Future research directions in pneumonia

Copyright © 2018 by the American Thoracic Society. Pneumonia is a complex pulmonary disease in need of new clinical approaches. Although triggered by a pathogen, pneumonia often results from dysregulations of host defense that likely precede infection. The coordinated activities of immune resistance and tissue resilience then dictate whether and how pneumonia progresses or resolves. Inadequate or inappropriate host responses lead to more severe outcomes such as acute respiratory distress syndrome and to organ dysfunction beyond the lungs and over extended time frames after pathogen clearance, some of which increase the risk for subsequent pneumonia. Improved understanding of such host responses will guide the development of novel approaches for preventing and curing pneumonia and for mitigating the subsequent pulmonary and extrapulmonary complications of pneumonia. The NHLBI assembled a working group of extramural investigators to prioritize avenues of host-directed pneumonia research that should yield novel approaches for interrupting the cycle of unhealthy decline caused by pneumonia. This report summarizes the working group’s specific recommendations in the areas of pneumonia susceptibility, host response, and consequences. Overarching goals include the development of more host-focused clinical approaches for preventing and treating pneumonia, the generation of predictive tools (for pneumonia occurrence, severity, and outcome), and the elucidation of mechanisms mediating immune resistance and tissue resilience in the lung. Specific areas of research are highlighted as especially promising for making advances against pneumonia

Human papillomavirus 16 is an aetiological factor of scrotal cancer

Background: Squamous cell scrotal carcinoma (SCSC) is an infrequent skin cancer associated historically with occupational carcinogens. Human papillomavirus (HPV) DNA has been associated with SCSC but there is no definitive proof of its oncogenic role. Methods: Human papillomavirus-DNA and -E6*I mRNA were analysed in six invasive histologically typed SCSC. LCM-PCR was used to localise HPV DNA to tumour cells. P16(INK4a)and p53 expression were studied by immunohistochemistry. Results: In three warty or basaloid SCSC HPV16-DNA and E6*I-mRNA were detected. LCM-PCR confirmed HPV16 was in p16(INK4a)-positive malignant cells. However, of three usual-type SCSC, all were HPV-negative and two expressed p53 protein but not p16(INK4a). Conclusions: Human papillomavirus 16 was present in tumour cells and oncogenically active in basaloid and warty SCSC, whereas usual SCSC was HPV-negative and showed immunostaining, suggesting p53 mutation. The dual pathways of oncogenesis and relation between histological type of SCSC and HPV are similar to that in penile cancers

Monitoring the Long-Term Molecular Epidemiology of the Pneumococcus and Detection of Potential ‘Vaccine Escape’ Strains

While the pneumococcal protein conjugate vaccines reduce the incidence in invasive pneumococcal disease (IPD), serotype replacement remains a major concern. Thus, serotype-independent protection with vaccines targeting virulence genes, such as PspA, have been pursued. PspA is comprised of diverse clades that arose through recombination. Therefore, multi-locus sequence typing (MLST)-defined clones could conceivably include strains from multiple PspA clades. As a result, a method is needed which can both monitor the long-term epidemiology of the pneumococcus among a large number of isolates, and analyze vaccine-candidate genes, such as pspA, for mutations and recombination events that could result in 'vaccine escape' strains.We developed a resequencing array consisting of five conserved and six variable genes to characterize 72 pneumococcal strains. The phylogenetic analysis of the 11 concatenated genes was performed with the MrBayes program, the single nucleotide polymorphism (SNP) analysis with the DNA Sequence Polymorphism program (DnaSP), and the recombination event analysis with the recombination detection package (RDP).The phylogenetic analysis correlated with MLST, and identified clonal strains with unique PspA clades. The DnaSP analysis correlated with the serotype-specific diversity detected using MLST. Serotypes associated with more than one ST complex had a larger degree of sequence polymorphism than a serotype associated with one ST complex. The RDP analysis confirmed the high frequency of recombination events in the pspA gene.The phylogenetic tree correlated with MLST, and detected multiple PspA clades among clonal strains. The genetic diversity of the strains and the frequency of recombination events in the mosaic gene, pspA were accurately assessed using the DnaSP and RDP programs, respectively. These data provide proof-of-concept that resequencing arrays could play an important role within research and clinical laboratories in both monitoring the molecular epidemiology of the pneumococcus and detecting 'vaccine escape' strains among vaccine-candidate genes

Streptococcus pneumoniae Clonal Complex 199: Genetic Diversity and Tissue-Specific Virulence

Streptococcus pneumoniae is an important cause of otitis media and invasive disease. Since introduction of the heptavalent pneumococcal conjugate vaccine, there has been an increase in replacement disease due to serotype 19A clonal complex (CC)199 isolates. The goals of this study were to 1) describe genetic diversity among nineteen CC199 isolates from carriage, middle ear, blood, and cerebrospinal fluid, 2) compare CC199 19A (n = 3) and 15B/C (n = 2) isolates in the chinchilla model for pneumococcal disease, and 3) identify accessory genes associated with tissue-specific disease among a larger collection of S. pneumoniae isolates. CC199 isolates were analyzed by comparative genome hybridization. One hundred and twenty-seven genes were variably present. The CC199 phylogeny split into two main clades, one comprised predominantly of carriage isolates and another of disease isolates. Ability to colonize and cause disease did not differ by serotype in the chinchilla model. However, isolates from the disease clade were associated with faster time to bacteremia compared to carriage clade isolates. One 19A isolate exhibited hypervirulence. Twelve tissue-specific genes/regions were identified by correspondence analysis. After screening a diverse collection of 326 isolates, spr0282 was associated with carriage. Four genes/regions, SP0163, SP0463, SPN05002 and RD8a were associated with middle ear isolates. SPN05002 also associated with blood and CSF, while RD8a associated with blood isolates. The hypervirulent isolate's genome was sequenced using the Solexa paired-end sequencing platform and compared to that of a reference serotype 19A isolate, revealing the presence of a novel 20 kb region with sequence similarity to bacteriophage genes. Genetic factors other than serotype may modulate virulence potential in CC199. These studies have implications for the long-term effectiveness of conjugate vaccines. Ideally, future vaccines would target common proteins to effectively reduce carriage and disease in the vaccinated population

On realcompact topological vector spaces

[EN] This survey paper collects some of older and quite new concepts and results from descriptive set topology applied to study certain infinite-dimensional topological vector spaces appearing in Functional Analysis, including Frechet spaces, (L F)-spaces, and their duals, (D F)-spaces and spaces of continuous real-valued functions C(X) on a completely regular Hausdorff space X. Especially (L F)-spaces and their duals arise in many fields of Functional Analysis and its applications, for example in Distributions Theory, Differential Equations and Complex Analysis. The concept of a realcompact topological space, although originally introduced and studied in General Topology, has been also studied because of very concrete applications in Linear Functional Analysis.The research for the first named author was (partially) supported by Ministry of Science and Higher Education, Poland, Grant no. 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Estimación de la intensidad sísmica en Caracas durante el terremoto de 1812, utilizando metodología de microzonificación.

SUMARIO / SUMMARY 1.- Editorial Las Cuartas Jornadas Venezolanas de Sismología Histórica y Quinto Simposio Venezolano de Historia de las Geociencias. Trujillo, 28-30 de octubre de 2004. The Fourth Workshop in Historical Seismology and Fifth Venezuelan Symposium of Geosciences History. Trujillo, 28-30 October, 2004. Altéz, Rogelio; Ferrer Oropeza, Carlos y Laffaille, Jaime R. 2.- Artículos / Papers La legitimidad del riesgo y la construcción social del desastre. The legitimacy of risk and the disaster social construction. Klein, Emma Contar los muertos para contar la muerte: discusión en torno al número de fallecidos en la tragedia de 1999 en el estado Vargas-Venezuela. Counting the deseases to tell the death: discussion about the number of deaths in Vargas'99 tragedy, Vargas state-Venezuela. Altéz, Rogelio y Revet, Sandrine Depósitos cuaternarios de la cordillera Central entre Calarcá y Pijao (Quindío-Colombia): evidencia de actividad tectónica reciente. Cordillera Central's quaternary deposits between Calarcá and Pijao (Quindío-Colombia): an evidence of recent tectonic activity. Botero, Paola; García, Luisa; Hernández, Catalina; Sepúlveda, Leonardo y Torres, Eliana Evaluación de la actividad tectónica reciente del frente montañoso occidental de la cordillera Central entre Calarcá y Pijao (Quindío-Colombia). Evaluation of the recent tectonic activity in the west mountain front of cordillera Central between Calarcá and Pijao (Quindío-Colombia). Botero, Paola; García, Luisa; Hernández, Catalina; Sepúlveda, Leonardo y Torres, Eliana Evidencias de la formación y ruptura de una presa natural en la cuenca media del río Chama (Andes centrales venezolanos): limitaciones de los catálogos históricos. An evidence about the formation and rupture of a natural dam in the middle basin of the Chama River (venezuelan central Andes): the limitations of historical catalogues. Ferrer Oropeza, Carlos; Laffaille, Jaime R. y Rincón, Juan C. Un estudio de amenazas múltiples en la cuenca media del río Chama (Andes centrales venezolanos): caso zanjón El Paraíso. A study about multiple hazards in the basin of the Chama River (Venezuelan central Andes): the case of El Paraiso torrent. Ferrer Oropeza, Carlos y Laffaille, Jaime R. Las furias del temblor. Análisis comparativo de dos sismos históricos: Quito, febrero 1797 y Cumaná, diciembre 1797. Comparative analysis of two historical earthquakes: Quito, February 1797 and Cumana, December 1797. Amodio, Emanuele Todo lo que se movió en 1812 en la placa del Caribe: sismos, volcanes y transmisión de energía. Everything that moved in 1812 in the Caribbean plate: earthquakes, vulcan, and stress transfer. Altéz, Rogelio El terremoto de 1812 en la ciudad de Caracas: un intento de microzonificación histórica. The 1812 earthquake in Caracas city: an historic microzoning attempt. Altéz, Rogelio Estimation of the seismic intensity in Caracas during 1812 earthquake using seismic microzonation methodology. Estimación de la intensidad sísmica en Caracas durante el terremoto de 1812, utilizando metodología de microzonificación. Yamazaki, Yoshitaka; Audemard M., Franck A.; Altéz, Rogelio; Hernández, Julio; Orihuela, Nuris; Safina, Salvador; Schmitz, Michael; Tanaka, Ichiro y Kagawa, H. El terremoto de Mérida de 1812: escudriñando entre las páginas de una novela inconclusa en busca de información acerca de una historia real. The 1812 Merida earthquake: investigating through the pages of an unfinished novel in search of information about a real story. Laffaille, Jaime R. y Ferrer Oropeza, Carlos Re-evaluación de las intensidades de los grandes sismos históricos de la región de la cordillera de Mérida utilizando el método de Bakun & Wentworth. Cordillera de Merida region great historical earthquakes intensity reevaluation using the Bakun & Wentworth method. Palme, Christl; Morandi S., María T. y Choy, José E. 3.- Notas y Documentos / Notes and Documents Algunas contribuciones de Günther Fieldler a la sismología venezolana Contributions by Günther Fiedler to venezuelan seismology. Grases, José Alejandro de Humboldt, 1799-1800. El primer geólogo en Venezuela. Alexander von Humboldt, 1799-1800. The first geologist in Venezuela. Urbani, Franco El consumidero del río Guaire, Miranda Venezuela: un caso histórico de obstrucción de una cueva. The consumidero of Guaire River, Miranda State - Venezuela: a cave obstruction historical case. Urbani, Franco Antecedentes históricos de eventos meteorológicos ocurridos en el valle del río Mocotíes y sus impactos geomorfológicos. Historical background of the meteorological events occurred in the Mocotíes River valley and their geomorphic impact. Laffaille, Jaime R.; Ferrer Oropeza, Carlos y Rincón, Juan C. Historia sin memoria: la cotidiana recurrencia de eventos desastrosos en el estado Vargas - Venezuela. History without memory: the quotidian recurrence of disastrous events in Vargas State - Venezuela. Altéz, Rogelio 4.- Bibliografía Crítica / Books Review Altez, Rogelio; Rodríguez, José A. Y Urbani, Franco: Historia del pensamiento sismológico en Venezuela... una mirada inquieta Altez, Rogelio; Rodríguez, José A. Y Urbani, Franco: History of seismologic thought in Venezuela... a restless glance. Reseñado por: Trinca Fighera, [email protected]@[email protected]@[email protected]@[email protected]@[email protected] analíticosemestra

Noradrenaline-Functionalized Hyperbranched Fluoropolymer–Poly(ethylene glycol) Cross-Linked Networks As Dual-Mode, Anti-Biofouling Coatings

The strategy of decorating antibiofouling hyperbranched fluoropolymer–poly(ethylene glycol) (HBFP-PEG) networks with a settlement sensory deterrent, noradrenaline (NA), and the results of biofouling assays are presented. This example of a dual-mode surface, which combines both passive and active modes of antibiofouling, works in synergy to improve the overall antibiofouling efficiency against barnacle cyprids. The HBFP-PEG polymer surface, prior to modification with NA, was analyzed by atomic force microscopy, and a significant distribution of topographical features was observed, with a nanoscopic roughness measurement of 110 ± 8 nm. NA attachment to the surface was probed by secondary ion mass spectrometry to quantify the extent of polymer chain-end substitution with NA, where a 3- to 4-fold increase in intensity for a fragment ion associated with NA was observed and 39% of the available sites for attachment were substituted. Cytoskeletal assays confirmed the activity of tethered NA on adhering oyster hemocytes. Settlement assays showed deterrence toward barnacle cyprid settlement, while not compromising the passive biofouling resistance of the surface. This robust strategy demonstrates a methodology for the incorporation of actively antibiofouling moieties onto a passively antibiofouling network