Excess Mortality associated to Influenza epidemic in Portugal, from 2007/2008 to 2014/2015 seasons

Mortality in the north hemisphere is higher in winter than in summer seasons, due to the influenza epidemics as well as cold temperatures. Portuguese influenza surveillance comprises clinical and laboratorial notifications of Influenza-like Illness (ILI) attended in the primary health care units and emergency rooms. Without information on specific cause of deaths in real time, estimation of influenza impact has been accessed using Portuguese Daily Mortality Monitoring System (VDM), that covers all cause mortality of Portuguese population. The aim of this study was to provide excess mortality, potentially associated to Influenza each season (between 2007/08 and 2014/15).

Excess pneumonia and influenza hospitalizations associated with influenza epidemics in Portugal from 1998 to 2015

In Portugal there is no severe acute respiratory infection surveillance system in place. Estimation of influenza burden has been accessed using hospital discharge database that covers the mainland Portuguese population. The objective of this study was to estimate the excess of pneumonia or influenza (P&I) hospitalizations during influenza epidemics from seasons 1998-99 to 2014-15 in mainland Portugal.

Novel strategies for targeting innate immune responses to influenza.

NlmCategory="UNASSIGNED">We previously reported that TLR4(-/-) mice are refractory to mouse-adapted A/PR/8/34 (PR8) influenza-induced lethality and that therapeutic administration of the TLR4 antagonist Eritoran blocked PR8-induced lethality and acute lung injury (ALI) when given starting 2 days post infection. Herein we extend these findings: anti-TLR4- or -TLR2-specific IgG therapy also conferred significant protection of wild-type (WT) mice from lethal PR8 infection. If treatment is initiated 3 h before PR8 infection and continued daily for 4 days, Eritoran failed to protect WT and TLR4(-/-) mice, implying that Eritoran must block a virus-induced, non-TLR4 signal that is required for protection. Mechanistically, we determined that (i) Eritoran blocks high-mobility group B1 (HMGB1)-mediated, TLR4-dependent signaling in vitro and circulating HMGB1 in vivo, and an HMGB1 inhibitor protects against PR8; (ii) Eritoran inhibits pulmonary lung edema associated with ALI; (iii) interleukin (IL)-1β contributes significantly to PR8-induced lethality, as evidenced by partial protection by IL-1 receptor antagonist (IL-1Ra) therapy. Synergistic protection against PR8-induced lethality was achieved when Eritoran and the antiviral drug oseltamivir were administered starting 4 days post infection. Eritoran treatment does not prevent development of an adaptive immune response to subsequent PR8 challenge. Overall, our data support the potential of a host-targeted therapeutic approach to influenza infection.Mucosal Immunology advance online publication 27 January 2016; doi:10.1038/mi.2015.141.

Structural Basis for Clonal Diversity of the Public T Cell Response to Dominant Epitopes from Cytomegalovirus and Influenza

A diverse T cell receptor (TCR) repertoire is a prerequisite for effective viral clearance. However, knowledge of human TCR repertoire to defined viral antigens is limited. Recent advances in high-throughput sequencing (HTS) and single-cell sorting have revolutionized the study of human TCR repertoires to different types of viruses. In collaboration with the laboratory of Dr. Nan-ping Weng (National Institute on Aging, NIH), we applied unique molecular identifier (UMI)-labelled HTS, single-cell paired TCR analysis, surface plasmon resonance, and X-ray crystallography to exhaustively interrogate CD8+ TCR repertoires specific for cytomegalovirus (CMV) and influenza A (Flu) in HLA-A2+ humans. Our two CMV-specific TCR-pMHC structures and two Flu-specific TCR-pMHC structures provide a plausible explanation for the much higher diversity of CMV-specific than Flu-specific TCR repertoires in humans. Our comprehensive biochemical and structural portrait of two different anti-viral T cell responses may contribute to the future development of predictors of immunity or disease at the individual level.

Towards the Knowledge-based Design of Universal Influenza Epitope Ensemble Vaccines

Motivation: Influenza A viral heterogeneity remains a significant threat due to unpredictable antigenic drift in seasonal influenza and antigenic shifts caused by the emergence of novel subtypes. Annual review of multivalent influenza vaccines targets strains of influenza A and B likely to be predominant in future influenza seasons. This does not induce broad, cross protective immunity against emergent subtypes. Better strategies are needed to prevent future pandemics. Cross-protection can be achieved by activating CD8+ and CD4+ T cells against highly-conserved regions of the influenza genome. We combine available experimental data with informatics-based immunological predictions to help design vaccines potentially able to induce cross-protective T-cells against multiple influenza subtypes. Results: To exemplify our approach we designed two epitope ensemble vaccines comprising highlyconserved and experimentally-verified immunogenic influenza A epitopes as putative non-seasonal influenza vaccines; one specifically targets the US population and the other is a universal vaccine. The USA-specific vaccine comprised 6 CD8+ T cell epitopes (GILGFVFTL, FMYSDFHFI, GMDPRMCSL, SVKEKDMTK, FYIQMCTEL, DTVNRTHQY) and 3 CD4+ epitopes (KGILGFVFTLTVPSE, EYIMKGVYINTALLN, ILGFVFTLTVPSERG). The universal vaccine comprised 8 CD8+ epitopes: (FMYSDFHFI, GILGFVFTL, ILRGSVAHK, FYIQMCTEL, ILKGKFQTA, YYLEKANKI, VSDGGPNLY, YSHGTGTGY) and the same 3 CD4+ epitopes. Our USA-specific vaccine has a population protection coverage (portion of the population potentially responsive to one or more component epitopes of the vaccine, PPC) of over 96% and 95% coverage of observed influenza subtypes. The universal vaccine has a PPC value of over 97% and 88% coverage of observed subtypes.

Pneumonia and influenza: specific considerations in care homes

This review provides an update on current evidence surrounding epidemiology, treatment and prevention of lower respiratory tract infection, with special reference to pneumonia and influenza, in care home residents. The care home sector is growing and provides a unique ecological niche for infections, housing frail older people with multiple comorbidities and frequent contact with healthcare services. There are therefore considerations in the epidemiology and management of these conditions which are specific to care homes. Opportunities for prevention, in the form of vaccination strategies and improving oral hygiene, may reduce the burden of these diseases in the future. Work is needed to research these infections specifically in the care home setting and this article highlights current gaps in our knowledge.

Health, hygiene and biosecurity: tribal knowledge claims in the UK poultry industry

Since 1997 the world has been facing the threat of a human influenza pandemic that may be caused by an avian virus and the poultry industry around the globe has been grappling with the highly pathogenic strain of avian influenza H5N1, or in more informal terms bird flu. The UK poultry industry has lived with and through this threat and its consequences since 2005. This study investigates knowledge claims about health, hygiene and biosecurity as tools to ward off the threat from this virus. It takes a semi-ethnographic and discourse analytic approach to analyse a small corpus of semi-structured interviews carried out in the wake of one of the most publicised outbreaks of H5N1 in Suffolk in 2007. It reveals that claims about what best to do to protect flocks against the risk of disease are divided along lines imposed on the one hand by the structure of the industry and on the other by more 'tribal' lines drawn by knowledge and belief systems about purity and dirt, health and hygiene.

Evaluation of influenza vaccination services and users’ perception about its utility: a study in a community pharmacy in Lisbon, Portugal

Poster presented at the 25th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID). Copenhagen, Denmark, 25–28 April 2015

Fear of the unknown: Inlfuenza vaccination

Influenza is a major cause of morbidity and mortality; current estimates by the World Health Organization (WHO) are 3 to 5 million cases and 250,000 to 500,000 deaths worldwide every year. Most deaths associated with it occur among people age 65 or older, as well as among persons suffering a chronic debilitating disease regardless of age. The recent 2009 pandemic served to foster interest in this disease. An inactivated virus vaccine has been available since the late 1940´s but it only began to be used extensively when the influenza virus antigenic variability was taken into account. Aside from such variability, influenza viruses are capable of infecting a wide variety of vertebrates, including many avian species, both wild and domestic, thus it is essential to monitor the antigenic characteristics of influenza virus strains currently circulating, and so the vaccine formula has to be evaluated and modiied accordingly every year

Valutazione dell'influenza della segnaletica temporanea di cantiere sulla sicurezza stradale mediante Mobile Eye Detector

Analisi sperimentale svolta per valutare come la segnaletica di cantiere, se percepita correttamente, influenza la guida degli utenti che circolano sulla strada interessata da lavorazioni di tipo cantieristico. L'analisi si prefigge anche lo scopo di trovare le soluzioni necessarie per garantire il livello di sicurezza più alto possibile sia per gli utenti che si ritrovano a stretto contatto con il cantiere, che per lavoratori che vi operano.

Il passaggio dalla Business Intelligence all'Advanced Analytics: individuazione e analisi di un modello in merito all'influenza del lobbying nel sistema economico

I Big Data stanno guidando una rivoluzione globale. In tutti i settori, pubblici o privati, e le industrie quali Vendita al dettaglio, Sanità, Media e Trasporti, i Big Data stanno influenzando la vita di miliardi di persone. L’impatto dei Big Data è sostanziale, ma così discreto da passare inosservato alla maggior parte delle persone. Le applicazioni di Business Intelligence e Advanced Analytics vogliono studiare e trarre informazioni dai Big Data. Si studia il passaggio dalla prima alla seconda, mettendo in evidenza aspetti simili e differenze.

Multiresistant Salmonella enterica serovar 4,[5],12:i:- in Europe: a new pandemic strain?

A marked increase in the prevalence of S. enterica serovar 4,[5],12:i:- with resistance to ampicillin, streptomycin, sulphonamides and tetracyclines (R-type ASSuT) has been noted in food-borne infections and in pigs/pig meat in several European countries in the last ten years. One hundred and sixteen strains of S. enterica serovar 4,[5],12:i:- from humans, pigs and pig meat isolated in England and Wales, France, Germany, Italy, Poland, Spain and the Netherlands were further subtyped by phage typing, pulsed-field gel electrophoresis and multilocus variable number tandem repeat analysis to investigate the genetic relationship among strains. PCR was performed to identify the fljB flagellar gene and the genes encoding resistance to ampicillin, streptomycin, sulphonamides and tetracyclines. Class 1 and 2 integrase genes were also sought. Results indicate that genetically related serovar 4,[5],12:i:- strains of definitive phage types DT193 and DT120 with ampicillin, streptomycin, sulphonamide and tetracycline resistance encoded by blaTEM, strA-strB, sul2 and tet(B) have emerged in several European countries, with pigs the likely reservoir of infection. Control measures are urgently needed to reduce spread of infection to humans via the food chain and thereby prevent the possible pandemic spread of serovar 4,[5],12:i:- of R-type ASSuT as occurred with S. Typhimurium DT104 during the 1990s.

Clustering of Rab11 vesicles in influenza A virus infected cells creates hotspots containing the 8 viral ribonucleoproteins

Influenza A virus is an important human pathogen causative of yearly epidemics and occasional pandemics. The ability to replicate within the host cell is a determinant of virulence, amplifying viral numbers for host-to-host transmission. This process requires multiple rounds of entering permissive cells, replication, and virion assembly at the plasma membrane, the site of viral budding and release. The assembly of influenza A virus involves packaging of several viral (and host) proteins and of a segmented genome, composed of 8 distinct RNAs in the form of viral ribonucleoproteins (vRNPs). The selective assembly of the 8-segment core remains one of the most interesting unresolved problems in virology. The recycling endosome regulatory GTPase Rab11 was shown to contribute to the process, by transporting vRNPs to the periphery, giving rise to enlarged cytosolic puncta rich in Rab11 and the 8 vRNPs. We recently reported that vRNP hotspots were formed of clustered vesicles harbouring protruding electron-dense structures that resembled vRNPs. Mechanistically, vRNP hotspots were formed as vRNPs outcompeted the cognate effectors of Rab11, the Rab11-Family-Interacting-Proteins (FIPs) for binding, and as a consequence impair recycling sorting at an unknown step. Here, we speculate on the impact that such impairment might have in host immunity, membrane architecture and viral assembly.

Influenza del vento sulla composizione delle uve

La rilevanza del vento come fattore chiave del terroir, in grado di influenzare la composizione delle uve e del vino, è stata sorprendentemente trascurata. Il lavoro di Tesi ha studiato, per la prima volta, l’influenza del vento sulla composizione delle bacche discutendone i possibili meccanismi d’azione sulla composizione aminoacidica e le conseguenti implicazioni enologiche. È stato valutato l’effetto su viti, della cv Sangiovese, del vento artificiale e della riduzione del vento rispetto un controllo caratterizzato dal vento naturale. Le prove sono state condotte in un vigneto situato a Pesaro a pochi chilometri dal Mare Adriatico, nel quale è stata effettuata una caratterizzazione dei venti e delle brezze. Sulle viti sono stati analizzati i parametri produttivi mentre sulle bacche campionate sono state effettuate le analisi dei principali parametri tecnologici e dei composti azotati (aminoacidi, ammine e ammonio). Le viti sottoposte al vento artificiale hanno manifestato un aumento della concentrazione dei composti azotati totali (aminoacidi e ammonio) rispetto al controllo. In particolare, i cambiamenti hanno coinvolto la concentrazione degli aminoacidi essenziali: lisina, treonina, triptofano, valina, leucina, isoleucina importanti per la loro implicazione nei processi fisiologici. Sulla base dei risultati ottenuti con il lavoro di Tesi e delle informazioni riportate in bibliografia è stato proposto un modello che illustra la possibile azione del vento sulla traslocazione di aminoacidi verso i grappoli. Il vento, oltre al noto effetto positivo sul microclima, ha prodotto un’incredibile influenza sulle bacche con rilevanti implicazioni agronomiche ed enologiche, quest’ultime correlate positivamente al processo fermentativo, alla possibilità di ridurre l’utilizzo di coadiuvanti enologici ed alla qualità dei vini ottenuti.

Studio dell'influenza dell'Adaptive Cruise Control sul carico di lavoro e sulla condotta di guida degli utenti

Il presente elaborato intende valutare l’influenza che i sistemi di assistenza alla guida (ADAS) hanno sul comportamento dei conducenti, con particolare attenzione alla distrazione ed al workload (carico di lavoro fisico e mentale) che essi provocano. Lo studio si concentrerà in particolare sull’analisi del comportamento di guida dei conducenti a bordo di un veicolo dotato di Adaptive Cruise Control.