Association of Ultrasonography and MRI Findings with Stroke Recurrence: Differences Between Patients with Past Histories of Atherothrombotic Versus Lacunar Infarctions.

OBJECTIVE: This study investigated the association of MRI and ultrasonography findings with stroke recurrence in patients with past histories of atherothrombotic infarctions (ATIs) or lacunar infarctions (LIs). METHODS: We prospectively analyzed the incidence of stroke recurrence. Deep and lobar cerebral microbleeds (MBs), asymptomatic lacunae, asymptomatic intracerebral hemorrhages (ICHs), severe white matter lesions (WML), and intima-media thickness (IMT) were investigated on enrollment. Stroke recurrence rates were compared by using the log-rank test. The odds ratios for recurrent strokes were derived using multivariate logistic regression models, adjusted for risk factors. RESULTS: We evaluated the stroke recurrence rate in 362 ATI patients and 309 LI patients. The log-rank test and multivariate analyses revealed that the incidence of recurrent stroke was significantly higher in ATI patients with mean IMT greater than or equal to 1.1 mm, asymptomatic ICHs, or lobar MBs than in those without. The incidence was significantly higher in LI patients with asymptomatic ICHs, asymptomatic LIs, and severe WMLs than in those without. In ATI patients, those with strictly lobar MBs or mixed MBs (deep and lobar MBs) had significantly higher recurrence rates than those without MB. In LI patients, those with strictly deep MBs or mixed MBs had higher recurrence rates than those without MB, and the incidences of those with mixed MBs was larger than those with strictly deep MBs. CONCLUSIONS: There were differences between ATI and LI patients in terms of the association of MRI and ultrasonography findings, in particularly strictly lobar or deep MBs, with the incidence of stroke recurrence.

Cerebral microbleeds and white matter hyperintensities in cardioembolic stroke patients due to atrial fibrillation: single-centre longitudinal study.

Cerebral microbleeds (CMBs) are a potential predictor of future stroke risk with clinical relevance for antithrombotic treatments, especially in ischaemic stroke patients with atrial fibrillation. However, prospective data on CMBs and risk of stroke in this particular stroke population remain scarce. We therefore performed a single centre longitudinal study to investigate CMBs and white matter hyperintensities (WMH) and the risk of future stroke. Consecutive acute stroke patients, admitted during 2008-2012 for presumed cardioembolic stroke due to non-valvular atrial fibrillation with available follow-up for the occurrence of recurrent stroke were included in our study. The rate of future stroke between patients with vs. without CMBs and moderate to severe WMH at baseline MRI was compared in separate survival and multivariable Cox regression analyses. A total of 119 cardioembolic stroke patients (49% female, median age: 76; IQR: 68-82years) were included. CMBs were found at baseline in 26/119 (21.8%; 95% CI: 14.8-30.4%) patients. Moderate to severe WMH were present in 27/119 (22.7%; 95% CI: 15.5-31.3%) cases. During a median follow-up time of 17months (IQR: 3-50months), 17 of 119 patients experienced a symptomatic stroke: 14 patients had an ischaemic stoke and 3 had intracerebral haemorrhage. The overall incidence rate for ischaemic stroke and intracerebral haemorrhage was 4.2 (95% CI: 2.3-7.1) and 0.9 (95% CI: 0.5-2.6) per 1000 patient-year of follow-up respectively. In multivariable Cox regression analysis the hazard ratio for total CMB number and the risk of stroke during follow-up was 1.05 (95% CI: 0.99-1.11; p=0.137, per each additional CMB increase), after adjusting for CHAD2S. A similar regression analysis demonstrated that moderate to severe WMHs were independently associated with increased risk of symptomatic stroke at follow-up, after adjusting for CHAD2S (HR: 2.99; 95% CI: 1.01-8.30; p=0.036). Despite the small sample size, our study provides useful data to guide power calculations and likely effect sizes relevant for ongoing and future larger studies and clinical trials.

The Severity of White Matter Lesions Possibly Influences Stroke Recurrence in Patients with Histories of Lacunar Infarctions.

BACKGROUND: To investigate the recurrent stroke types associated with white matter lesions (WMLs), we prospectively observed recurrences in patients with histories of lacunar infarctions (LIs). METHODS: We prospectively analyzed the types of stroke recurrences in 305 patients (138 women, 70.2 ± 11.7 years old) consecutively admitted to our hospital with LIs from April 2004 to December 2011. WMLs were graded using Fazekas' grades (Gr). Recurrence-free rate curves were generated by the Kaplan-Meier method using the log-rank test. RESULTS: The follow-up period was 50.7 ± 32.8 (.25-114) months. During this period, 62 strokes recurred. The incidences of strokes (all types), LIs, and deep intracerebral hemorrhages (ICHs) presenting as recurrences in 112 patients with Gr 2-3 were 6.2, 2.0, and 1.5 %/year, respectively, values that were significantly greater than those seen in 79 patients with Gr 0 (2.1 [P = .0001], .6 [P = .014], and .5 %/year [P = .016], respectively), and in 114 patients with Gr 1 (2.8 [P = .003], .9 [P = .009], and .6 %/year [P = .043], respectively). There was no significant difference among Gr 0, 1, and 2-3 in incidences of recurrences presenting as lobar ICHs, atherothrombotic infarctions, or cardioembolic infarctions. Multivariate analyses demonstrated that Gr 2-3 significantly and independently elevated the rate of deep ICHs or LIs presenting as recurrences after adjustment for risk factors. CONCLUSIONS: The presence of high-grade WMLs elevated the rate of stroke recurrences presenting as LIs and deep ICHs, but not other types.

Structure of a peptide adsorbed on graphene and graphite.

Noncovalent functionalization of graphene using peptides is a promising method for producing novel sensors with high sensitivity and selectivity. Here we perform atomic force microscopy, Raman spectroscopy, infrared spectroscopy, and molecular dynamics simulations to investigate peptide-binding behavior to graphene and graphite. We studied a dodecamer peptide identified with phage display to possess affinity for graphite. Optical spectroscopy reveals that the peptide forms secondary structures both in powder form and in an aqueous medium. The dominant structure in the powder form is α-helix, which undergoes a transition to a distorted helical structure in aqueous solution. The peptide forms a complex reticular structure upon adsorption on graphene and graphite, having a helical conformation different from α-helix due to its interaction with the surface. Our observation is consistent with our molecular dynamics calculations, and our study paves the way for rational functionalization of graphene using biomolecules with defined structures and, therefore, functionalities.

Single domain antibody templated nanoparticle resistors for sensing.

The diversity of biomolecules enables materials to be synthesized at ambient conditions into complex shapes and structures while affording improved control over nanoparticle synthesis, structures, properties, and functionality. Also, biomolecules can impart recognition and sensing capabilities to metal nanoparticles. Here, llama single domain antibodies selected towards the beta-subunit of cholera toxin were used to template the synthesis of gold nanoparticles and subsequently assembled onto electrodes via dielectrophoresis. These assemblies were then tested for the detection of cholera toxin via changes in the conductance of antibody coated gold nanoparticles.

Carbon Nanotubes for Electronic and Electrochemical Detection of Biomolecules.

The unique electronic and optical properties of carbon nanotubes, in conjunction with their size and mechanically robust nature, make these nanomaterials crucial to the development of next-generation biosensing platforms. In this Review, we present recent innovations in carbon nanotube-assisted biosensing technologies, such as DNA-hybridization, protein-binding, antibody-antigen and aptamers. Following a brief introduction on the diameter- and chirality-derived electronic characteristics of single-walled carbon nanotubes, the discussion is focused on the two major schemes for electronic biodetection, namely biotransistor- and electrochemistry-based sensors. Key fabrication methodologies are contrasted in light of device operation and performance, along with strategies for amplifying the signal while minimizing nonspecific binding. This Review is concluded with a perspective on future optimization based on array integration as well as exercising a better control in nanotube structure and biomolecular integration.

Protein immunosensor using single-wall carbon nanotube forests with electrochemical detection of enzyme labels.

Vertically aligned arrays of single-wall carbon nanotubes (SWNT forests) on pyrolytic graphite surfaces were developed for amperometric enzyme-linked immunoassays. Improved fabrication of these SWNT forests utilizing aged nanotube dispersions provided higher nanotube density and conductivity. Biosensor performance enhancement was monitored using nanotube-bound peroxidase enzymes showing a 3.5-fold better sensitivity for H2O2 than when using fresh nanotubes to assemble the forests, and improved detection limits. Absence of improvements by electron mediation for detection of H2O2 suggested very efficient electron exchange between nanotubes and enzymes attached to their ends. Protein immunosensors were made by attaching antibodies to the carboxylated ends of nanotube forests. Utilizing casein/detergent blocking to minimize non-specific binding, a detection limit of 75 pmol mL(-1) (75 nM) was achieved for human serum albumin (HSA) in unmediated sandwich immunosensors using horseradish peroxidase (HRP) labels. Mediation of the immunosensors dramatically lowered the detection limit to 1 pmol mL(-1) (1 nM), providing significantly better performance than alternative methods. In the immunosensor case, the average distance between HRP labels and nanotube ends is presumably too large for efficient direct electron exchange, but this situation can be overcome by electron mediation.

Mediated amperometric immunosensing using single walled carbon nanotube forests.

A prototype amperometric immunosensor was evaluated based on the adsorption of antibodies onto perpendicularly oriented assemblies of single wall carbon nanotubes called SWNT forests. The forests were self-assembled from oxidatively shortened SWNTs onto Nafion/iron oxide coated pyrolytic graphite electrodes. The nanotube forests were characterized using atomic force microscopy and resonance Raman spectroscopy. Anti-biotin antibody strongly adsorbed to the SWNT forests. In the presence of a soluble mediator, the detection limit for horseradish peroxidase (HRP) labeled biotin was 2.5 pmol ml(-1) (2.5 nM). Unlabelled biotin was detected in a competitive approach with a detection limit of 16 nmol ml(-1) (16 microM) and a relative standard deviation of 12%. The immunosensor showed low non-specific adsorption of biotin-HRP (approx. 0.1%) when blocked with bovine serum albumin. This immunosensing approach using high surface area, patternable, conductive SWNT assemblies may eventually prove useful for nano-biosensing arrays.