278 research outputs found
Diagnostic tests for Niemann-Pick disease type C (NP-C): A critical review
Niemann-Pick disease type C (NP-C) is a neurovisceral lysosomal cholesterol trafficking and lipid storage disorder caused by mutations in one of the two genes, NPC1 or NPC2. Diagnosis has often been a difficult task, due to the wide range in age of onset of NP-C and clinical presentation of the disease, combined with the complexity of the cell biology (filipin) laboratory testing, even in combination with genetic testing. This has led to substantial delays in diagnosis, largely depending on the access to specialist centres and the level of knowledge about NP-C of the physician in the area. In recent years, advances in mass spectrometry has allowed identification of several sensitive plasma biomarkers elevated in NP-C (e.g. cholestane-3β,5α,6β-triol, lysosphingomyelin isoforms and bile acid metabolites), which, together with the concomitant progress in molecular genetic technology, have greatly impacted the strategy of laboratory testing. Specificity of the biomarkers is currently under investigation and other pathologies are being found to also result in elevations. Molecular genetic testing also has its limitations, notably with unidentified mutations and the classification of new variants. This review is intended to increase awareness on the currently available approaches to laboratory diagnosis of NP-C, to provide an up to date, comprehensive and critical evaluation of the various techniques (cell biology, biochemical biomarkers and molecular genetics), and to briefly discuss ongoing/future developments. The use of current tests in proper combination enables a rapid and correct diagnosis in a large majority of cases. However, even with recent progress, definitive diagnosis remains challenging in some patients, for whom combined genetic/biochemical/cytochemical markers do not provide a clear answer. Expertise and reference laboratories thus remain essential, and further work is still required to fulfill unmet needs
Smaller medial temporal lobe volumes in individuals with subjective cognitive decline and biomarker evidence of Alzheimer's disease—Data from three memory clinic studies
INTRODUCTION: Previous studies showed associations of brain volume differences and biomarker evidence for Alzheimer's disease (AD) in subjective cognitive decline (SCD). The consistency of this finding across SCD studies has not been investigated. METHODS: We studied gray matter volume differences between SCD subjects with and without cerebrospinal fluid biomarker evidence for AD across three European memory clinic samples (DZNE Longitudinal Cognitive Impairment and Dementia study, Amsterdam, Barcelona). Analysis of covariance models with samples and cerebrospinal fluid biomarkers as between-subject factors were calculated. RESULTS: A significant main effect for AD biomarker (Aβ42- > Aβ42+) in the left medial temporal lobe (MTL) was found, with the absence of main effects for sample or interaction effects between AD biomarker and sample. This indicates consistent lower left MTL volume across three samples in SCD subjects with abnormal Aβ42 levels. DISCUSSION: Our results support the model that in the presence of AD pathology, SCD corresponds to the late preclinical stage (stage 2 of AD) with smaller MTL volumes
Development of superlattice CrNNbN coatings for joint replacements deposited by High Power Impulse Magnetron Sputtering
The demand for reliable coating on medical implants is ever growing. In this research, enhanced performance of medical implants was achieved by a CrN/NbN coating utilising nanoscale multilayer/superlattice structure. The advantages of the novel High Power Impulse Magnetron Sputtering technology, namely its unique highly ionised plasma were exploited to deposit dense and strongly adherent coatings on Co-Cr implants. TEM analyses revealed coating superlattice structure with bi-layer thickness of 3.5 nm. CrN/NbN deposited on Co-Cr samples showed exceptionally high adhesion, critical load values of LC2= 50 N in scratch adhesion tests. Nanoindentation tests showed high hardness of 34 GPa and Young's modulus of 447 GPa. Low coefficient of friction (µ) 0.49 and coating wear coefficient (KC) = 4.94 x 10-16 m3N-1m-1 were recorded in dry sliding tests. Metal ion release studies showed a reduction in Co, Cr and Mo release at physiological and elevated temperatures, (70 oC) to almost undetectable levels (<1 ppb). Rotating beam fatigue testing showed a significant increase in fatigue strength from 349±59 MPa (uncoated) to 539±59 MPa (coated). In vitro biological testing has been performed in order to assess the safety of the coating in biological environment, cytotoxicity, genotoxicity and sensitisation testing have been performed, all showing no adverse effects.
Keywords: Orthopaedic implant, High Power Impulse Magnetron Sputtering, Superlattice coating, Corrosion, Biocompatibility
On the influence of the cosmological constant on gravitational lensing in small systems
The cosmological constant Lambda affects gravitational lensing phenomena. The
contribution of Lambda to the observable angular positions of multiple images
and to their amplification and time delay is here computed through a study in
the weak deflection limit of the equations of motion in the Schwarzschild-de
Sitter metric. Due to Lambda the unresolved images are slightly demagnified,
the radius of the Einstein ring decreases and the time delay increases. The
effect is however negligible for near lenses. In the case of null cosmological
constant, we provide some updated results on lensing by a Schwarzschild black
hole.Comment: 8 pages, 1 figure; v2: extended discussion on the lens equation,
references added, results unchanged, in press on PR
Palaeoclimatic conditions in the Mediterranean explain genetic diversity of Posidonia oceanica seagrass meadows
Past environmental conditions in the Mediterranean Sea have been proposed as main drivers of the current patterns of distribution of genetic structure of the seagrass Posidonia oceanica, the foundation species of one of the most important ecosystems in the Mediterranean Sea. Yet, the location of cold climate refugia (persistence regions) for this species during the Last Glacial Maximum (LGM) is not clear, precluding the understanding of its biogeographical history. We used Ecological Niche Modelling together with existing phylogeographic data to locate Pleistocene refugia in the Mediterranean Sea and to develop a hypothetical past biogeographical distribution able to explain the genetic diversity presently found in P. oceanica meadows. To do that, we used an ensemble approach of six predictive algorithms and two Ocean General Circulation Models. The minimum SST in winter and the maximum SST in summer allowed us to hindcast the species range during the LGM. We found separate glacial refugia in each Mediterranean basin and in the Central region. Altogether, the results suggest that the Central region of the Mediterranean Sea was the most relevant cold climate refugium, supporting the hypothesis that long-term persistence there allowed the region to develop and retain its presently high proportion of the global genetic diversity of P. oceanica.Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) [SFRH/BPD/85040/2012]; FCT [UID/Multi/04326/2013, FCT-BIODIVERSA/004/2015]; Pew foundation (USA)info:eu-repo/semantics/publishedVersio
Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer's disease in rodent models.
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase-1 (COX-1) and COX-2 enzymes. The NLRP3 inflammasome is a multi-protein complex responsible for the processing of the proinflammatory cytokine interleukin-1β and is implicated in many inflammatory diseases. Here we show that several clinically approved and widely used NSAIDs of the fenamate class are effective and selective inhibitors of the NLRP3 inflammasome via inhibition of the volume-regulated anion channel in macrophages, independently of COX enzymes. Flufenamic acid and mefenamic acid are efficacious in NLRP3-dependent rodent models of inflammation in air pouch and peritoneum. We also show therapeutic effects of fenamates using a model of amyloid beta induced memory loss and a transgenic mouse model of Alzheimer's disease. These data suggest that fenamate NSAIDs could be repurposed as NLRP3 inflammasome inhibitors and Alzheimer's disease therapeutics
TRY plant trait database - enhanced coverage and open access
Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives
Adult pneumococcal meningitis presenting with normocellular cerebrospinal fluid: two case reports
Prevalence of abnormal Alzheimer’s disease biomarkers in patients with subjective cognitive decline: cross-sectional comparison of three European memory clinic samples
INTRODUCTION: Subjective cognitive decline (SCD) in cognitively unimpaired older individuals has been recognized as an early clinical at-risk state for Alzheimer’s disease (AD) dementia and as a target population for future dementia prevention trials. Currently, however, SCD is heterogeneously defined across studies, potentially leading to variations in the prevalence of AD pathology. Here, we compared the prevalence and identified common determinants of abnormal AD biomarkers in SCD across three European memory clinics participating in the European initiative on harmonization of SCD in preclinical AD (Euro-SCD). METHODS: We included three memory clinic SCD samples with available cerebrospinal fluid (CSF) biomaterial (IDIBAPS, Barcelona, Spain, n = 44; Amsterdam Dementia Cohort (ADC), The Netherlands, n = 50; DELCODE multicenter study, Germany, n = 42). CSF biomarkers (amyloid beta (Aβ)42, tau, and phosphorylated tau (ptau181)) were centrally analyzed in Amsterdam using prespecified cutoffs to define prevalence of pathological biomarker concentrations. We used logistic regression analysis in the combined sample across the three centers to investigate center effects with regard to likelihood of biomarker abnormality while taking potential common predictors (e.g., age, sex, apolipoprotein E (APOE) status, subtle cognitive deficits, depressive symptoms) into account. RESULTS: The prevalence of abnormal Aβ42, but not tau or ptau181, levels was different across centers (64% DELCODE, 57% IDIBAPS, 22% ADC; p < 0.001). Logistic regression analysis revealed that the likelihood of abnormal Aβ42 (and also abnormal tau or ptau181) levels was predicted by age and APOE status. For Aβ42 abnormality, we additionally observed a center effect, indicating between-center heterogeneity not explained by age, APOE, or the other included covariates. CONCLUSIONS: While heterogeneous frequency of abnormal Aβ42 was partly explained by between-sample differences in age range and APOE status, the additional observation of center effects indicates between-center heterogeneity that may be attributed to different recruitment procedures. These findings highlight the need for the development of harmonized recruitment protocols for SCD case definition in multinational studies to achieve similar enrichment rates of preclinical AD
Transmission of methicillin-resistant Staphylococcus aureus in long-term care facilities and their related healthcare networks
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