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Transgenic APP23 mice were generated to model Alzheimer's disease. The APP23 model develops pathological features, learning deficits, and memory deficits analogous to dementing patients. In this report, transgenic mice exhibited several behavioral disturbances indicating the presence of neuropsychiatric symptoms of dementia. Aiming to verify whether the model also develops other behavioral problems, the authors investigated ingestive behavior in APP23 males of 3, 6 and 12 months. In addition, body weights of a naive male group were longitudinally monitored starting at weaning. Olfactory acuity was evaluated in mice of different age groups. Although olfactory functioning of APP23 mice appeared intact, they drank more and took more food pellets compared with wild-type littermates during a 1-week registration period. From the age of 4.5 weeks onward, APP23 males weighed significantly less than their control littermates, whereas this difference became more prominent with increasing age. Our results suggest the presence of a hypermetabolic state in this model. This is the first report, evidencing the presence of changes in eating and drinking behavior in a single transgenic Alzheimer mouse model.status: publishe

Bayesian sequential integration within a preclinical pharmacokinetic and pharmacodynamic modeling framework:Lessons learned

The present manuscript aims to discuss the implications of sequential knowledge integration of small preclinical trials in a Bayesian pharmacokinetic and pharmacodynamic (PK-PD) framework. While, at first sight, a Bayesian PK-PD framework seems to be a natural framework to allow for sequential knowledge integration, the scope of this paper is to highlight some often-overlooked challenges while at the same time providing some guidances in the many and overwhelming choices that need to be made. Challenges as well as opportunities will be discussed that are related to the impact of (1) the prior specification, (2) the choice of random effects, (3) the type of sequential integration method. In addition, it will be shown how the success of a sequential integration strategy is highly dependent on a carefully chosen experimental design when small trials are analyzed

Differential effects of proteins and carbohydrates on postprandial blood pressure-related responses

Diet composition may affect blood pressure (BP), but the mechanisms are unclear. The aim of the present study was to compare postprandial BP-related responses to the ingestion of pea protein, milk protein and egg-white protein. In addition, postprandial BP-related responses to the ingestion of maltodextrin were compared with those to the ingestion of sucrose and a protein mix. We hypothesised that lower postprandial total peripheral resistance (TPR) and BP levels would be accompanied by higher plasma concentrations of nitric oxide, insulin, glucagon-like peptide 1 (GLP-1) and glucagon. On separate occasions, six meals were tested in a randomised order in forty-eight overweight or obese adults with untreated elevated BP. Postprandial responses of TPR, BP and plasma concentrations of insulin, glucagon, GLP-1 and nitrite, nitroso compounds (RXNO) and S-nitrosothiols (NO(x)) were measured for 4 h. No differences were observed in TPR responses. Postprandial BP levels were higher after the ingestion of the egg-white-protein meal than after that of meals containing the other two proteins (P≤ 0·01). The ingestion of the pea-protein meal induced the highest NO(x) response (P≤ 0·006). Insulin and glucagon concentrations were lowest after the ingestion of the egg-white-protein meal (P≤ 0·009). Postprandial BP levels were lower after the ingestion of the maltodextrin meal than after that of the protein mix and sucrose meals (P≤ 0·004), while postprandial insulin concentrations were higher after the ingestion of the maltodextrin meal than after that of the sucrose and protein mix meals after 1-2 h (P≤ 0·0001). Postprandial NO(x), GLP-1 and glucagon concentrations were lower after the ingestion of the maltodextrin meal than after that of the protein mix meal (P≤ 0·008). In conclusion, different protein and carbohydrate sources induce different postprandial BP-related responses, which may be important for BP management. Lower postprandial BP levels are not necessarily accompanied by higher NO(x), insulin, glucagon or GLP-1 responses

Non-human primate to human immunobridging to infer the protective effect of an Ebola virus vaccine candidate

Action Contro

Visualization and Curve-Parameter Estimation Strategies for Efficient Exploration of Phenotype Microarray Kinetics

The Phenotype MicroArray (OmniLog® PM) system is able to simultaneously capture a large number of phenotypes by recording an organism's respiration over time on distinct substrates. This technique targets the object of natural selection itself, the phenotype, whereas previously addressed '-omics' techniques merely study components that finally contribute to it. The recording of respiration over time, however, adds a longitudinal dimension to the data. To optimally exploit this information, it must be extracted from the shapes of the recorded curves and displayed in analogy to conventional growth curves.The free software environment R was explored for both visualizing and fitting of PM respiration curves. Approaches using either a model fit (and commonly applied growth models) or a smoothing spline were evaluated. Their reliability in inferring curve parameters and confidence intervals was compared to the native OmniLog® PM analysis software. We consider the post-processing of the estimated parameters, the optimal classification of curve shapes and the detection of significant differences between them, as well as practically relevant questions such as detecting the impact of cultivation times and the minimum required number of experimental repeats.We provide a comprehensive framework for data visualization and parameter estimation according to user choices. A flexible graphical representation strategy for displaying the results is proposed, including 95% confidence intervals for the estimated parameters. The spline approach is less prone to irregular curve shapes than fitting any of the considered models or using the native PM software for calculating both point estimates and confidence intervals. These can serve as a starting point for the automated post-processing of PM data, providing much more information than the strict dichotomization into positive and negative reactions. Our results form the basis for a freely available R package for the analysis of PM data

Characterizing persistent disturbing behavior using longitudinal and multivariate techniques

Persistent disturbing behavior (PDB) refers to a chronic condition in therapy-resistant psychiatric patients. Since these patients are highly unstable and difficult to maintain in their natural living environment and even in hospital wards, it is important to properly characterize this group. Previous studies in the Belgian province of Limburg indicated that the size of this group was larger than anticipated. Here, using a score calculated from longitudinal psychiatric registration data in 611 patients, we characterize the difference between PDB patients and a set of control patients. These differences are studied both at a given point in time, using discriminant analysis, as well as in terms of the evolution of the score over time, using longitudinal data analysis methods. Further, using clustering techniques, the group of PDB patients is split into two subgroups, characterized in terms of a number of ordinal scores. Such findings are useful from a scientific as well as from an organizational point of view. © 2010 Taylor & Francis.status: publishe

Digital nerve injuries: a review of predictors of sensory recovery after microsurgical digital nerve repair

BACKGROUND: Optimal surgical management of digital nerve lesions remains uncertain despite the publication of numerous studies. The purposes of this review were primarily to analyze whether there is a superior surgical technique for digital nerve repair and secondarily to statistically verify the variables to be predictors of sensory recovery. METHODS: A literature search was performed using PubMed including citation from MEDLINE. Studies were included if they involved patients with digital nerve lacerations in whom end-to-end neurorrhaphy, nerve grafts, conduits, or end-to-side neurorrhaphy were performed. Further, the sensory outcome had to be assessed according to the modified American Society for Surgery of the Hand guidelines to stratify for two-point discrimination in millimeters. The variables age, follow-up, delay in repair, type of trauma, and gap length were extracted. The association between each predictor and response was assessed using a linear mixed model and corrected for heterogeneity between studies. Significance was considered present at p ≤ 0.05. RESULTS: Of the 34 articles found, 14 articles were included giving appropriate individual data for 191 nerves. There was no statistically significant difference in outcome between operation techniques. Age and follow-up were verified predictors of sensory recovery. CONCLUSION: In this review, the type of operation for digital nerve repair does not influence sensory outcome. However, we verified outcome to be influenced by the patient’s age and the follow-up period. To add more scientific evidence to our results, larger cohort prospective studies need to be done with better detailed description of data