Biomarkers.

Background: White Matter Hyperintensities (WMH) appear on T2-weighted Fluid-Attenuated Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI) and are an important biomarker of cerebral small vessel disease (CSVD), cognitive decline, and stroke. However, manual delineation is laborious and bias-prone, while automated segmentation has proven challenging. With the recent conclusion of the MICCAI-Society WMH segmentation challenge, and our large clinical trials, "Risk Reduction for Alzheimer's Disease" (rrAD) and "Hypertension, Intracranial Pulsatility and Brain Amyloid-beta Clearance in older adults" (HIPAC), we investigated the differences in the total WMH volume segmented by various algorithms to ensure the extraction of accurate and meaningful image-derived phenotypes.

Biomarkers.

Background: Extracellular vesicles (EVs) are lipid bilayer nanoparticles (30-10,000 nm) released from all cells that facilitate cell-to-cell communication. Cell type-specific EVs can be enriched using cell-specific surface markers. Neuronal-enriched EVs (NEVs) contain measurable neurotrophins, pro- and mature brain-derived neurotrophic factor (BDNF), that have opposing action in neuronal plasticity.

Alzheimer's Imaging Consortium.

Background: White Matter Hyperintensities (WMH) appear on T2-weighted Fluid-Attenuated Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI) and are an important biomarker of cerebral small vessel disease (CSVD), cognitive decline, and stroke. However, manual delineation is laborious and bias-prone, while automated segmentation has proven challenging. With the recent conclusion of the MICCAI-Society WMH segmentation challenge, and our large clinical trials, "Risk Reduction for Alzheimer's Disease" (rrAD) and "Hypertension, Intracranial Pulsatility and Brain Amyloid-beta Clearance in older adults" (HIPAC), we investigated the differences in the total WMH volume segmented by various algorithms to ensure the extraction of accurate and meaningful image-derived phenotypes.

Plasminogen activator inhibitor-1 mediates cerebral ischemia-induced astrocytic reactivity.

Although ischemia increases the abundance of plasminogen activator inhibitor-1 (PAI-1), its source and role in the ischemic brain remain unclear. We detected PAI-1-immunoreactive cells with morphological features of reactive astrocytes in the peri-ischemic cortex of mice after an experimentally-induced ischemic lesion, and of a chimpanzee that suffered a naturally-occurring stroke. We found that although the abundance of PAI-1 increases 24 hours after the onset of the ischemic injury in a non-reperfusion murine model of ischemic stroke, at that time-point there is no difference in astrocytic reactivity and the volume of the ischemic lesion between wild-type (Wt) animals and in mice either genetically deficient (PAI-1) or overexpressing PAI-1 (PAI-1).

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors.

β-Keto amides were used as convenient precursors to both 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides. The utility of this approach is demonstrated with the synthesis of fourteen novel and four known quinolone derivatives, including natural products of microbial origin such as HHQ and its C-congener. Two compounds with high activity against have been identified among the newly obtained quinolones, with MICs ≤ 3.