The impact of conducting preclinical systematic reviews on researchers and their research: A mixed method case study.

Background: Systematic reviews (SRs) are cornerstones of evidence-based medicine and have contributed significantly to breakthroughs since the 1980's. However, preclinical SRs remain relatively rare despite their many advantages. Since 2011 the Dutch health funding organisation (ZonMw) has run a grant scheme dedicated to promoting the training, coaching and conduct of preclinical SRs.

Safety, Tolerability, and Feasibility of Young Plasma Infusion in the Plasma for Alzheimer Symptom Amelioration Study: A Randomized Clinical Trial.

Importance: Young mouse plasma restores memory in aged mice, but, to our knowledge, the effects are unknown in patients with Alzheimer disease (AD).

Objective: To assess the safety, tolerability, and feasibility of infusions of young fresh frozen plasma (yFFP) from donors age 18 to 30 years in patients with AD.

Design, Setting, And Participants: The Plasma for Alzheimer Symptom Amelioration (PLASMA) study randomized 9 patients under a double-blind crossover protocol to receive 4 once-weekly infusions of either 1 unit (approximately 250 mL) of yFFP from male donors or 250 mL of saline, followed by a 6-week washout and crossover to 4 once-weekly infusions of an alternate treatment.

Letter to the editor - round table unites to tackle culture change in an effort to improve animal research reporting.

A round table discussion was held during the LAVA-ESLAV-ECLAM conference on Reproducibility of Animal Studies on the 25th of September 2017 in Edinburgh. The aim of the round table was to discuss how to enhance the rate at which the quality of reporting animal research can be improved. This signed statement acknowledges the efforts that participant organizations have made towards improving the reporting of animal studies and confirms an ongoing commitment to drive further improvements, calling upon both academics and laboratory animal veterinarians to help make this cultural change.

A Bayesian spatial model for neuroimaging data based on biologically informed basis functions.

The dominant approach to neuroimaging data analysis employs the voxel as the unit of computation. While convenient, voxels lack biological meaning and their size is arbitrarily determined by the resolution of the image. Here, we propose a multivariate spatial model in which neuroimaging data are characterised as a linearly weighted combination of multiscale basis functions which map onto underlying brain nuclei or networks or nuclei.

Functional parcellation using time courses of instantaneous connectivity.

Functional neuroimaging studies have led to understanding the brain as a collection of spatially segregated functional networks. It is thought that each of these networks is in turn composed of a set of distinct sub-regions that together support each network's function. Considering the sub-regions to be an essential part of the brain's functional architecture, several strategies have been put forward that aim at identifying the functional sub-units of the brain by means of functional parcellations.

Functional anatomy of the human thalamus at rest.

In the present work, we used resting state-fMRI to investigate the functional anatomy of the thalamus at rest by applying an Independent Component Analysis to delineate thalamic substructures into stable and reproducible parcels for the left and right thalamus. We determined 15 functionally distinct thalamic parcels, which differed in laterality and size but exhibited a correspondence with 18 cytoarchitectonally defined nuclei. We characterized their structural connectivity in determining DWI based cortical fiber pathways and found selected projections to different cortical areas.

Attention-Deficit/Hyperactivity Disorder symptoms coincide with altered striatal connectivity.

Background: Cortico-striatal network dysfunction in attention-deficit/hyperactivity disorder (ADHD) is generally investigated by comparing functional connectivity of the main striatal sub-regions (i.e., putamen, caudate, and nucleus accumbens) between an ADHD and a control group.

Altered functional connectivity of the amygdaloid input nuclei in adolescents and young adults with autism spectrum disorder: a resting state fMRI study.

Background: Amygdala dysfunction is hypothesized to underlie the social deficits observed in autism spectrum disorders (ASD). However, the neurobiological basis of this hypothesis is underspecified because it is unknown whether ASD relates to abnormalities of the amygdaloid input or output nuclei. Here, we investigated the functional connectivity of the amygdaloid social-perceptual input nuclei and emotion-regulation output nuclei in ASD versus controls.

An investigation into the functional and structural connectivity of the Default Mode Network.

Connectivity analyses based on both resting-state (rs-)fMRI and diffusion weighted imaging studies suggest that the human brain contains regions that act as hubs for the entire brain, and that elements of the Default Mode Network (DMN) play a pivotal role in this network. In the present study, the detailed functional and structural connectivity of the DMN was investigated. Resting state fMRI (35 minute duration) and Diffusion Weighted Imaging (DWI) data (256 directions) were acquired from forty-seven healthy subjects at 3 T.

The Quest for EEG Power Band Correlation with ICA Derived fMRI Resting State Networks.

The neuronal underpinnings of blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) resting state networks (RSNs) are still unclear. To investigate the underlying mechanisms, specifically the relation to the electrophysiological signal, we used simultaneous recordings of electroencephalography (EEG) and fMRI during eyes open resting state (RS). Earlier studies using the EEG signal as independent variable show inconclusive results, possibly due to variability in the temporal correlations between RSNs and power in the low EEG frequency bands, as recently reported (Goncalves et al.

Electrophysiological correlation patterns of resting state networks in single subjects: a combined EEG-fMRI study.

With combined EEG-fMRI a powerful combination of methods was developed in the last decade that seems promising for answering fundamental neuroscientific questions by measuring functional processes of the human brain simultaneously with two complementary modalities. Recently, resting state networks (RSNs), representing brain regions of coherent BOLD fluctuations, raised major interest in the neuroscience community. Since RSNs are reliably found across subjects and reflect task related networks, changes in their characteristics might give insight to neuronal changes or damage, promising a broad range of scientific and clinical applications.

The effect of sport on computerized electrocardiogram measurements in college athletes.

Background: Broad criteria for abnormal electrocardiogram (ECG) findings, requiring additional testing, have been recommended for preparticipation exams (PPE) of athletes. As these criteria have not considered the sport in which athletes participate, we examined the effect of sports on the computerized ECG measurements obtained in college athletes.

Methods: During the Stanford 2007 PPE, computerized 12-lead ECGs (Schiller AG) were obtained in 641 athletes (350 male/291 female, age 19.

Neutrophil recruitment and barrier impairment in celiac disease: a genomic study.

Background & Aims: Celiac disease is an enteropathy featuring villous atrophy, crypt hyperplasia, and lymphocytosis. Tissue remodeling is driven by an inflammatory reaction to gluten in genetically susceptible individuals. The adaptive pathway is considered the major immune response but recent evidence has indicated the involvement of innate immunity as well.

Suspension-cultured BY-2 tobacco cells produce and mature immunologically active house dust mite allergens.

The replacement of crude allergen extracts by selected allergens currently represents a major goal for the improvement of allergy diagnosis and immunotherapy. Indeed, the development of molecularly defined vaccines would facilitate both standardization and enhance batch-to-batch reproducibility as well as treatment specificity. In this study, we have investigated the potential of tobacco plant cells to produce biologically active forms of the two major allergens from the house dust mite.

Myosin IXB variant increases the risk of celiac disease and points toward a primary intestinal barrier defect.

Celiac disease is probably the best-understood immune-related disorder. The disease presents in the small intestine and results from the interplay between multiple genes and gluten, the triggering environmental factor. Although HLA class II genes explain 40% of the heritable risk, non-HLA genes accounting for most of the familial clustering have not yet been identified.

"Coelionomics": towards understanding the molecular pathology of coeliac disease.

Coeliac disease (CD) is an inflammatory disorder of the small intestine characterised by a permanent intolerance to gluten-derived peptides. When gluten-derived peptides reach the lamina propria in CD patients, they provoke specific changes in the mucosa of their small intestine. Although the susceptibility to CD is strongly determined by environmental gluten, it is clearly a common genetic disorder.

The major grass pollen group 5 allergen from Dactylis glomerata and its C-terminal split product both behave as dimers: implications for allergen standardization.

Background: On SDS-PAGE grass pollen group-5 allergens migrate as a doublet with an apparent molecular mass (M(r)) of 25 kDa. Immunoblot analysis revealed additional group 5 reactivity at double and half this M(r). The aim of this study was to investigate these group 5 molecular entities and to compare their allergenicity and behavior in quantitative immunoassays.

Characterization of natural Dac g 1 variants: an alternative to recombinant group 1 allergens.

Background: Production of soluble correctly folded recombinant group 1 allergens has proven to be difficult. Purified natural group 1 allergens could be an alternative for application in immunotherapy.

Objective: Cloning and expression of recombinant Dac g 1; purification of natural Dac g 1 variants and immunochemical characterization of these molecules.

Substitution of Pichia pastoris-derived recombinant proteins with mannose containing O- and N-linked glycans decreases specificity of diagnostic tests.

Background: Recombinant proteins from Pichia pastoris need to be fully evaluated before used as diagnostic tools.

Objective: The objective of this study was to investigate whether glycosylation by P. pastoris interferes with the specificity of diagnostic tests.

Maturation of Pichia pastoris-derived recombinant pro-Der p 1 induced by deglycosylation and by the natural cysteine protease Der p 1 from house dust mite.

The mature cysteine protease from Dermatophgoides pteronyssinus, Der p 1, is a major house dust mite allergen. Its enzymatic activity has been shown to have pro-inflammatory effects that could also negatively influence efficacy of allergen-specific immunotherapy. The aim of this study was to express recombinant pro-Der p 1 (rpro-Der p 1) in the yeast Pichia pastoris and to study its maturation.

Immunochemical characterization of two Pichia pastoris-derived recombinant group 5 Dactylis glomerata isoallergens.

Background: Grass pollen of the Poaceae grasses are known to be highly allergenic. Major allergens from the species Lolium, Phleum, Poa and Holcus have been cloned and expressed as recombinant proteins, but of the important species Dactylis glomerata no recombinants are available.

Methods: Dac g 5 was cloned by PCR on the basis of homology with Lol p 5 and expressed in Pichia pastoris.

Beta2-glycoprotein I is proteolytically cleaved in vivo upon activation of fibrinolysis.

Beta2-glycoprotein I (beta2GPI) is a plasma glycoprotein with unknown physiological function(s). In in vitro experiments it has been demonstrated that beta2GPI has both anticoagulant properties, such as the inhibition of factor X and prothrombin activation and procoagulant properties, such as the inhibition of the anticoagulant activity of activated protein C. Besides this, beta2GPI bound to cardiolipin is recognized by antiphospholipid antibodies (aPL).