Validation of Immunoassay-Based Tools for the Comprehensive Quantification of Aß40 and Aß42 Peptides in Plasma

Recent advances in neuroimaging and cerebrospinal fluid (CSF) biomarker assays have provided evidence of a long preclinical stage of Alzheimer''s disease (AD). This period is being increasingly targeted for secondary prevention trials of new therapies. In this context, the interest of a noninvasive, cost-effective amyloid-ß (Aß) blood-based test does not need to be overstated. Nevertheless, a thorough validation of these bioanalytical methods should be performed as a prerequisite for confident interpretation of clinical results. The aim of this study was to validate ELISA sandwich colorimetric ABtest40 and ABtest42 for the quantification of Aß40 and Aß42 in human plasma. The validation parameters assessed included precision, accuracy, sensitivity, specificity, recovery, and dilution linearity. ABtest40 and ABtest42 proved to be specific for their target peptide using Aß peptides with sequence similar to the target. Mean relative error in the quantification was found to be below 7.5 for both assays, with high intra-assay, inter-assay, and inter-batch precision (CV <9.0 on average). Sensitivity was assessed by determination of the limit of quantification fulfilling precision and accuracy criteria; it was established at 7.60 pg/ml and 3.60 pg/ml for ABtest40 and ABtest42, respectively. Plasma dilution linearity was demonstrated in PBS; however, dilution in a proprietary formulated buffer significantly increased the recovery of both Aß40 and Aß42 masked by matrix interactions, allowing a more comprehensive assessment of the free and total peptide levels in the plasma. In conclusion, both assays were successfully validated as tools for the quantification Aß40 and Aß42 in plasma

Characterization of pre-analytical sample handling effects on a panel of Alzheimer's disease–related blood-based biomarkers: Results from the Standardization of Alzheimer's Blood Biomarkers (SABB) working group

Introduction: Pre-analytical sample handling might affect the results of Alzheimer's disease blood-based biomarkers. We empirically tested variations of common blood collection and handling procedures. Methods: We created sample sets that address the effect of blood collection tube type, and of ethylene diamine tetraacetic acid plasma delayed centrifugation, centrifugation temperature, aliquot volume, delayed storage, and freeze–thawing. We measured amyloid beta (Aβ)42 and 40 peptides with six assays, and Aβ oligomerization-tendency (OAβ), amyloid precursor protein (APP)699-711, glial fibrillary acidic protein (GFAP), neurofilament light (NfL), total tau (t-tau), and phosphorylated tau181. Results: Collection tube type resulted in different values of all assessed markers. Delayed plasma centrifugation and storage affected Aβ and t-tau; t-tau was additionally affected by centrifugation temperature. The other markers were resistant to handling variations. Discussion: We constructed a standardized operating procedure for plasma handling, to facilitate introduction of blood-based biomarkers into the research and clinical settings

Evidence for phenotypic plasticity but not for compensatory horn growth in male Iberian ibex

The description of horn growth patterns is of utmost importance for the sustainable management of wild ungulate populations subjected to intense trophy hunting. This is a topic of renewed interest because horn growth patterns seem to be contingent on region and population. We sampled 2145 male Iberian ibexes (Capra pyrenaica) evenly distributed across the Els Ports de Tortosa i Beseit National Game Reserve, NE Spain. A total of 24,615 annual horn growth segments were measured and used to describe horn growth patterns of male ibexes and to test whether compensatory horn growth occurs in an heterogeneous area. We found that individual heterogeneity explained more than a quarter (27.75%) of the variability in annual segment length and that habitat characteristics foster significant phenotypic differences among male ibexes. Our results corroborate previous studies by demonstrating that compensatory horn growth in male ibexes, as in other members of the tribe Caprini, is inexistent. Our study goes one step further and suggests that compensatory horn growth in male ibexes is neither promoted by cohort effects nor by habitat differences. The absence of compensatory horn growth has important management implications, namely: (i) male ibexes are not able to recover from a bad start, and (ii) the species is prone to evolutionary effects from trophy hunting. We emphasize that the study of just one proxy of horn growth may hamper the current knowledge about compensatory mechanisms in wild ungulates and imperil the development of effective management measures

The global Alzheimer's Association round robin study on plasma amyloid β methods

Introduction: Blood-based assays to measure brain amyloid beta (Aβ) deposition are an attractive alternative to the cerebrospinal fluid (CSF)-based assays currently used in clinical settings. In this study, we examined different blood-based assays to measure Aβ and how they compare among centers and assays. Methods: Aliquots from 81 plasma samples were distributed to 10 participating centers. Seven immunological assays and four mass-spectrometric methods were used to measure plasma Aβ concentrations. Results: Correlations were weak for Aβ42 while Aβ40 correlations were stronger. The ratio Aβ42/Aβ40 did not improve the correlations and showed weak correlations. Discussion: The poor correlations for Aβ42 in plasma might have several potential explanations, such as the high levels of plasma proteins (compared to CSF), sensitivity to pre-analytical sample handling and specificity, and cross-reactivity of different antibodies. Different methods might also measure different pools of plasma Aβ42. We, however, hypothesize that greater correlations might be seen in future studies because many of the methods have been refined during completion of this study

Inflammatory response in mixed viral-bacterial community-acquired pneumonia

BACKGROUND: The role of mixed pneumonia (virus + bacteria) in community-acquired pneumonia (CAP) has been described in recent years. However, it is not known whether the systemic inflammatory profile is different compared to monomicrobial CAP. We wanted to investigate this profile of mixed viral-bacterial infection and to compare it to monomicrobial bacterial or viral CAP. METHODS: We measured baseline serum procalcitonin (PCT), C reactive protein (CRP), and white blood cell (WBC) count in 171 patients with CAP with definite etiology admitted to a tertiary hospital: 59 (34.5%) bacterial, 66 (39.%) viral and 46 (27%) mixed (viral-bacterial). RESULTS: Serum PCT levels were higher in mixed and bacterial CAP compared to viral CAP. CRP levels were higher in mixed CAP compared to the other groups. CRP was independently associated with mixed CAP. CRP levels below 26 mg/dL were indicative of an etiology other than mixed in 83% of cases, but the positive predictive value was 45%. PCT levels over 2.10 ng/mL had a positive predictive value for bacterial-involved CAP versus viral CAP of 78%, but the negative predictive value was 48%. CONCLUSIONS: Mixed CAP has a different inflammatory pattern compared to bacterial or viral CAP. High CRP levels may be useful for clinicians to suspect mixed CAP

Effect of Ultrasonic-Assisted Blanching on Size Variation, Heat Transfer, and Quality Parameters of Mushrooms

The main aim of this work was to assess the influence of the application of power ultrasound during blanching of mushrooms (60 90 °C) on the shrinkage, heat transfer, and quality parameters. Kinetics of mushroom shrinkage was modeled and coupled to a heat transfer model for conventional (CB) and ultrasonic-assisted blanching (UB). Cooking value and the integrated residual enzymatic activity were obtained through predicted temperatures and related to the hardness and color variations of mushrooms, respectively. The application of ultrasound led to an increase of shrinkage and heat transfer rates, being this increase more intense at low process temperatures. Consequently, processing time was decreased (30.7 46.0 %) and a reduction in hardness (25.2 40.8 %) and lightness (13.8 16.8 %) losses were obtained. The best retention of hardness was obtained by the UB at 60 °C, while to maintain the lightness it was the CB and UB at 90 °C. For enhancing both quality parameters simultaneously, a combined treatment (CT), which consisted of a CB 0.5 min at 90 °C and then an UB 19.9min at 60 °C, was designed. In this manner, compared with the conventional treatment at 60 °C, reductions of 39.1, 27.2, and 65.5 % for the process time, hardness and lightness losses were achieved, respectively. These results suggest that the CT could be considered as an interesting alternative to CB in order to reduce the processing time and improve the overall quality of blanched mushrooms.The authors acknowledge the financial support of Consejo Nacional de Investigaciones Cientificas y Tecnicas and Universidad Nacional de La Plata from Argentina, Erasmus Mundus Action 2-Strand 1 and EuroTango II Researcher Training Program and Ministerio de Economia y Competitividad (SPAIN) and the FEDER (project DPI2012-37466-CO3-03).Lespinard, A.; Bon Corbín, J.; Cárcel Carrión, JA.; Benedito Fort, JJ.; Mascheroni, RH. (2015). 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Comparative Analysis of American and Spanish Cruise Passenger's Behavioral Intentions

[EN] Earlier studies of cross-national differences in consumer behavior in different consumption sectors have verified that cultural differences have a strong influence on consumers. Despite the importance of cross-national analysis, no studies in the literature examine the moderating effects of nationality on the construction of behavioral intentions and their antecedents among cruise line passengers. This study investigates the moderating effects of nationality on the relationships between perceived value, satisfaction, trust and behavioral intentions among Spanish and (U.S.) American passengers of cruise lines that use Barcelona as home port and port-of-call. A theoretical model was tested with a total of 968 surveys. Structural equation models (SEMs) were used, by means of a multigroup analysis. Results of this study indicated that Spaniards showed stronger relationships between trust and behavioral intentions, and between emotional value and satisfaction. Americans presented stronger relations.[PT] Estudos em distintos setores de consumo verificaram que as diferenças culturais têm uma forte influência sobre os consumidores. Apesar da importância da análise transnacional, não há estudos na literatura que examinem os efeitos da nacionalidade na construção das intenções de comportamento e seus antecedentes entre os passageiros de cruzeiros. Esta pesquisa investiga os efeitos moderadores da nacionalidade nas relações entre valor percebido, satisfação, confiança e intenções de comportamento entre passageiros espanhóis e norte-americanos. Realizaram-se 968 enquetes para provar o modelo teórico, que foi analisado com modelos de equações estruturais, mediante uma análise multigrupo. Os resultados indicam que os espanhóis mostraram relações mais fortes entre confiança e intenções de comportamento, e entre valor emocional e satisfação. Ao contrário dos norte-americanos, que apresentaram relações mais fortes entre qualidade de serviço e satisfação, e entre qualidade de serviço e intenções de comportamento.[ES] Algunos estudios anteriores de diferencias observadas entre países respecto de las conductas de los consumidores de diferentes sectores de consumo verificaron que las diferencias culturales ejercen una poderosa influencia sobre los consumidores. A pesar de la importancia de los análisis transnacionales, no hay en la literatura estudios que analicen los efectos moderadores de la nacionalidad sobre la construcción de intenciones de conducta y sus antecedentes entre pasajeros de cruceros. Este estudio investiga los efectos moderadores de la nacionalidad sobre las relaciones entre el valor percibido, la satisfacción, la confianza y las intenciones de conducta entre los pasajeros españoles y norteamericanos (EE. UU.) de cruceros, que utilizan a Barcelona como puerto de origen y puerto de escala. Se probó un modelo teórico con un total de 968 encuestas. Se emplearon modelos de ecuaciones estructurales (SEM por su sigla en inglés), a través de un análisis multigrupo. Los resultados de este estudio indicaron que los españoles mostraron relaciones más sólidas entre la confianza y las intenciones de comportamiento y entre el valor emocional y la satisfacción. Los americanos evidenciaron relaciones más sólidas entre la calidad del servicio y la satisfacción y entre la calidad del servicio y las intenciones de conducta.Forgas-Coll, S.; Palau-Saumell, R.; Sanchez-Garcia, J.; Garrigós Simón, FJ. (2016). Comparative Analysis of American and Spanish Cruise Passenger's Behavioral Intentions. RAE-Revista de Administração de Empresas. 56(1):87-100. doi:10.1590/S0034-759020160108S8710056