </li><li> Le variabili dipendenti da ottenere in uscita dalla analisi del cammino sono misure assolute e variabilità di diversi parametri spazio-temporali, come la velocità, cadenza e lunghezza del passo. </li></ol> 6. Genetica <ol><li> Chiedere al partecipante di rimuovere con attenzione il bastone tampone dal contenitore sterile (facendo attenzione a toccare solo la fine del bastone del bastone tampone), spostare il tampone in bocca, e vigorosamente strofinare il tampone interno di entrambe le guance, per un totale di 20 sec . </li><li> Consegnare il bastone tampone per il tecnico che indossa lattice o nitrile. Tenere solo la fine bastone e poi mettere la punta del tampone in una provetta sterile da 1,7 ml (etichettato con solo un numero di identificazione), che viene immediatamente messo in ghiaccio. </li><li> Entro 24 ore il trasferimento dei campioni sono a un -20 ° C freezer. </li><li> Estratto di DNA utilizzandouno standard DNA Purification Kit secondo il protocollo del produttore. Per ottenere un campione più concentrato, dopo l&#39;estrazione, eseguire una precipitazione passo isopropanolo e reidratare DNA in 20 ml di tampone di EDTA (pH 8,0). </li><li> Conservare il DNA estratto a -80 ° C fino al momento dell&#39;analisi genotipizzazione utilizzando standard di reazione a catena della polimerasi (PCR) test con tag fluorescenti. </li><li> &quot;Call&quot; i genotipi di software PCR e quindi verificare manualmente la visualizzazione di grafici di amplificazione PCR. </li></ol>

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The authors declare that they have no competing financial interests.

L&#39;obiettivo di questo approccio multidimensionale al test commozione cerebrale di base è duplice: 1) per capire meglio l&#39;impatto di una commozione cerebrale (termine acuta e lunga) sul sistema neuromuscolare; 2) per aiutare la medicina dello sport del personale fanno tornare a giocare le decisioni (che principalmente usano test neurocognitivi, come è stato suggerito da McCrory). 26 Tale approccio poliedrico per concussione valutazione fornisce preziose informazioni relative alla eziologia, cambiamen...

Commozioni cerebrali si verificano a tassi allarmanti negli Stati Uniti e hanno raccolto un sacco di attenzione come un problema di salute pubblica. 1-3 Centri statunitensi per il Controllo delle Malattie e la Prevenzione (CDC) stima che 1,6-3.800.000 commozioni cerebrali si verificano in attività sportive e ricreative 4,5 Commozione cerebrale come definito dalla dichiarazione 2013 concussione Consensus 2 &quot;può essere causata da un colpo diretto alla testa, viso, collo o altre parti del corpo con una forza &#39;impulsiva&#39; trasmessa alla testa.&quot; Commozione cerebrale può annualmente. determinassero cambiamenti neuropatologici e / o substrutturali che possono provocare disturbi funzionali. 2 Questi deficit possono persistere per diverse settimane. Non è raro per gli atleti di sperimentare un aumento dei sintomi auto-riferiti, decrementi nel controllo posturale, e ridotta funzione neurocognitiva anche 14 giorni dopo la lesione iniziale. 6 La natura prolungata dei sintomi, l&#39;inindividuazione costante di commozioni, e la variabilità delle capacità pre-lesione spesso portano a decisioni standardizzati complesse e di non ritorno-to-play da parte di medici, tempi di recupero incerti, ed eventualmente sequele a lungo termine. 7-9 A seguito di una commozione cerebrale, un individuo può verificarsi sia a breve termine e gli effetti a lungo termine. Gli effetti a breve termine di traumi sportivi correlati possono includere cambiamenti di giocare abilità, confusione, disturbi della memoria, la perdita di coscienza, rallentamento dei tempi di reazione, perdita di coordinazione, mal di testa, vertigini, vomito, cambiamenti nei modelli di sonno e cambiamenti di umore. Questi sintomi di solito si risolvono nel giro di pochi giorni. 2,10 Tuttavia, mentre alcuni individui recuperare da un unico commozione cerebrale piuttosto rapidamente, molti esperienza persistente effetti che possono durare per settimane o mesi dopo l&#39;infortunio. 10,11, 12 Questi disturbi sintomatici a funzione tutti i giorni può essere quantificato utilizzando cognitivo e delle prestazioni si riferisconoprove d. Mentre nessuno singolo test dovrebbe determinare la diagnosi di una commozione cerebrale, una batteria di test e relazioni note tra test può aiutare il personale medico a fare diagnosi, tornare in aula, e tornare a giocare decisioni. 2 Vi è grande variabilità del rischio di un individuo per commozione cerebrale e il loro recupero corrispondente. 11 I fattori relativi alla commozione cerebrale suscettibilità e recupero naturalmente ora non sono noti o capito. Diversi fattori hanno suggerito che potrebbero avere un impatto suscettibilità commozione cerebrale di un individuo e il recupero. Questi fattori includono la storia dell&#39;individuo commozione cerebrale, la gravità della lesione iniziale, la storia di emicrania, la storia di difficoltà di apprendimento, la storia di comorbidità psichiatriche, e fattori genetici eventualmente. 7, 9, 13, 14 Molti studi hanno indagato individualmente fattori specifici sia per il breve e lungo termine effetticommozioni cerebrali, ovviamente i tempi di recupero, e la genetica come fattore di commozioni cerebrali. 4,8,15-17 Ciò che non è stata chiaramente stabilita è un approccio multiforme efficace per concussione di valutazione che forniscano informazioni preziose relative al eziologia, cambiamenti funzionali, e il recupero dalla commozione cerebrale. Data la varietà di sintomi e il decorso incerto recupero, un approccio multiforme alla valutazione commozione cerebrale è garantito e questo dovrebbe includere test di base di tutti gli atleti prima della partecipazione nella pratica e la concorrenza, nonché tempestivo lesioni valutazione a posteriori. Una recente revisione suggerisce che le valutazioni neurocognitive possono essere più sensibili al recupero da una commozione cerebrale di controllo dei sintomi da solo. 18 Può darsi che ci siano altre misure oggettive che possono essere migliori indicatori di recupero da commozione cerebrale. Per questo protocollo, utilizziamo diversi compiti per valutare i vari componenti del sistema per vedere come vengono influenzati bya commozione cerebrale. Un test neurocognitivi computerizzato in grado di valutare la memoria, la velocità di elaborazione, capacità di problem solving, l&#39;efficienza cognitiva e il controllo degli impulsi. 6 EEG con compiti di elaborazione uditiva e visiva può essere utilizzato per valutare neuroefficiency attraverso l&#39;esame dei potenziali evento correlati. 19 Un&#39;attività discriminazione somatosensoriale può essere utilizzato per valutare le capacità di elaborazione sensoriali periferiche e centrali. 20 misure equilibrio e l&#39;andatura può essere utilizzato per valutare le capacità di prestazioni funzionali. 6,21 Inoltre, valutiamo diversi genotipi che possono avere relazioni di concussione funzione cognitiva storia, il recupero e commozione cerebrale. 22 Noi test di base i nostri varsity studenti-atleti in questa serie di test e ripetere le prove se comportano una commozione cerebrale durante asintomatica. Lo scopo di questo progetto è quello di valutare a breve e lungo termine decrementi potenziali nelle prestazioni a causa di traumi utilizzando genetica, neurocognitive, elettrofisiologico, comportamentale, somatosensoriale, l&#39;equilibrio e le misure andatura. La comprensione dei meccanismi potenziali che possono essere correlati a vari sintomi e disturbi che si verificano con una commozione cerebrale sono importanti nel favorire la nostra conoscenza commozione cerebrale. Greater knowledgle questi cambiamenti possono in futuro aiuti nella diagnosi commozione cerebrale, nonché gestione di concussione in cui si riferisce di tornare a giocare e tornare al mondo accademico. Tutte le misure descritte di seguito vengono presi al basale (prima partecipazione degli studenti-atleti nello sport). Il nostro protocollo attuale è quello di completare il test neurocognitivi computerizzato a 48 ore con il protocollo di equilibrio, perché crediamo che questi forniscono informazioni utili per quanto riguarda il recupero e il gioco return-to-possibile e ritorno-a-accademici. Quando lo studente-atleta riporta asintomatici hanno di nuovo tornare al laboratorio dove vengono ancora effettuate tutte le misure di base, fatta eccezione per i test genetici. Il protocollo completo, basEline e asintomatica, dura circa 90 minuti per completare in un periodo di prova.

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		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Name of Material/ Equipment</td>
			<td style="width:356px;">Company</td>
			<td style="width:119px;">Catalog Number</td>
			<td style="width:167px;">Comments/Description</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:216px;">ImPACT</td>
			<td style="width:356px;">ImPACT, Pittsburgh, PA</td>
			<td style="width:119px;"></td>
			<td>Neurocognitive concussion testing</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">EEG</td>
			<td style="width:356px;">EGI, Eugene, OR</td>
			<td style="width:119px;"></td>
			<td>EEG 32-channel system</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Stim2</td>
			<td style="width:356px;">Compumedics Neuroscan, Charlotte, NC</td>
			<td style="width:119px;"></td>
			<td>Software for task presentation for flanker task and auditory oddball</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">NetStation</td>
			<td style="width:356px;">EGI, Eugene, OR</td>
			<td style="width:119px;"></td>
			<td>Software for data collection and analysis of EEG</td>
		</tr>
		<tr height="17">
			<td height="17" style="height:17px;width:216px;">Sensory Device</td>
			<td style="width:356px;">Cortical Metrics</td>
			<td style="width:119px;"></td>
			<td>Sensory testing</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Balance System SD</td>
			<td>Biodex Medical Systems, Inc., Shirley, NY</td>
			<td style="width:119px;"></td>
			<td>balance testing</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Force Plate</td>
			<td>AMTI Corp., Watertown, MA, USA</td>
			<td style="width:119px;"></td>
			<td>Gait Initiation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Movement Analysis</td>
			<td>Qualisys AB, Gothenburg, Sweden</td>
			<td style="width:119px;"></td>
			<td>Gait Analysis</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">GAITRite&#160;</td>
			<td style="width:356px;">CIR systems, Inc., Sparta, NJ, USA</td>
			<td style="width:119px;"></td>
			<td>Gait analysis</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:216px;">PCR</td>
			<td style="width:356px;">Applied Biosystems, Foster City, CA</td>
			<td style="width:119px;"></td>
			<td>Genetic Analysis</td>
		</tr>
		<tr height="24">
			<td height="24" style="height:24px;">Matlab</td>
			<td style="width:356px;">Mathworks, Natick, MA, USA</td>
			<td style="width:119px;"></td>
			<td>Gait and balance analysis</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:216px;">Visual 3D</td>
			<td style="width:356px;">C Motion, Inc, Germantown, MD, USA</td>
			<td style="width:119px;"></td>
			<td>3D analysis&#160;</td>
		</tr>
	</tbody>
</table>

a neuroscientific approach to the examination of concussions in student-athletes

Commozioni cerebrali si verificano a tassi allarmanti negli Stati Uniti e sono diventati un serio problema di salute pubblica. Il CDC stima che 1,6-3.800.000 commozioni cerebrali si verificano in attività sportive e ricreative ogni anno. Commozione cerebrale come definito dal 2013 concussione Consensus Statement &quot;può essere causata da un colpo diretto alla testa, viso, collo o altre parti del corpo con una forza &#39;impulsiva&#39; trasmessa alla testa.&quot; Concussions lasciano l&#39;individuo sia a breve ed effetti a lungo termine. Gli effetti a breve termine di traumi sportivi correlati possono includere cambiamenti di giocare abilità, confusione, disturbi della memoria, la perdita di coscienza, rallentamento dei tempi di reazione, perdita di coordinazione, mal di testa, vertigini, vomito, cambiamenti nei modelli di sonno e cambiamenti di umore. Questi sintomi di solito si risolvono nel giro di pochi giorni. Tuttavia, mentre alcuni individui recuperare da un unico commozione cerebrale piuttosto rapidamente, molti esperienza persistente effetti che possonodurare per settimane o mesi. I fattori legati alla commozione cerebrale suscettibilità e dei tempi di recupero successive non sono ben noti o capito in questo momento. Diversi fattori sono stati suggeriti e comprendono la storia dell&#39;individuo commozione cerebrale, la gravità della lesione iniziale, la storia di emicrania, la storia di difficoltà di apprendimento, la storia di comorbidità psichiatriche, e possibilmente, fattori genetici. Molti studi hanno indagato individualmente alcuni fattori sia a breve termine ea lungo termine effetti di traumi, ovviamente i tempi di recupero, la suscettibilità e il recupero. Ciò che non è stato stabilito chiaramente è un approccio multiforme efficace alla valutazione commozione cerebrale che avrebbe prodotto preziose informazioni relative alla eziologia, cambiamenti funzionali, e il recupero. Lo scopo di questo manoscritto è quello di mostrare uno di questi molteplici avvicinato che esamina commozioni utilizzando computerizzato test neurocognitivi, potenziali evento correlati, risposte percettive somatosensoriale, equilibrio asinivalu-, la valutazione andatura e test genetici.

Computerizzato test neurocognitivi Un esempio dei risultati per il test neurocognitivi computerizzato può essere visto in Figura 1. Il programma informatico suscita punteggi compositi sul verbale di memoria, memoria visiva, Visual velocità motore e il tempo di reazione, che sono spesso utilizzati per fare ritorno-to-play e tornare a -Imparare protocolli di gestione commozione cerebrale. I compositi memoria verbale e visiva valutare processi attentivi, l&#3...

Watch this Scientific Journal Video about A Neuroscientific Approach to the Examination of Concussions in Student-Athletes at JoVE.com

A Neuroscientific Approach to the Examination of Concussions in Student-Athletes

Vi è grande variabilità del rischio di un individuo per commozione cerebrale e il loro recupero corrispondente. Un approccio multiforme alla valutazione concussione è giustificata; compresi test di base degli atleti prima della partecipazione allo sport e tempestivo lesioni valutazione successiva. L&#39;obiettivo di questo protocollo è quello di fornire un approccio multiforme esaminare commozioni cerebrali.

Un approccio neuroscientifica all&#39;esame di traumi in studenti-atleti

Concussions are occurring at alarming rates in the United States and have become a serious public health concern. The CDC estimates that 1.6 to 3.8 ...

a-neuroscientific-approach-to-examination-concussions-student

Research

JoVE Journal

Medicine

12.6K Views.  Elon University.  Vi è grande variabilità del rischio di un individuo per commozione cerebrale e il loro recupero corrispondente. Un approccio multiforme alla valutazione concussione è giustificata; compresi test di base degli atleti prima della partecipazione allo sport e tempestivo lesioni valutazione successiva. L'obiettivo di questo protocollo è quello di fornire un approccio multiforme esaminare commozioni cerebrali. 

Video: A Neuroscientific Approach to the Examination of Concussions in Student-Athletes

Bronchial Thermoplasty:  A Novel Therapeutic Approach to Severe Asthma

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled manner to reduce excessive airway smooth muscle. Reducing airway smooth muscle decreases the ability of the airways to constrict, thereby reducing the frequency of asthma attacks. Bronchial thermoplasty is delivered by the Alair System and is performed in three outpatient procedure visits, each scheduled approximately three weeks apart. The first procedure treats the airways of the right lower lobe, the second treats the airways of the left lower lobe and the third and final procedure treats the airways in both upper lobes. After all three procedures are performed the bronchial thermoplasty treatment is complete.
Bronchial thermoplasty is performed during bronchoscopy with the patient under moderate sedation. All accessible airways distal to the mainstem bronchi between 3 and 10 mm in diameter, with the exception of the right middle lobe, are treated under bronchoscopic visualization. Contiguous and non-overlapping activations of the device are used, moving from distal to proximal along the length of the airway, and systematically from airway to airway as described previously. Although conceptually straightforward, the actual execution of bronchial thermoplasty is quite intricate and procedural duration for the treatment of a single lobe is often substantially longer than encountered during routine bronchoscopy. As such, bronchial thermoplasty should be considered a complex interventional bronchoscopy and is intended for the experienced bronchoscopist. Optimal patient management is critical in any such complex and longer duration bronchoscopic procedure. This article discusses the importance of careful patient selection, patient preparation, patient management, procedure duration, postoperative care and follow-up to ensure that bronchial thermoplasty is performed safely.
Bronchial thermoplasty is expected to complement asthma maintenance medications by providing long-lasting asthma control and improving asthma-related quality of life of patients with severe asthma. In addition, bronchial thermoplasty has been demonstrated to reduce severe exacerbations (asthma attacks) emergency rooms visits for respiratory symptoms, and time lost from work, school and other daily activities due to asthma.

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled manner to reduce excessive airway smooth muscle. Reducing airway smooth muscle decreases the ability of the airways to constrict, thereby reducing the frequency of asthma attacks.

Termoplastica bronchiale: un nuovo approccio terapeutico per l&#39;asma grave

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled ...

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Medicina

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia

There are several lines of evidence supporting the role of de novo mutations as a mechanism for common disorders, such as autism and schizophrenia. First, the de novo mutation rate in humans is relatively high, so new mutations are generated at a high frequency in the population. However, de novo mutations have not been reported in most common diseases. Mutations in genes leading to severe diseases where there is a strong negative selection against the phenotype, such as lethality in embryonic stages or reduced reproductive fitness, will not be transmitted to multiple family members, and therefore will not be detected by linkage gene mapping or association studies. The observation of very high concordance in monozygotic twins and very low concordance in dizygotic twins also strongly supports the hypothesis that a significant fraction of cases may result from new mutations. Such is the case for diseases such as autism and schizophrenia. Second, despite reduced reproductive fitness1 and extremely variable environmental factors, the incidence of some diseases is maintained worldwide at a relatively high and constant rate. This is the case for autism and schizophrenia, with an incidence of approximately 1% worldwide. Mutational load can be thought of as a balance between selection for or against a deleterious mutation and its production by de novo mutation. Lower rates of reproduction constitute a negative selection factor that should reduce the number of mutant alleles in the population, ultimately leading to decreased disease prevalence. These selective pressures tend to be of different intensity in different environments. Nonetheless, these severe mental disorders have been maintained at a constant relatively high prevalence in the worldwide population across a wide range of cultures and countries despite a strong negative selection against them2. This is not what one would predict in diseases with reduced reproductive fitness, unless there was a high new mutation rate. Finally, the effects of paternal age: there is a significantly increased risk of the disease with increasing paternal age, which could result from the age related increase in paternal de novo mutations. This is the case for autism and schizophrenia3. The male-to-female ratio of mutation rate is estimated at about 4&#x2013;6:1, presumably due to a higher number of germ-cell divisions with age in males. Therefore, one would predict that de novo mutations would more frequently come from males, particularly older males4. A high rate of new mutations may in part explain why genetic studies have so far failed to identify many genes predisposing to complexes diseases genes, such as autism and schizophrenia, and why diseases have been identified for a mere 3% of genes in the human genome. Identification for de novo mutations as a cause of a disease requires a targeted molecular approach, which includes studying parents and affected subjects. The process for determining if the genetic basis of a disease may result in part from de novo mutations and the molecular approach to establish this link will be illustrated, using autism and schizophrenia as examples.

Molecular genetic strategy for finding de novo mutations causing common disorders such as autism and schizophrenia.

Una strategia per identificare le mutazioni de novo nei disturbi comuni come autismo e schizofrenia

There are several lines of evidence supporting the role of de novo mutations as a mechanism for common disorders, such as autism and schizophrenia. First, ...

The Measurement and Treatment of Suppression in Amblyopia

Amblyopia, a developmental disorder of the visual cortex, is one of the leading causes of visual dysfunction in the working age population. Current estimates put the prevalence of amblyopia at approximately 1-3%1-3, the majority of cases being monocular2. Amblyopia is most frequently caused by ocular misalignment (strabismus), blur induced by unequal refractive error (anisometropia), and in some cases by form deprivation.
Although amblyopia is initially caused by abnormal visual input in infancy, once established, the visual deficit often remains when normal visual input has been restored using surgery and/or refractive correction. This is because amblyopia is the result of abnormal visual cortex development rather than a problem with the amblyopic eye itself4,5 . Amblyopia is characterized by both monocular and binocular deficits6,7 which include impaired visual acuity and poor or absent stereopsis respectively. The visual dysfunction in amblyopia is often associated with a strong suppression of the inputs from the amblyopic eye under binocular viewing conditions8. Recent work has indicated that suppression may play a central role in both the monocular and binocular deficits associated with amblyopia9,10 .
Current clinical tests for suppression tend to verify the presence or absence of suppression rather than giving a quantitative measurement of the degree of suppression. Here we describe a technique for measuring amblyopic suppression with a compact, portable device11,12 . The device consists of a laptop computer connected to a pair of virtual reality goggles. The novelty of the technique lies in the way we present visual stimuli to measure suppression. Stimuli are shown to the amblyopic eye at high contrast while the contrast of the stimuli shown to the non-amblyopic eye are varied. Patients perform a simple signal/noise task that allows for a precise measurement of the strength of excitatory binocular interactions. The contrast offset at which neither eye has a performance advantage is a measure of the "balance point" and is a direct measure of suppression. This technique has been validated psychophysically both in control13,14 and patient6,9,11 populations.
In addition to measuring suppression this technique also forms the basis of a novel form of treatment to decrease suppression over time and improve binocular and often monocular function in adult patients with amblyopia12,15,16 . This new treatment approach can be deployed either on the goggle system described above or on a specially modified iPod touch device15.

Amblyopia is a developmental disorder of the visual cortex that is often accompanied by strong suppression of one eye. We present a new technique for measuring and treating interocular suppression in patients with amblyopia that can be deployed using virtual reality goggles or a portable iPod Touch device.

La misurazione e trattamento di soppressione in Ambliopia

Amblyopia, a developmental disorder of the visual cortex, is one of the leading causes of visual dysfunction in the working age population. Current ...

Clinical Examination Protocol to Detect Atypical and Classical Scrapie in Sheep

The diagnosis of scrapie, a transmissible spongiform encephalopathy (TSEs) of sheep and goats, is currently based on the detection of disease-associated prion protein by post mortem tests. Unless a random sample of the sheep or goat population is actively monitored for scrapie, identification of scrapie cases relies on the reporting of clinical suspects, which is dependent on the individual&#39;s familiarization with the disease and ability to recognize clinical signs associated with scrapie. Scrapie may not be considered in the differential diagnosis of neurological diseases in small ruminants, particularly in countries with low scrapie prevalence, or not recognized&#160;if it presents as nonpruritic form like atypical scrapie. To aid in the identification of clinical suspects, a short examination protocol is presented to assess the display of specific clinical signs associated with pruritic and nonpruritic forms of TSEs in sheep, which could also be applied to goats. This includes assessment of behavior, vision (by testing of the menace response), pruritus (by testing the response to scratching), and movement (with and without blindfolding). This may lead to a more detailed neurologic examination&#160;of reporting animals as scrapie suspects. It&#160;could also be used in experimental TSE studies of sheep or goats to evaluate disease progression or to identify clinical end-point.

A short clinical examination protocol is presented to aid in the detection of classical and atypical scrapie in sheep and goats.

Protocollo di esame clinico per rilevare la scrapie atipica e classica negli ovini

The diagnosis of scrapie, a transmissible spongiform encephalopathy (TSEs) of sheep and goats, is currently based on the detection of disease-associated ...

Echocardiographic and Histological Examination of Cardiac Morphology in the Mouse

An increasing number of genetically modified mouse models has become available in recent years. Moreover, the number of pharmacological studies performed in mice is high. Phenotypic characterization of these mouse models also requires the examination of cardiac function and morphology. Echocardiography and magnetic resonance imaging (MRI) are commonly used approaches to characterize cardiac function and morphology in mice. Echocardiographic and MRI equipment specialized for use in small rodents is&#160;expensive and requires a dedicated space. This protocol describes cardiac measurements in mice using a clinical echocardiographic system with a 15 MHz human vascular probe. Measurements are performed on anesthetized adult mice. At least three image sequences are recorded and analyzed for each animal in M-mode in the parasternal short-axis view. Afterwards, cardiac histological examination is performed, and cardiomyocyte diameters are determined on hematoxylin-eosin- or wheat germ agglutinin (WGA)-stained paraffin sections. Vessel density is determined morphometrically after Pecam-1 immunostaining. The protocol has been applied successfully to pharmacological studies and different genetic animal models under baseline conditions, as well as after experimental myocardial infarction by the permanent ligation of the left anterior descending coronary artery (LAD). In our experience, echocardiographic investigation is limited to anesthetized animals and is feasible in adult mice weighing at least 25 g.

Echocardiographic examination is frequently used in mice. Expensive high-resolution ultrasound devices have been developed for this purpose. This protocol describes an affordable echocardiographic procedure combined with histological morphometric analyses to determine cardiac morphology.

Esame ecocardiografico ed istologico della morfologia cardiaca nel topo

An increasing number of genetically modified mouse models has become available in recent years. Moreover, the number of pharmacological studies performed ...

An In Vitro Approach to Photodynamic Therapy

Photodynamic therapy (PDT) is a medical procedure that involves incubation of an exogenously applied photosensitizer (PS) followed by visible light photoactivation to induce cell apoptosis. The Federal Drug Administration has approved PDT for the treatment of actinic keratosis, and clinical guidelines recommend PDT as a treatment for certain non-melanoma skin cancers and acne vulgaris. PDT is an advantageous therapeutic modality as it is low cost, non-invasive, and associated with minimal adverse events and scaring. In the first step of PDT, a PS is applied and allowed to accumulate intracellularly. Subsequent light irradiation induces reactive oxygen species formation, which may ultimately lead to cell apoptosis, membrane disruption, mitochondrial damage, immune modulation, keratinocyte proliferation, and collagen turnover. Herein, we present an in vitro method to study PDT in an adherent cell line. This treatment protocol is designed to simulate PDT and may be adjusted to studying the use of PDT with various cell lines, photosensitizers, incubation temperatures, or photoactivation wavelengths. Squamous cell carcinoma cells were incubated with 0, 0.5, 1.0, and 2 mM 5-aminolevulinic acid (5-ALA) for 30 min and photoactivated with 417 nm blue light for 1,000 s. The primary outcome measure was apoptosis and necrosis, as measured by annexin-V and 7-aminoactinomycin D flow cytometry. There was a dose-dependent increase in cell apoptosis following thirty-minute incubation of 5-ALA. To achieve high inter-test validity, it is important to maintain consistent incubation and light parameters when performing in vitro PDT experiments. PDT is a useful clinical procedure and in vitro research may allow for the development of novel PSs, optimization of protocols, and new indications for PDT.

An In Vitro Approach to Photodynamic Therapy

Photodynamic therapy (PDT) is a medical procedure that involves incubation of an exogenously applied photosensitizer (PS) followed by visible light photoactivation to induce apoptosis. We present an in vitro PDT protocol designed to simulate PDT that may be used to study differences in PS incubation and light treatment parameters.

Un approccio In Vitro alla terapia fotodinamica

Photodynamic therapy (PDT) is a medical procedure that involves incubation of an exogenously applied photosensitizer (PS) followed by visible light ...

A Metadata Extraction Approach for Clinical Case Reports to Enable Advanced Understanding of Biomedical Concepts

Clinical case reports (CCRs) are a valuable means of sharing observations and insights in medicine. The form of these documents varies, and their content includes descriptions of numerous, novel disease presentations and treatments. Thus far, the text data within CCRs is largely unstructured, requiring significant human and computational effort to render these data useful for in-depth analysis. In this protocol, we describe methods for identifying metadata corresponding to specific biomedical concepts frequently observed within CCRs. We provide a metadata template as a guide for document annotation, recognizing that imposing structure on CCRs may be pursued by combinations of manual and automated effort. The approach presented here is appropriate for organization of concept-related text from a large literature corpus (e.g., thousands of CCRs) but may be easily adapted to facilitate more focused tasks or small sets of reports. The resulting structured text data includes sufficient semantic context to support a variety of subsequent text analysis workflows: meta-analyses to determine how to maximize CCR detail, epidemiological studies of rare diseases, and the development of models of medical language may all be made more realizable and manageable through the use of structured text data.

We present a protocol and associated metadata template for the extraction of text describing biomedical concepts in clinical case reports. The structured text values produced through this protocol can support deep analysis of thousands of clinical narratives.

Un approccio di estrazione di metadati per rapporti clinici di caso attivare avanzato la comprensione dei concetti biomedicale

Clinical case reports (CCRs) are a valuable means of sharing observations and insights in medicine. The form of these documents varies, and their content ...

A Novel Approach to Monitoring Graft Neovascularization in the Human Gingiva

Laser speckle contrast imaging (LSCI) is a novel method for measuring superficial blood perfusion over large areas. Since it is non-invasive and avoids direct contact with the measured area, it is suitable for monitoring blood flow changes during wound healing in human patients. Vestibuloplasty is periodontal surgery to the oral vestibule, aiming to restore vestibular depth with simultaneous enlargement of the keratinized gingiva. In this special clinical case, a split thickness flap was elevated at the first upper premolar and a xenogenic collagen matrix was adapted to the resulting recipient bed. LSCI was used to monitor the re- and neovascularization of the graft and the surrounding mucosa for one year. A protocol is introduced for the correct adjustment of microcirculation measurement in the oral mucosa, highlighting difficulties and possible failures.
The clinical case study presented demonstrated that &#8212; following the appropriate protocol &#8212; LSCI is a suitable and reliable method for following up microcirculation in a healing wound in the human oral mucosa and gives useful information on graft integration.

This study introduces a protocol for measuring microcirculation in human oral mucosa by laser speckle contrast imaging. The monitoring of wound healing after vestibuloplasty combined with a xenogenic collagen graft is presented on a clinical case.

Un nuovo approccio al monitoraggio dell'innesto neovascolarizzazione nella gengiva umana

Laser speckle contrast imaging (LSCI) is a novel method for measuring superficial blood perfusion over large areas. Since it is non-invasive and avoids ...

Transthoracic Echocardiographic Examination in the Rabbit Model

Large animal models such as the rabbit are valuable for translational preclinical research. Rabbits have a similar cardiac electrophysiology compared to that of humans and that of other large animal models such as dogs and pigs. However, the rabbit model has the additional advantage of lower maintenance costs compared to other large animal models. The longitudinal evaluation of cardiac function using echocardiography, when appropriately implemented, is a useful methodology for preclinical assessment of novel therapies for heart failure with reduced ejection fraction (e.g. cardiac regeneration). The correct use of this non-invasive tool requires the implementation of a standardized examination protocol following international guidelines. Here we describe, step by step, a detailed protocol supervised by veterinary cardiologists for performing echocardiography in the rabbit model, and demonstrate how to correctly obtain the different echocardiographic views and imaging planes, as well as the different imaging modes available in a clinical echocardiography system routinely used in human and veterinary patients.

Here we describe, step by step, a detailed protocol for performing echocardiography in the rabbit model. We show how to correctly obtain the different echocardiographic views and imaging planes, as well as the different imaging modes available in a clinical echocardiography system routinely used in human and veterinary patients.

Esame ecocardiografico transtoracico nel modello del coniglio

Large animal models such as the rabbit are valuable for translational preclinical research. Rabbits have a similar cardiac electrophysiology compared to ...

Indagine su nuovi meccanismi di disfunzione microvascolare nell'uomo

Intradermal Microdialysis: An Approach to Investigating Novel Mechanisms of Microvascular Dysfunction in Humans

The cutaneous vasculature is an accessible tissue that can be used to assess microvascular function in humans. Intradermal microdialysis is a minimally invasive technique used to investigate mechanisms of vascular smooth muscle and endothelial function in the cutaneous circulation. This technique allows for the pharmacological dissection of the pathophysiology of microvascular endothelial dysfunction as indexed by decreased nitric oxide-mediated vasodilation, an indicator of cardiovascular disease development risk. In this technique, a microdialysis probe is placed in the dermal layer of the skin, and a local heating unit with a laser Doppler flowmetry probe is placed over the probe to measure the red blood cell flux. The local skin temperature is clamped or stimulated with direct heat application, and pharmacological agents are perfused through the probe to stimulate or inhibit intracellular signaling pathways in order to induce vasodilation or vasoconstriction or to interrogate mechanisms of interest (co-factors, antioxidants, etc.). The cutaneous vascular conductance is quantified, and mechanisms of endothelial dysfunction in disease states can be delineated.

Autore in primo piano: Un approccio di farmacodissezione per scoprire i meccanismi nelle popolazioni a rischio di malattie cardiovascolari 

Intradermal microdialysis is a minimally invasive technique used to investigate microvascular function in health and disease. Both dose-response and local heating protocols can be utilized for this technique to explore mechanisms of vasodilation and vasoconstriction in the cutaneous circulation.

Microdialisi intradermica: un approccio per studiare nuovi meccanismi di disfunzione microvascolare nell'uomo

The cutaneous vasculature is an accessible tissue that can be used to assess microvascular function in humans. Intradermal microdialysis is a minimally ...