Cerebrospinal fluid biomarkers in human genetic transmissible spongiform encephalopathies

The 14-3-3 protein test has been shown to support the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) when associated with an adequate clinical context, and a high differential potential for the diagnosis of sporadic CJD has been attributed to other cerebrospinal fluid (CSF) proteins such as tau protein, S100b and neuron specific enolase (NSE). So far there has been only limited information available about biochemical markers in genetic transmissible spongiform encephalopathies (gTSE), although they represent 10–15% of human TSEs. In this study, we analyzed CSF of 174 patients with gTSEs for 14-3-3 (n = 166), tau protein (n = 78), S100b (n = 46) and NSE (n = 50). Levels of brain-derived proteins in CSF varied in different forms of gTSE. Biomarkers were found positive in the majority of gCJD (81%) and insert gTSE (69%), while they were negative in most cases of fatal familial insomnia (13%) and Gerstmann-Sträussler-Scheinker syndrome (10%). Disease duration and codon 129 genotype influence the findings in a different way than in sporadic CJD

Brain-derived proteins in the CSF, do they correlate with brain pathology in CJD?

BACKGROUND: Brain derived proteins such as 14-3-3, neuron-specific enolase (NSE), S 100b, tau, phosphorylated tau and Aβ(1–42 )were found to be altered in the cerebrospinal fluid (CSF) in Creutzfeldt-Jakob disease (CJD) patients. The pathogenic mechanisms leading to these abnormalities are not known, but a relation to rapid neuronal damage is assumed. No systematic analysis on brain-derived proteins in the CSF and neuropathological lesion profiles has been performed. METHODS: CSF protein levels of brain-derived proteins and the degree of spongiform changes, neuronal loss and gliosis in various brain areas were analyzed in 57 CJD patients. RESULTS: We observed three different patterns of CSF alteration associated with the degree of cortical and subcortical changes. NSE levels increased with lesion severity of subcortical areas. Tau and 14-3-3 levels increased with minor pathological changes, a negative correlation was observed with severity of cortical lesions. Levels of the physiological form of the prion protein (PrP(c)) and Aβ(1–42 )levels correlated negatively with cortical pathology, most clearly with temporal and occipital lesions. CONCLUSION: Our results indicate that the alteration of levels of brain-derived proteins in the CSF does not only reflect the degree of neuronal damage, but it is also modified by the localization on the brain pathology. Brain specific lesion patterns have to be considered when analyzing CSF neuronal proteins

Meteorites on Mars observed with the Mars Exploration Rovers

Reduced weathering rates due to the lack of liquid water and significantly greater typical surface ages should result in a higher density of meteorites on the surface of Mars compared to Earth. Several meteorites were identified among the rocks investigated during Opportunity’s traverse across the sandy Meridiani plains. Heat Shield Rock is a IAB iron meteorite and has been officially recognized as ‘‘Meridiani Planum.’’ Barberton is olivine-rich and contains metallic Fe in the form of kamacite, suggesting a meteoritic origin. It is chemically most consistent with a mesosiderite silicate clast. Santa Catarina is a brecciated rock with a chemical and mineralogical composition similar to Barberton. Barberton, Santa Catarina, and cobbles adjacent to Santa Catarina may be part of a strewn field. Spirit observed two probable iron meteorites from its Winter Haven location in the Columbia Hills in Gusev Crater. Chondrites have not been identified to date, which may be a result of their lower strengths and probability to survive impact at current atmospheric pressures. Impact craters directly associated with Heat Shield Rock, Barberton, or Santa Catarina have not been observed, but such craters could have been erased by eolian-driven erosion.Additional co-authors: DW Ming, RV Morris, PA de Souza Jr, SW Squyres, C Weitz, AS Yen, J Zipfel, T Economo

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Balloon-protected carotid artery stenting: relationship of periprocedural neurological complications with the size of particulate debris

BACKGROUND: Carotid artery stenting (CAS) has been advocated as an alternative to endarterectomy. To prevent cerebral atheroembolism during CAS, distal balloon occlusion of the target artery increasingly is employed during the procedure. A correlation of the size of captured particles with the incidence of periprocedural neurological complications (PNCs) has not been attempted. METHODS AND RESULTS: In a 4-center, phase-1 trial, 54 patients (46 men; age, 69+/-8 years) underwent 58 CAS procedures using the PercuSurge GuardWire system for distal protection. Aspirated debris was sent for histological/cytological analysis. Stent placement was successful in all cases. Mean balloon occlusion time was 10.4+/-4.0 minutes (range, 3.0 to 22.0 minutes). Three patients (5.2%) experienced PNCs: 1 prolonged reversible ischemic neurological deficit that resolved in /=10 000 micrometer(2)) were found in 48 aspirates (83%). The median number of particles, their maximum diameter, and their maximum area were all significantly higher in the aspirates obtained during procedures associated with PNCs than in aspirates obtained during procedures not associated with PNCs. However, pronounced overlap in the distributions (PNCs versus no PNCs) of the number and maximum diameter of particles precluded any predictive inferences. In contrast, a maximum particle area >800 000 micrometer(2) (>0.8 mm(2)) was associated with a 60% chance of having a PNC. CONCLUSIONS: Despite balloon protection, PNCs occurred in 5.2% of patients who underwent CAS procedures. The maximum area of aspirated particles seems to be an indicator of increased risk for PNCs

Coherence properties from speckle contrast analysis at the European XFEL

We show the results of speckle contrast analysis at the MID instrument of European XFEL in the hard X-ray regime. Speckle patterns measured from static colloidal samples are compared to results previously obtained at the SPB/SFX instrument. A high degree of coherence of 0.79 is obtained by modelling the q-dependence of the speckle contrast, that corresponds to a number of coherent modes of M = 1.7. Furthermore, the variation of contrast over many pulse trains is exceptional low, resulting in a degree of coherence with a relative standard deviation below 0.1. Our results demonstrate the high stability of coherence properties at European XFEL over many X-ray pulses and pulse trains which is a prerequisite for coherence-based techniques such as MHz X-ray photon correlation spectroscopy