Universal Newborn Screening for Congenital Cytomegalovirus Infection - From Infant to Maternal Infection: A Prospective Multicenter Study

Introduction: Most infants at risk for cytomegalovirus (CMV)-associated sensorineural hearing loss (SNHL) are unrecognized because of the absence of a universal neonatal CMV screening. The search of CMV-DNA by molecular methods in salivary swabs was demonstrated to be a reliable approach. This study describes the results obtained by carrying out a universal screening for congenital CMV (cCMV) infection including all live-born newborns in three Italian sites, as well as the therapeutic interventions and clinical outcome of the CMV-infected neonates. Moreover, CMV maternal infection's characteristics were evaluated. Methods: To confirm or exclude cCMV infection, a CMV-DNA-positive result on a first salivary swab was followed by repeated saliva and urine samples collected within 21 days of age. Breast milk samples were also collected. The search of CMV-DNA was performed with a single automated quantitative commercial real-time PCR assay, regardless of the type of samples used. Results: A total of 3,151 newborns were enrolled; 21 (0.66%) of them were congenitally infected (median saliva viral load at screening, 6.65 [range, 5.03-7.17] log10 IU/ml). Very low/low viral load in screening saliva samples (median value, 1.87 [range, 1.14-2.59] log10 IU/ml) was associated with false-positive results (n = 54; 1.7%). CMV-DNA was detected in almost half of the breast milk samples of mother-infant pairs with a false-positive result, suggesting that contamination from breast milk may not be the only explanation in the study population. cCMV infection confirmation with the search of CMV-DNA in a urine sample proved to be the gold standard strategy, since false-positive results were observed in 4/54 (7.5%) of the repeated saliva samples. Symptomatic cCMV infection was observed in 3/21 (14.3%) infants; notably, one (4.7%) developed moderate unilateral SNHL at 5 months after birth. Finally, two symptomatic cCMV infections were associated with primary maternal infection acquired in the first trimester of gestation; one newborn with severe cCMV symptoms was born to a mother with no CMV checkups in pregnancy. Conclusion: Without universal neonatal CMV screening, some infected infants who develop late neurological sequelae may not be recognized and, consequently, they are not able to benefit early from instrumental and therapeutic interventions to limit and/or treat CMV disease

Estudo retrospectivo das afecções locomotoras em ruminantes atendidos na Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo entre 2000 e 2012

This study aimed to perform a retrospective study of ruminants attended at the Clinic for Cattle and Small Ruminants (CBPR) of the Faculty of Veterinary Medicine (FMVZ), University of São Paulo (USP) with locomotor diseases from 2000 to 2012. During this period 209 cases were treated. It was found that cases located in the distal limb and in the proximal region were 62.7% and 33.7%, respectively. In bovines, 121 (57.9%) cases were treated, with 86 (71.07%) cases presented in the distal limb and 35 (28.93%) cases in the proximal region. The most common disease was interdigital hyperplasia with 23 (26.74%) cases treated. Fractures were the most frequent disease related to the proximal region corresponding to 17 (48.6%) occurrences. In small ruminants, 88 animals (42.1%) were treated with 45 (51.1%) cases in the distal region and the other 43 (48.9%) in the proximal region. In these species, the foot-rot (60%) and fractures (77.4%) was the most common diseases found in the distal and the proximal region, respectively. The disorders of the locomotor system of ruminants were uncommon in the CBPR. While the affected animals with claw diseases have a good prognosis, disorders affecting the upper limb in cattle, mainly fracture, have a poor prognosis.Foi realizado o estudo retrospectivo das afecções do sistema locomotor de ruminantes atendidos no Serviço de Clínica de Bovinos e Pequenos Ruminantes da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo (FMVZ-USP), no período de 2000 a 2012. Nesse período, foram atendidos 209 casos de animais com problemas locomotores, dos quais 62,7% localizados na região distal dos membros e 37,3% na região proximal. Na espécie bovina, com 121 (57,9%) casos atendidos, o comprometimento da região distal dos membros foi observado em 86 (71,07%) e da região proximal em 35 (28,93%) dos casos, respectivamente. A afecção mais frequente observada em bovinos foi a hiperplasia interdigital com 26,74% (23) dos casos atendidos. Entre as afecções na região proximal, houve maior ocorrência de fraturas, com 48,6% (17) dos casos. Foram atendidos 88 (42,1%) pequenos ruminantes, apresentando lesões na região distal em 51,1% (45) dos casos e 48,9% (43) com lesões na região proximal. Nessas espécies, as lesões de maior ocorrência nas regiões distais e proximais foram, respectivamente, o foot-rot (60%) e as fraturas (77,4%). As afecções do sistema locomotor dos ruminantes foram pouco frequentes entre os animais atendidos no período estudado. Quanto ao prognóstico, foi bom nos animais acometidos com doenças podais, diferentemente das afecções proximais dos bovinos, principalmente fraturas, que apresentaram prognóstico mau

Molecular purging of multiple myeloma cells by ex-vivo culture and retroviral transduction of mobilized-blood CD34+ cells

<p>Abstract</p> <p>Background</p> <p>Tumor cell contamination of the apheresis in multiple myeloma is likely to affect disease-free and overall survival after autografting.</p> <p>Objective</p> <p>To purge myeloma aphereses from tumor contaminants with a novel culture-based purging method.</p> <p>Methods</p> <p>We cultured myeloma-positive CD34⁺PB samples in conditions that retained multipotency of hematopoietic stem cells, but were unfavourable to survival of plasma cells. Moreover, we exploited the resistance of myeloma plasma cells to retroviral transduction by targeting the hematopoietic CD34⁺cell population with a retroviral vector carrying a selectable marker (the truncated form of the human receptor for nerve growth factor, ΔNGFR). We performed therefore a further myeloma purging step by selecting the transduced cells at the end of the culture.</p> <p>Results</p> <p>Overall recovery of CD34⁺cells after culture was 128.5%; ΔNGFR transduction rate was 28.8% for CD34⁺cells and 0% for CD138-selected primary myeloma cells, respectively. Recovery of CD34⁺cells after ΔNGFR selection was 22.3%. By patient-specific Ig-gene rearrangements, we assessed a decrease of 0.7–1.4 logs in tumor load after the CD34⁺cell selection, and up to 2.3 logs after culture and ΔNGFR selection.</p> <p>Conclusion</p> <p>We conclude that <it>ex-vivo </it>culture and retroviral-mediated transduction of myeloma leukaphereses provide an efficient tumor cell purging.</p

Il Futuro della Cybersecurity in Italia: Ambiti Progettuali Strategici

Il presente volume nasce come continuazione del precedente, con l’obiettivo di delineare un insieme di ambiti progettuali e di azioni che la comunità nazionale della ricerca ritiene essenziali a complemento e a supporto di quelli previsti nel DPCM Gentiloni in materia di sicurezza cibernetica, pubblicato nel febbraio del 2017. La lettura non richiede particolari conoscenze tecniche; il testo è fruibile da chiunque utilizzi strumenti informatici o navighi in rete. Nel volume vengono considerati molteplici aspetti della cybersecurity, che vanno dalla definizione di infrastrutture e centri necessari a organizzare la difesa alle azioni e alle tecnologie da sviluppare per essere protetti al meglio, dall’individuazione delle principali tecnologie da difendere alla proposta di un insieme di azioni orizzontali per la formazione, la sensibilizzazione e la gestione dei rischi. Gli ambiti progettuali e le azioni, che noi speriamo possano svilupparsi nei prossimi anni in Italia, sono poi accompagnate da una serie di raccomandazioni agli organi preposti per affrontare al meglio, e da Paese consapevole, la sfida della trasformazione digitale. Le raccomandazioni non intendono essere esaustive, ma vanno a toccare dei punti che riteniamo essenziali per una corretta implementazione di una politica di sicurezza cibernetica a livello nazionale. Politica che, per sua natura, dovrà necessariamente essere dinamica e in continua evoluzione in base ai cambiamenti tecnologici, normativi, sociali e geopolitici. All’interno del volume, sono riportati dei riquadri con sfondo violetto o grigio; i primi sono usati nel capitolo introduttivo e nelle conclusioni per mettere in evidenza alcuni concetti ritenuti importanti, i secondi sono usati negli altri capitoli per spiegare il significato di alcuni termini tecnici comunemente utilizzati dagli addetti ai lavori. In conclusione, ringraziamo tutti i colleghi che hanno contribuito a questo volume: un gruppo di oltre 120 ricercatori, provenienti da circa 40 tra Enti di Ricerca e Università, unico per numerosità ed eccellenza, che rappresenta il meglio della ricerca in Italia nel settore della cybersecurity. Un grazie speciale va a Gabriella Caramagno e ad Angela Miola che hanno contribuito a tutte le fasi di produzione del libro. Tra i ringraziamenti ci fa piacere aggiungere il supporto ottenuto dai partecipanti al progetto FILIERASICURA