Neuroinvasion of the Highly Pathogenic Influenza Virus H7N1 Is Caused by Disruption of the Blood Brain Barrier in an Avian Model

Influenza A virus (IAV) causes central nervous system (CNS) lesions in avian and mammalian species, including humans. However, the mechanism used by IAV to invade the brain has not been determined. In the current work, we used chickens infected with a highly pathogenic avian influenza (HPAI) virus as a model to elucidate the mechanism of entry of IAV into the brain. The permeability of the BBB was evaluated in fifteen-day-old H7N1-infected and non-infected chickens using three different methods: (i) detecting Evans blue (EB) extravasation into the brain, (ii) determining the leakage of the serum protein immunoglobulin Y (IgY) into the brain and (iii) assessing the stability of the tight-junction (TJ) proteins zonula occludens-1 and claudin-1 in the chicken brain at 6, 12, 18, 24, 36 and 48 hours post-inoculation (hpi). The onset of the induced viremia was evaluated by quantitative real time RT-PCR (RT-qPCR) at the same time points. Viral RNA was detected from 18 hpi onward in blood samples, whereas IAV antigen was detected at 24 hpi in brain tissue samples. EB and IgY extravasation and loss of integrity of the TJs associated with the presence of viral antigen was first observed at 36 and 48 hpi in the telencephalic pallium and cerebellum. Our data suggest that the mechanism of entry of the H7N1 HPAI into the brain includes infection of the endothelial cells at early stages (24 hpi) with subsequent disruption of the TJs of the BBB and leakage of virus and serum proteins into the adjacent neuroparenchyma

Pathobiology and transmission of highly and low pathogenic avian influenza viruses in European quail (Coturnix c. coturnix)

European quail (Coturnix c. coturnix) may share with Japanese quail (Coturnix c. japonica) its potential as an intermediate host and reservoir of avian influenza viruses (AIV). To elucidate this question, European quail were experimentally challenged with two highly pathogenic AIV (HPAIV) (H7N1/HP and H5N1/HP) and one low pathogenic AIV (LPAIV) (H7N2/LP). Contact animals were also used to assess the viral transmission among birds. Severe neurological signs and mortality rates of 67% (H7N1/HP) and 92% (H5N1/HP) were observed. Although histopathological findings were present in both HPAIV-infected groups, H5N1/HP-quail displayed a broader viral antigen distribution and extent of microscopic lesions. Neither clinical nor pathological involvement was observed in LPAIV-infected quail. Consistent long-term viral shedding and effective transmission to naive quail was demonstrated for the three studied AIV. Drinking water arose as a possible transmission route and feathers as a potential origin of HPAIV dissemination. The present study demonstrates that European quail may play a major role in AI epidemiology, highlighting the need to further understand its putative role as an intermediate host for avian/mammalian reassortant viruses

Geographical inequalities in energy poverty in a Mediterranean city : Using small-area Bayesian spatial models

Altres ajuts: Ministerio de Economía y Competitividad; European Union, European Regional Development Fund (FEDER); CIBER Epidemiología Salud Pública (CIBERESP), sub-program "Energy Poverty and Health"; Fondo Social Europeo.Energy poverty (EP) is becoming an increasingly important problem in the urban contexts of southern Europe. In Barcelona, EP indicators are higher than those of the European Union and are strongly associated with poor health status and high use of health services and medication, becoming a major public health problem. EP is unevenly distributed in the population of Barcelona, according to axes of social stratification. However, its geographic distribution at the small-area level remains unknown because it cannot be directly estimated with the available information sources and commonly used methods. Therefore, the aim of this study was to analyze geographical inequalities in EP in Barcelona by estimating reliable small-area EP indicators and a composite indicator (index). We used a novel method that allowed us to obtain 6 EP indicators for the 73 Barcelona neighborhoods and an EP index from a principal component analysis of these indicators. We found major geographical inequalities in the distribution of EP in Barcelona. Many neighborhoods had significantly higher EP than the city average, and these areas made up 3 well-defined spatial clusters. Therefore, the estimated small-area indicators and index allowed identification of the most affected neighborhoods. These results indicate the need to prioritize these areas for local interventions to alleviate EP, and could also be used for policy making

Caracterización De Los Segmentos Repetidos Involuntariamente En Habla Semiespontánea. Describing Non-Voluntary Repetition Of Segments In Semispontaneous Speech

RESUMEN En esta investigación se analizan casos de repeticiones involuntarias de segmentos en muestras de habla semiespontánea de un hombre y de una mujer de Santiago de Chile. Las muestras fueron sometidas a un análisis acústico de la duración en el oscilograma y el espectrograma correspondiente. Se presentan los datos desde una perspectiva general (tipos de palabras que aparecen más recurrentemente, número de reiteraciones y número de componentes del segmento repetido) y también se exponen los resultados de un análisis más específico de la duración de los segmentos. Estos resultados muestran que las palabras de clase cerrada tienen mayor frecuencia de aparición, que el segmento tiende a repetirse dos veces y que suele estar constituido por un elemento. El análisis temporal revela con mucha consistencia que el primer segmento es más largo que el segundo. A pesar de la escasa información sobre estos temas en lengua española, es sabido que se trata de fenómenos que tienen directa relación con el procesamiento de la información verbal. ABSTRACT This study is focused on describing the non-voluntary repetition of segments by a man and woman, both Chilean. Each sample´s lenght was determined by means of an acoustic analysis in which both the oscillogram chart and the spectrogram chart were inspected for every sample. The data were gathered from two samples of semi-spontaneous speech and they were approached both from a general descriptive point of view -kind of words more frequently used, number of repetitions, how many items were included in the repeated segments- and from a more specific perspective in which the lengths of the analyzed segments were compared statistically. The results of the analysis showed that function words are more frequently repeated, that segments tend to be repeated twice and that the repeated segment is likely to consist of a single item. The statistical test on the segments’ length clearly showed that the first segment is usually longer than second one. Information about Spanish-language oriented studies approaching similar matters is very little, but nevertheless there seems to be little question about the fact that these phenomena are clearly related with the processing of verbal information

Neurotoxicity of prion peptides mimicking the central domain of the cellular prion protein

The physiological functions of PrP(C) remain enigmatic, but the central domain, comprising highly conserved regions of the protein may play an important role. Indeed, a large number of studies indicate that synthetic peptides containing residues 106-126 (CR) located in the central domain (CD, 95-133) of PrP(C) are neurotoxic. The central domain comprises two chemically distinct subdomains, the charge cluster (CC, 95-110) and a hydrophobic region (HR, 112-133). The aim of the present study was to establish the individual cytotoxicity of CC, HR and CD. Our results show that only the CD peptide is neurotoxic. Biochemical, Transmission Electron Microscopy and Atomic Force Microscopy experiments demonstrated that the CD peptide is able to activate caspase-3 and disrupt the cell membrane, leading to cell death

EVOLUCIÓN DEL CRECIMIENTO Y LA SIMETRÍA CORPORAL EN BÚFALOS DE LA RAZA BUFFALYPSO (BUBALUS BUBALIS) EN BOCAS DEL TORO, REPÚBLICA DE PANAMÁ

The evolution of body growth and symmetric dimensions in the Buffalypso water buffalo (Bubalus bubalis) were evaluated by sex across the first 36 months under a feeding model based on Tanner (Brachiaria arrecta) at annual THI 77.91 ± 1.24 °% in 146 buffaloes in Bocas del Toro Province, Republic of Panama. Body weight and symmetric indexes were different in the first 36 months (P<.001). Body weight in males (61) and females (85) were at 12 months (207.8 and 176 kg, p<.001), 24 (306.6 and 248.1 kg, p<.001) and at 36 months (373.77 and 368.2 kg, p>.05); resulting males heavier than females in 18.04, 23.58 and 1.48%. Those values represented 85 to 89% of the Buffalypso weight pattern. The sectorial body weight gains were highest in the first eight months (males 0.554 kg/day and females 0.530 kg/day, P>.05), 12 to 24 months (males 0.258 and females 0.146 kg/day, P<.01), 24.1 to 30 months (males 0.419 and females 0.468 kg/day, P>.05); and from 30.1 to 36 months (males 0.160 and 0.261 kg/day, P<.01). Body dimensional parameters were positively correlated to body weight and age in both sexes from 0.59 to 0.97 (P<.001). The evolution of body growth according to body weight showed a sigmoidal polinomic shape, but it was below the Buffalypso growth pattern under the feeding model based on Tanner, which indicated the needs for adjustments in nutrition, feeding, health and management to increase the growth rate and productivity of Buffalypso water buffalo in Panamá.La evolución del crecimiento y la simetría corporal fueron evaluadas en los primeros 36 meses de vida en 146 búfalos de la raza Buffalypso (Bubalus bubalis) según el sexo; bajo alimentación con pasto Tanner (Brachiaria arrecta), salvo en los lactantes en el clima tropical húmedo (ITHanual 77.91 ± 1.24) en La Provincia de Bocas del Toro, República de Panamá. El peso y los índices simétricos corporales fueron diferentes en los primeros 36 meses de vida según el sexo (P<.001). Los machos (61) y hembras (85) pesaron a los 12 meses (207.8 y 176 kg; p< .001), 24 (306.6 y 248.1 kg; p< .001) y 36 meses (373.77 y 368.1 kg, p>.05); resultando los machos superiores en 18.04, 23.58 y 1.48% a las hembras; alcanzando entre 85 y 89% del peso racial Buffalypso. Las ganancias de pesos sectoriales fueron: lactantes (bucerros 0.554 y bucerras 0.530 kg/día, P>.05), 12 a 24 meses (machos 0.258 y hembras 0.146 kg/día, P<.01), 24.1 a 30 meses (machos 0.419 y hembras 0.468 g/día, P>.05) y de 30.1 a 36 meses (machos 0.160 y hembras 0.261 kg/día, P<.01). Los índices simétricos corporales estuvieron correlacionados positivamente con la edad en ambos sexos (0.59 a 0.97, P<.0001). La evolución del crecimiento según el peso y la simetría corporal fue sigmoidal polinómica en ambos sexos alimentación con Tanner, pero inferior al peso racial Buffalypso; indicando la necesidad de implementar ajustes en nutrición, alimentación, salud y manejo para incrementar el crecimiento y la productividad del Búfalo de Agua Buffalypso en Panamá

Generating and measuring the anisotropic elastic behaviour of Co thin films with oriented surface nano-strings on micro-cantilevers

In this research, the elastic behaviour of two Co thin films simultaneously deposited in an off-normal angle method was studied. Towards this end, two Si micro-cantilevers were simultaneously coated using pulsed laser deposition at an oblique angle, creating a Co nano-string surface morphology with a predetermined orientation. The selected position of each micro-cantilever during the coating process created longitudinal or transverse nano-strings. The anisotropic elastic behaviour of these Co films was determined by measuring the changes that took place in the resonant frequency of each micro-cantilever after this process of creating differently oriented plasma coatings had been completed. This differential procedure allowed us to determine the difference between the Young's modulus of the different films based on the different direction of the nano-strings. This difference was determined to be, at least, the 20% of the Young's modulus of the bulk Co

Hypoxia compromises the mitochondrial metabolism of Alzheimer’s disease microglia via HIF1

Genetic Alzheimer’s disease (AD) risk factors associate with reduced defensive amyloid β plaque-associated microglia (AβAM), but the contribution of modifiable AD risk factors to microglial dysfunction is unknown. In AD mouse models, we observe concomitant activation of the hypoxia-inducible factor 1 (HIF1) pathway and transcription of mitochondrial-related genes in AβAM, and elongation of mitochondria, a cellular response to maintain aerobic respiration under low nutrient and oxygen conditions. Overactivation of HIF1 induces microglial quiescence in cellulo, with lower mitochondrial respiration and proliferation. In vivo, overstabilization of HIF1, either genetically or by exposure to systemic hypoxia, reduces AβAM clustering and proliferation and increases Aβ neuropathology. In the human AD hippocampus, upregulation of HIF1α and HIF1 target genes correlates with reduced Aβ plaque microglial coverage and an increase of Aβ plaque-associated neuropathology. Thus, hypoxia (a modifiable AD risk factor) hijacks microglial mitochondrial metabolism and converges with genetic susceptibility to cause AD microglial dysfunction.Instituto de Salud Carlos III CD09/0007, PI18/01556, PI18/01557Ministerio de Educación, Cultura y Deporte FPU14/02115, AP2010‐1598, FPU16/02050, FPU15/02898, BES-2010-033886Ministerio de Economia, Industria y Competitividad SAF2012‐33816, SAF2015‐64111‐R, SAF2017-90794-REDT, PIE13/0004, BFU2016-76872-R, BES-2011-047721Junta de Andalucía P12‐CTS‐2138, P12‐CTS‐2232, UMA18-FEDERJA-211, US‐126273

Procalcitonin (PCT) levels for ruling-out bacterial coinfection in ICU patients with influenza: A CHAID decision-tree analysis

Objectives: To define which variables upon ICU admission could be related to the presence of coinfection using CHAID (Chi-squared Automatic Interaction Detection) analysis. Methods: A secondary analysis from a prospective, multicentre, observational study (2009-2014) in ICU patients with confirmed A(H1N1)pdm09 infection. We assessed the potential of biomarkers and clinical variables upon admission to the ICU for coinfection diagnosis using CHAID analysis. Performance of cut-off points obtained was determined on the basis of the binominal distributions of the true (+) and true (−) results. Results: Of the 972 patients included, 196 (20.3%) had coinfection. Procalcitonin (PCT; ng/mL 2.4 vs. 0.5, p < 0.001), but not C-reactive protein (CRP; mg/dL 25 vs. 38.5; p = 0.62) was higher in patients with coinfection. In CHAID analyses, PCT was the most important variable for coinfection. PCT <0.29 ng/mL showed high sensitivity (Se = 88.2%), low Sp (33.2%) and high negative predictive value (NPV = 91.9%). The absence of shock improved classification capacity. Thus, for PCT <0.29 ng/mL, the Se was 84%, the Sp 43% and an NPV of 94% with a post-test probability of coinfection of only 6%. Conclusion: PCT has a high negative predictive value (94%) and lower PCT levels seems to be a good tool for excluding coinfection, particularly for patients without shock