MEG spectral analysis in subtypes of mild cognitive impairment

Mild cognitive impairment (MCI) has been described as an intermediate stage between normal aging and dementia. Previous studies characterized the alterations of brain oscillatory activity at this stage, but little is known about the differences between single and multidomain amnestic MCI patients. In order to study the patterns of oscillatory magnetic activity in amnestic MCI subtypes, a total of 105 subjects underwent an eyes-closed resting-state magnetoencephalographic recording: 36 healthy controls, 33 amnestic single domain MCIs (a-sd-MCI), and 36 amnestic multidomain MCIs (a-md-MCI). Relative power values were calculated and compared among groups. Subsequently, relative power values were correlated with neuropsychological tests scores and hippocampal volumes. Both MCI groups showed an increase in relative power in lower frequency bands (delta and theta frequency ranges) and a decrease in power values in higher frequency bands (alpha and beta frequency ranges), as compared with the control group. More importantly, clear differences emerged from the comparison between the two amnestic MCI subtypes. The a-md-MCI group showed a significant power increase within delta and theta ranges and reduced relative power within alpha and beta ranges. Such pattern correlated with the neuropsychological performance, indicating that the a-md-MCI subtype is associated not only with a "slowing" of the spectrum but also with a poorer cognitive status. These results suggest that a-md-MCI patients are characterized by a brain activity profile that is closer to that observed in Alzheimer disease. Therefore, it might be hypothesized that the likelihood of conversion to dementia would be higher within this subtype

Seroprevalence and Risk Factors Associated to Mycobacterium bovis in Wild Artiodactyl Species from Southern Spain, 2006–2010

The control of bovine tuberculosis (bTB) is at a critical point in the last stage of eradication in livestock. Wildlife species recently have emerged infected with TB in Europe, particularly ungulates in the Iberian Peninsula. Epidemiological information regarding TB in wild ungulates including affected species, prevalence, associated risk factors and appropriate diagnostic methods need to be obtained in these countries

Spatial distribution and risk factors of Brucellosis in Iberian wild ungulates

<p>Abstract</p> <p>Background</p> <p>The role of wildlife as a brucellosis reservoir for humans and domestic livestock remains to be properly established. The aim of this work was to determine the aetiology, apparent prevalence, spatial distribution and risk factors for brucellosis transmission in several Iberian wild ungulates.</p> <p>Methods</p> <p>A multi-species indirect immunosorbent assay (iELISA) using <it>Brucella </it>S-LPS antigen was developed. In several regions having brucellosis in livestock, individual serum samples were taken between 1999 and 2009 from 2,579 wild bovids, 6,448 wild cervids and4,454 Eurasian wild boar (<it>Sus scrofa</it>), and tested to assess brucellosis apparent prevalence. Strains isolated from wild boar were characterized to identify the presence of markers shared with the strains isolated from domestic pigs.</p> <p>Results</p> <p>Mean apparent prevalence below 0.5% was identified in chamois (<it>Rupicapra pyrenaica</it>), Iberian wild goat (<it>Capra pyrenaica</it>), and red deer (<it>Cervus elaphus</it>). Roe deer (<it>Capreolus capreolus</it>), fallow deer (<it>Dama dama</it>), mouflon (<it>Ovis aries</it>) and Barbary sheep (<it>Ammotragus lervia</it>) tested were seronegative. Only one red deer and one Iberian wild goat resulted positive in culture, isolating <it>B. abortus </it>biovar 1 and <it>B. melitensis </it>biovar 1, respectively. Apparent prevalence in wild boar ranged from 25% to 46% in the different regions studied, with the highest figures detected in South-Central Spain. The probability of wild boar being positive in the iELISA was also affected by age, age-by-sex interaction, sampling month, and the density of outdoor domestic pigs. A total of 104 bacterial isolates were obtained from wild boar, being all identified as <it>B. suis </it>biovar 2. DNA polymorphisms were similar to those found in domestic pigs.</p> <p>Conclusions</p> <p>In conclusion, brucellosis in wild boar is widespread in the Iberian Peninsula, thus representing an important threat for domestic pigs. By contrast, wild ruminants were not identified as a significant brucellosis reservoir for livestock.</p

Impact of interstitial lung disease on the survival of systemic sclerosis with pulmonary arterial hypertension

To assess severity markers and outcomes of patients with systemic sclerosis (SSc) with or without pulmonary arterial hypertension (PAH-SSc/non-PAH-SSc), and the impact of interstitial lung disease (ILD) on PAH-SSc. Non-PAH-SSc patients from the Spanish SSc registry and PAH-SSc patients from the Spanish PAH registry were included. A total of 364 PAH-SSc and 1589 non-PAH-SSc patients were included. PAH-SSc patients had worse NYHA-functional class (NYHA-FC), worse forced vital capacity (FVC) (81.2 +/- 20.6% vs 93.6 +/- 20.6%, P < 0.001), worse tricuspid annular plane systolic excursion (TAPSE) (17.4 +/- 5.2 mm vs 19.9 +/- 6.7 mm, P < 0.001), higher incidence of pericardial effusion (30% vs 5.2%, P < 0.001) and similar prevalence of ILD (41.8% vs. 44.9%). In individuals with PAH-SSc, ILD was associated with worse hemodynamics and pulmonary function tests (PFT). Up-front combination therapy was used in 59.8% and 61.7% of patients with and without ILD, respectively. Five-year transplant-free survival rate was 41.1% in PAH-SSc patients and 93.9% in non-PAH-SSc patients (P < 0.001). Global survival of PAH-SSc patients was not affected by ILD regardless its severity. The multivariate survival analysis in PAH-SSc patients confirmed age at diagnosis, worse NYHA-FC, increased PVR, reduced DLCO, and lower management with up-front combination therapy as major risk factors. In conclusion, in PAH-SSc cohort risk of death was greatly increased by clinical, PFT, and hemodynamic factors, whereas it was decreased by up-front combination therapy. Concomitant ILD worsened hemodynamics and PFT in PAH-SSc but not survival regardless of FVC impairment

Impact of interstitial lung disease on the survival of systemic sclerosis with pulmonary arterial hypertension

To assess severity markers and outcomes of patients with systemic sclerosis (SSc) with or without pulmonary arterial hypertension (PAH-SSc/non-PAH-SSc), and the impact of interstitial lung disease (ILD) on PAH-SSc. Non-PAH-SSc patients from the Spanish SSc registry and PAH-SSc patients from the Spanish PAH registry were included. A total of 364 PAH-SSc and 1589 non-PAH-SSc patients were included. PAH-SSc patients had worse NYHA-functional class (NYHA-FC), worse forced vital capacity (FVC) (81.2 ± 20.6% vs 93.6 ± 20.6%, P &lt; 0.001), worse tricuspid annular plane systolic excursion (TAPSE) (17.4 ± 5.2 mm vs 19.9 ± 6.7 mm, P &lt; 0.001), higher incidence of pericardial effusion (30% vs 5.2%, P &lt; 0.001) and similar prevalence of ILD (41.8% vs. 44.9%). In individuals with PAH-SSc, ILD was associated with worse hemodynamics and pulmonary function tests (PFT). Up-front combination therapy was used in 59.8% and 61.7% of patients with and without ILD, respectively. Five-year transplant-free survival rate was 41.1% in PAH-SSc patients and 93.9% in non-PAH-SSc patients (P &lt; 0.001). Global survival of PAH-SSc patients was not affected by ILD regardless its severity. The multivariate survival analysis in PAH-SSc patients confirmed age at diagnosis, worse NYHA-FC, increased PVR, reduced DLCO, and lower management with up-front combination therapy as major risk factors. In conclusion, in PAH-SSc cohort risk of death was greatly increased by clinical, PFT, and hemodynamic factors, whereas it was decreased by up-front combination therapy. Concomitant ILD worsened hemodynamics and PFT in PAH-SSc but not survival regardless of FVC impairment

Interactions between four species in a complex wildlife: livestock disease community : implications for Mycobacterium bovis maintenance and transmission

Livestock diseases such as bovine tuberculosis can have considerable negative effects on human health and economic activity. Wildlife reservoirs often hinder disease eradication in sympatric livestock populations. Therefore, quantifying interactions between wildlife and livestock is an important aspect of understanding disease persistence. This study was conducted on an extensive cattle farm in southwest Spain, where cattle, domestic pigs, wild boar and red deer are considered to be part of a tuberculosis host community. We tested the hypothesis that the frequency of both types of interactions would be greater at food and water sites, due to the aggregation of individuals from multiple species at these locations. We measured direct and indirect interactions between individuals using GPS and proximity loggers. Over 57,000 direct interactions were recorded over a 2-year period, of which 875 (1.5 %) occurred between different species and 216 (0.38 %) occurred between wildlife and livestock. Most direct and indirect interactions occurred at water sites. Over 90 % of indirect interactions between wildlife and livestock took place within the estimated 3-day environmental survival time of Mycobacterium bovis in this habitat. Red deer home ranges and daily activity patterns revealed significant spatial and temporal overlaps with cattle, particularly in autumn. Suids and red deer also cross the farm boundary regularly, introducing a between-farm interaction risk. The infrequent occurrence of direct interactions between individuals from different species suggests that they are unlikely to be the sole mode of disease transmission and that indirect interactions may play an important role

One-Tube-Only Standardized Site-Directed Mutagenesis: An Alternative Approach to Generate Amino Acid Substitution Collections

Contains fulltext : 171086.PDF (publisher's version ) (Open Access)Site-directed mutagenesis (SDM) is a powerful tool to create defined collections of protein variants for experimental and clinical purposes, but effectiveness is compromised when a large number of mutations is required. We present here a one-tube-only standardized SDM approach that generates comprehensive collections of amino acid substitution variants, including scanning- and single site-multiple mutations. The approach combines unified mutagenic primer design with the mixing of multiple distinct primer pairs and/or plasmid templates to increase the yield of a single inverse-PCR mutagenesis reaction. Also, a user-friendly program for automatic design of standardized primers for Ala-scanning mutagenesis is made available. Experimental results were compared with a modeling approach together with stochastic simulation data. For single site-multiple mutagenesis purposes and for simultaneous mutagenesis in different plasmid backgrounds, combination of primer sets and/or plasmid templates in a single reaction tube yielded the distinct mutations in a stochastic fashion. For scanning mutagenesis, we found that a combination of overlapping primer sets in a single PCR reaction allowed the yield of different individual mutations, although this yield did not necessarily follow a stochastic trend. Double mutants were generated when the overlap of primer pairs was below 60%. Our results illustrate that one-tube-only SDM effectively reduces the number of reactions required in large-scale mutagenesis strategies, facilitating the generation of comprehensive collections of protein variants suitable for functional analysis

Technical management risks for transport infrastructures along whole life cycle: identification and intervention

RAGTIME is a Horizon 2020 project focused on development, demonstration and validation of an innovative infrastructures management approach. It lays out a whole system, based on standard multi-scale data models, able to facilitate a holistic management throughout the entire lifecycle of the infrastructure, providing an integrated view of risk based approach, implementing risk based models, resilient concepts and mitigation actions. It is structured in three modules: governance, finance and economic, and technical management. This paper is focused on RAGTIME’s technical management module. The main objective of this paper is to deal with technical risk assessment of the transport infrastructure approach based on an innovative 3D vector, defined by following variables: stakeholder (owner/citizenship, contractor and financier), life-cycle phase (evaluation-planning, procurement-decision, design-project, construction, and operation and maintenance) and infrastructure (rail, road, port and airport)This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 690660

Tailor-Made Protein Tyrosine Phosphatases: In Vitro Site-Directed Mutagenesis of PTEN and PTPRZ-B

In vitro site-directed mutagenesis (SDM) of protein tyrosine phosphatases (PTPs) is a commonly used approach to experimentally analyze PTP functions at the molecular and cellular level and to establish functional correlations with PTP alterations found in human disease. Here, using the tumor-suppressor PTEN and the receptor-type PTPRZ-B (short isoform from PTPRZ1 gene) phosphatases as examples, we provide a brief insight into the utility of specific mutations in the experimental analysis of PTP functions. We describe a standardized, rapid, and simple method of mutagenesis to perform single and multiple amino acid substitutions, as well as deletions of short nucleotide sequences, based on one-step inverse PCR and DpnI restriction enzyme treatment. This method of SDM is generally applicable to any other protein of interest