Factors Associated with Response to Acetylcholinesterase Inhibition in Dementia:A Cohort Study from a Secondary Mental Health Care Case Register in London

Background: Acetylcholinesterase inhibitors (AChEIs) are widely used to delay cognitive decline in Alzheimer's disease. Observational studies in routine clinical practice have shown cognitive improvement in some groups of patients receiving these agents but longitudinal trajectories before and after AChEI initiation have not previously been considered.  Objectives: To compare trajectories of cognitive function before and after AChEI initiation and investigate predictors of these differences.  Method: A retrospective longitudinal study was constructed using data from 2460 patients who received AChEIs and who had routine data on cognitive function (Mini-Mental State Examination; MMSE) before and after AChEI initiation. Longitudinal MMSE change was modelled using three-piece linear mixed models with the following segments: 0-12 months prior to AChEI initiation, 0-6 months and 6-36 months after initiation.  Results: MMSE decline was reversed (in that the slope was improved by an average 4.2 units per year, 95% CI 3.5-4.8) during the 6-month period following AChEI initiation compared with the slope in the one year period before AChEI initiation. The slope in the period from 6-36 months following AChEI initiation returned to the pre-initiation downward trajectory. The differences in slopes in the 1 year period prior to AChEI initiation and in the 6 months after initiation were smaller among those with higher MMSE scores at the time of AChEI initiation, among those who received a vascular dementia diagnosis at any point, and among those receiving antipsychotic agents.  Conclusion: In this naturalistic observational study, changes in cognitive trajectories around AChEI initiation were similar to those reported in randomised controlled trials. The magnitude of the difference in slopes between the 1 year period prior to AChEI initiation and the 6 month period after AChEI initiation was related to level of cognitive function at treatment initiation, vascular comorbidity and antipsychotic use

The effectiveness of problem solving therapy for stroke patients: Study protocol for a pragmatic randomized controlled trial

Background: Coping style is one of the determinants of health-related quality of life after stroke. Stroke patients make less use of active problem-oriented coping styles than other brain damaged patients. Coping styles can be influenced by means of intervention. The primary aim of this study is to investigate if Problem Solving Therapy is an effective group intervention for improving coping style and health-related quality of life in stroke patients. The secondary aim is to determine the effect of Problem Solving Therapy on depression, social participation, health care consumption, and to determine the cost-effectiveness of the intervention.Methods/design: We strive to include 200 stroke patients in the outpatient phase of rehabilitation treatment, using a multicenter pragmatic randomized controlled trial with one year follow-up. Patients in the intervention group will receive Problem Solving Therapy in addition to the standard rehabilitation program. The intervention will be provided in an open group design, with a continuous flow of patients. Primary outcome measures are coping style and health-related quality of life. Secondary outcome measures are depression, social participation, health care consumption, and the cost-effectiveness of the intervention.Discussion: We designed our study as close to the implementation in practice as possible, using a pragmatic randomized trial and open group design, to represent a realistic estimate of the effectiveness of the intervention. If effective, Problem Solving Therapy is an inexpensive, deliverable and sustainable group intervention for stroke rehabilitation programs.Trial registration: Nederlands Trial Register, NTR2509

Comparison of Two Multilocus Sequence Based Genotyping Schemes for Leptospira Species

Two independent multilocus sequence based genotyping schemes (denoted here as 7L and 6L for schemes with 7 and 6 loci, respectively) are in use for Leptospira spp., which has led to uncertainty as to which should be adopted by the scientific community. The purpose of this study was to apply the two schemes to a single collection of pathogenic Leptospira, evaluate their performance, and describe the practical advantages and disadvantages of each scheme. We used a variety of phylogenetic approaches to compare the output data and found that the two schemes gave very similar results. 7L has the advantage that it is a conventional multi-locus sequencing typing (MLST) scheme based on housekeeping genes and is supported by a publically accessible database by which genotypes can be readily assigned as known or new sequence types by any investigator, but is currently only applicable to L. interrogans and L. kirschneri. Conversely, 6L can be applied to all pathogenic Leptospira spp., but is not a conventional MLST scheme by design and is not available online. 6L sequences from 271 strains have been released into the public domain, and phylogenetic analysis of new sequences using this scheme requires their download and offline analysis

Gender differences in hemispheric asymmetry for face processing

BACKGROUND: Current cognitive neuroscience models predict a right-hemispheric dominance for face processing in humans. However, neuroimaging and electromagnetic data in the literature provide conflicting evidence of a right-sided brain asymmetry for decoding the structural properties of faces. The purpose of this study was to investigate whether this inconsistency might be due to gender differences in hemispheric asymmetry. RESULTS: In this study, event-related brain potentials (ERPs) were recorded in 40 healthy, strictly right-handed individuals (20 women and 20 men) while they observed infants' faces expressing a variety of emotions. Early face-sensitive P1 and N1 responses to neutral vs. affective expressions were measured over the occipital/temporal cortices, and the responses were analyzed according to viewer gender. Along with a strong right hemispheric dominance for men, the results showed a lack of asymmetry for face processing in the amplitude of the occipito-temporal N1 response in women to both neutral and affective faces. CONCLUSION: Men showed an asymmetric functioning of visual cortex while decoding faces and expressions, whereas women showed a more bilateral functioning. These results indicate the importance of gender effects in the lateralization of the occipito-temporal response during the processing of face identity, structure, familiarity, or affective content

Restricted Expression of Epstein-Barr Virus Latent Genes in Murine B Cells Derived from Embryonic Stem Cells

Background: Several human malignancies are associated with Epstein-Barr virus (EBV) and more than 95 % of the adult human population carries this virus lifelong. EBV efficiently infects human B cells and persists in this cellular compartment latently. EBV-infected B cells become activated and growth transformed, express a characteristic set of viral latent genes, and acquire the status of proliferating lymphoblastoid cell lines in vitro. Because EBV infects only primate cells, it has not been possible to establish a model of infection in immunocompetent rodents. Such a model would be most desirable in order to study EBV’s pathogenesis and latency in a suitable and amenable host. Methodology/Principal Findings: We stably introduced recombinant EBV genomes into mouse embryonic stem cells and induced their differentiation to B cells in vitro to develop the desired model. In vitro differentiated murine B cells maintained the EBV genomes but expression of viral genes was restricted to the latent membrane proteins (LMPs). In contrast to human B cells, EBV’s nuclear antigens (EBNAs) were not expressed detectably and growth transformed murine B cells did not arise in vitro. Aberrant splicing and premature termination of EBNA mRNAs most likely prevented the expression of EBNA genes required for B-cell transformation. Conclusions/Significance: Our findings indicate that fundamental differences in gene regulation between mouse and ma

Metal-responsive gene regulation and metal transport in Helicobacter species

Helicobacter species are among the most successful colonizers of the mammalian gastrointestinal and hepatobiliary tract. Colonization is usually lifelong, indicating that Helicobacter species have evolved intricate mechanisms of dealing with stresses encountered during colonization of host tissues, like restriction of essential metal ions. The recent availability of genome sequences of the human gastric pathogen Helicobacter pylori, the murine enterohepatic pathogen Helicobacter hepaticus and the unannotated genome sequence of the ferret gastric pathogen Helicobacter mustelae has allowed for comparitive genome analyses. In this review we present such analyses for metal transporters, metal-storage and metal-responsive regulators in these three Helicobacter species, and discuss possible contributions of the differences in metal metabolism in adaptation to the gastric or enterohepatic niches occupied by Helicobacter species

In vitro mycorrhization of micropropagated plants: studies on Castanea sativa Mill.

In vitro mycorrhization can be made by several axenic and nonaxenic techniques but criticism exists about their artificiality and inability to reproduce under natural conditions. However, artificial mycorrhization under controlled conditions can provide important information about the physiology of symbiosis. Micropropagated Castanea sativa plants were inoculated with the mycorrhizal fungus Pisolithus tinctorius after in vitro rooting. The mycorrhizal process was monitored at regular intervals in order to evaluate the mantle and hartig net formation, and the growth rates of mycorrhizal and nonmycorrhizal plants. Plant roots show fungal hyphae adhesion at the surface after 24 hours of mycorrhizal induction. After 20 days a mantle can be observed and a hartig net is forming although the morphology of the epidermal cells remains unaltered. At 30 days of root–fungus contact the hartig net is well developed and the epidermal cells are already enlarged. After 50 days of mycorrhizal induction, growth was higher for mycorrhizal plants than for nonmycorrhizal ones. The length of the major roots was lower in mycorrhizal plants after 40 days. Fresh and dry weights were higher in mycorrhizal plants after 30 days. The growth rates of chestnut mycorrhizal plants are in agreement with the morphological development of the mycorrhizal structures observed at each mycorrhizal time. The assessment of symbiotic establishment takes into account the formation of a mantle and a hartig net that were already developed at 30 days, when differences between fresh and dry weights of mycorrhizal and nonmycorrhizal plants can be quantified. In vitro conditions, mycorrhization influences plant physiology after 20 days of root–fungus contact, namely in terms of growth rates. Fresh and dry weights, heights, stem diameter and growth rates increased while major root growth rate decreased in mycorrhizal plants.Springe

Flow shop rescheduling under different types of disruption

This is an Accepted Manuscript of an article published by Taylor & Francis in International Journal of Production Research on 2013, available online:http://www.tandfonline.com/10.1080/00207543.2012.666856Almost all manufacturing facilities need to use production planning and scheduling systems to increase productivity and to reduce production costs. Real-life production operations are subject to a large number of unexpected disruptions that may invalidate the original schedules. In these cases, rescheduling is essential to minimise the impact on the performance of the system. In this work we consider flow shop layouts that have seldom been studied in the rescheduling literature. We generate and employ three types of disruption that interrupt the original schedules simultaneously. We develop rescheduling algorithms to finally accomplish the twofold objective of establishing a standard framework on the one hand, and proposing rescheduling methods that seek a good trade-off between schedule quality and stability on the other.The authors would like to thank the anonymous referees for their careful and detailed comments that helped to improve the paper considerably. This work is partially financed by the Small and Medium Industry of the Generalitat Valenciana (IMPIVA) and by the European Union through the European Regional Development Fund (FEDER) inside the R + D program "Ayudas dirigidas a Institutos tecnologicos de la Red IMPIVA" during the year 2011, with project number IMDEEA/2011/142.Katragjini Prifti, K.; Vallada Regalado, E.; Ruiz García, R. (2013). Flow shop rescheduling under different types of disruption. International Journal of Production Research. 51(3):780-797. https://doi.org/10.1080/00207543.2012.666856S780797513Abumaizar, R. J., & Svestka, J. A. 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Soluble Immune Complexes Shift the TLR-Induced Cytokine Production of Distinct Polarized Human Macrophage Subsets towards IL-10

Contains fulltext : 109563.pdf (publisher's version ) (Open Access)BACKGROUND: Costimulation of murine macrophages with immune complexes (ICs) and TLR ligands leads to alternative activation. Studies on human myeloid cells, however, indicate that ICs induce an increased pro-inflammatory cytokine production. This study aimed to clarify the effect of ICs on the pro- versus anti-inflammatory profile of human polarized macrophages. MATERIALS AND METHODS: Monocytes isolated from peripheral blood of healthy donors were polarized for four days with IFN-gamma, IL-4, IL-10, GM-CSF, M-CSF, or LPS, in the presence or absence of heat aggregated gamma-globulins (HAGGs). Phenotypic polarization markers were measured by flow cytometry. Polarized macrophages were stimulated with HAGGs or immobilized IgG alone or in combination with TLR ligands. TNF, IL-6, IL-10, IL-12, and IL-23 were measured by Luminex and/or RT-qPCR. RESULTS: HAGGs did not modulate the phenotypic polarization and the cytokine production of macrophages. However, HAGGs significantly altered the TLR-induced cytokine production of all polarized macrophage subsets, with the exception of MPhi(IL-4). In particular, HAGGs consistently enhanced the TLR-induced IL-10 production in both classically and alternatively polarized macrophages (M1 and M2). The effect of HAGGs on TNF and IL-6 production was less pronounced and depended on the polarization status, while IL-23p19 and IL-12p35 expression was not affected. In contrast with HAGGs, immobilized IgG induced a strong upregulation of not only IL-10, but also TNF and IL-6. CONCLUSION: HAGGs alone do not alter the phenotype and cytokine production of in vitro polarized human macrophages. In combination with TLR-ligands, however, HAGGs but not immobilized IgG shift the cytokine production of distinct macrophage subsets toward IL-10

Enhanced Fatty Acid Oxidation and FATP4 Protein Expression after Endurance Exercise Training in Human Skeletal Muscle

FATP1 and FATP4 appear to be important for the cellular uptake and handling of long chain fatty acids (LCFA). These findings were obtained from loss- or gain of function models. However, reports on FATP1 and FATP4 in human skeletal muscle are limited. Aerobic training enhances lipid oxidation; however, it is not known whether this involves up-regulation of FATP1 and FATP4 protein. Therefore, the aim of this project was to investigate FATP1 and FATP4 protein expression in the vastus lateralis muscle from healthy human individuals and to what extent FATP1 and FATP4 protein expression were affected by an increased fuel demand induced by exercise training. Eight young healthy males were recruited to the study. All subjects were non smokers and did not participate in regular physical activity (<1 time per week for the past 6 months, VO2peak 3.4±0.1 l O2 min−1). Subjects underwent an 8 week supervised aerobic training program. Training induced an increase in VO2peak from 3.4±0.1 to 3.9±0.1 l min−1 and citrate synthase activity was increased from 53.7±2.5 to 80.8±3.7 µmol g−1 min−1. The protein content of FATP4 was increased by 33%, whereas FATP1 protein content was reduced by 20%. Interestingly, at the end of the training intervention a significant association (r2 = 0.74) between the observed increase in skeletal muscle FATP4 protein expression and lipid oxidation during a 120 min endurance exercise test was observed. In conclusion, based on the present findings it is suggested that FATP1 and FATP4 proteins perform different functional roles in handling LCFA in skeletal muscle with FATP4 apparently more important as a lipid transport protein directing lipids for lipid oxidation