Biomarkers.

Background: There is a strong link between tau and progression of Alzheimer's disease (AD), necessitating an understanding of tau spreading mechanisms. Prior research, predominantly in typical AD, suggested that tau propagates from epicenters (regions with earliest tau) to functionally connected regions. However, given the constrained spatial heterogeneity of tau in typical AD, validating this connectivity-based tau spreading model in AD variants with distinct tau deposition patterns is crucial.

Alzheimer's Imaging Consortium.

Background: There is a strong link between tau and progression of Alzheimer's disease (AD), necessitating an understanding of tau spreading mechanisms. Prior research, predominantly in typical AD, suggested that tau propagates from epicenters (regions with earliest tau) to functionally connected regions. However, given the constrained spatial heterogeneity of tau in typical AD, validating this connectivity-based tau spreading model in AD variants with distinct tau deposition patterns is crucial.

Self-reported hearing loss is associated with faster cognitive and functional decline but not diagnostic conversion in the ADNI cohort.

Introduction: Hearing loss is identified as one of the largest modifiable risk factors for cognitive impairment and dementia. Studies evaluating this relationship have yielded mixed results.

Methods: We investigated the longitudinal relationship between self-reported hearing loss and cognitive/functional performance in 695 cognitively normal (CN) and 941 participants with mild cognitive impairment (MCI) enrolled in the Alzheimer's Disease Neuroimaging Initiative.

Validation of a Simplified Tissue-to-Reference Ratio Measurement Using SUVR to Assess Synaptic Density Alterations in Alzheimer Disease with [C]UCB-J PET.

Simplified methods of acquisition and quantification would facilitate the use of synaptic density imaging in multicenter and longitudinal studies of Alzheimer disease (AD). We validated a simplified tissue-to-reference ratio method using SUV ratios (SUVRs) for estimating synaptic density with [C]UCB-J PET. Participants included 31 older adults with AD and 16 with normal cognition.

Making assessment a team sport: a qualitative study of facilitated group feedback in internal medicine residency.

Purpose: Competency-based medical education relies on feedback from workplace-based assessment (WBA) to direct learning. Unfortunately, WBAs often lack rich narrative feedback and show bias towards Medical Expert aspects of care. Building on research examining interactive assessment approaches, the Queen's University Internal Medicine residency program introduced a facilitated, team-based assessment initiative ("Feedback Fridays") in July 2017, aimed at improving holistic assessment of resident performance on the inpatient medicine teaching units.

Key Roles of CACNA1C/Cav1.2 and CALB1/Calbindin in Prefrontal Neurons Altered in Cognitive Disorders.

Importance: The risk of mental disorders is consistently associated with variants in CACNA1C (L-type calcium channel Cav1.2) but it is not known why these channels are critical to cognition, and whether they affect the layer III pyramidal cells in the dorsolateral prefrontal cortex that are especially vulnerable in cognitive disorders.

Objective: To examine the molecular mechanisms expressed in layer III pyramidal cells in primate dorsolateral prefrontal cortices.

Synaptic density patterns in early Alzheimer's disease assessed by independent component analysis.

Synaptic loss is a primary pathology in Alzheimer's disease and correlates best with cognitive impairment as found in studies. Previously, we observed reductions of synaptic density with [C]UCB-J PET (radiotracer for synaptic vesicle protein 2A) throughout the neocortex and medial temporal brain regions in early Alzheimer's disease. In this study, we applied independent component analysis to synaptic vesicle protein 2A-PET data to identify brain networks associated with cognitive deficits in Alzheimer's disease in a blinded data-driven manner.

Creation of Porous, Perfusable Microtubular Networks for Improved Cell Viability in Volumetric Hydrogels.

The creation of large, volumetric tissue-engineered constructs has long been hindered due to the lack of effective vascularization strategies. Recently, 3D printing has emerged as a viable approach to creating vascular structures; however, its application is limited. Here, we present a simple and controllable technique to produce porous, free-standing, perfusable tubular networks from sacrificial templates of polyelectrolyte complex and coatings of salt-containing citrate-based elastomer poly(1,8-octanediol--citrate) (POC).

Assessment of disparities in timely diagnosis and comprehensive workup of cognitive impairment between English and Spanish speakers.

Background: Previous studies have examined disparities in dementia care that affect the U.S. Hispanic/Latino population, including clinician bias, lack of cultural responsiveness, and less access to health care.

A pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer's disease.

Background: Effective, disease-modifying therapeutics for the treatment of Alzheimer's disease (AD) remain a large unmet need. Extensive evidence suggests that amyloid beta (Aβ) is central to AD pathophysiology, and Aβ oligomers are among the most toxic forms of Aβ. CT1812 is a novel brain penetrant sigma-2 receptor ligand that interferes with the binding of Aβ oligomers to neurons.

Microsphere-Enabled Modular Formation of Miniaturized In Vitro Breast Cancer Models.

In search of effective therapeutics for breast cancers, establishing physiologically relevant in vitro models is of great benefit to facilitate the clinical translation. Despite extensive progresses, it remains to develop the tumor models maximally recapturing the key pathophysiological attributes of their native counterparts. Therefore, the current study aimed to develop a microsphere-enabled modular approach toward the formation of in vitro breast tumor models with the capability of incorporating various selected cells while retaining spatial organization.

Assessment of Gray Matter Microstructure and Synaptic Density in Alzheimer's Disease: A Multimodal Imaging Study With DTI and SV2A PET.

Objective: Multimodal imaging techniques have furthered our understanding of how different aspects of Alzheimer's disease (AD) pathology relate to one another. Diffusion tensor imaging (DTI) measures such as mean diffusivity (MD) may be a surrogate measure of the changes in gray matter structure associated with AD. Positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A) has been used to quantify synaptic loss, which is the major pathological correlate of cognitive impairment in AD.

Principal component analysis of synaptic density measured with [C]UCB-J PET in early Alzheimer's disease.

Background: Synaptic loss is considered an early pathological event and major structural correlate of cognitive impairment in Alzheimer's disease (AD). We used principal component analysis (PCA) to identify regional patterns of covariance in synaptic density using [C]UCB-J PET and assessed the association between principal components (PC) subject scores with cognitive performance.

Methods: [C]UCB-J binding was measured in 45 amyloid + participants with AD and 19 amyloid- cognitively normal participants aged 55-85.

Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [ C]UCB-J.

Introduction: For 30 years synapse loss has been referred to as the major pathological correlate of cognitive impairment in Alzheimer's disease (AD). However, this statement is based on remarkably few patients studied by autopsy or biopsy. With the recent advent of synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) imaging, we have begun to evaluate the consequences of synaptic alterations in vivo.

Association of entorhinal cortical tau deposition and hippocampal synaptic density in older individuals with normal cognition and early Alzheimer's disease.

Sites of early neuropathologic change provide important clues regarding the initial clinical features of Alzheimer's disease (AD). We have shown significant reductions in hippocampal synaptic density in participants with AD, consistent with the early degeneration of entorhinal cortical (ERC) cells that project to hippocampus via the perforant path. In this study, [C]UCB-J binding to synaptic vesicle glycoprotein 2A (SV2A) and [F]flortaucipir binding to tau were measured via PET in 10 participants with AD (5 mild cognitive impairment, 5 mild dementia) and 10 cognitively normal participants.

Generation of synthetic PET images of synaptic density and amyloid from F-FDG images using deep learning.

Purpose: Positron emission tomography (PET) imaging with various tracers is increasingly used in Alzheimer's disease (AD) studies. However, access to PET scans using new or less-available tracers with sophisticated synthesis and short half-life isotopes may be very limited. Therefore, it is of great significance and interest in AD research to assess the feasibility of generating synthetic PET images of less-available tracers from the PET image of another common tracer, in particular F-FDG.

Microchannels Are an Architectural Cue That Promotes Integration and Vascularization of Silk Biomaterials in Vivo.

Functional integration of implanted biomaterials and bioengineered tissues in vivo requires effective and timely vascular ingrowth. While many vascularization strategies rely on delivery of angiogenic growth factors or endothelial cells to promote vascular ingrowth, the effect of physical and architectural features of biomaterials on the vascularization process is less well understood. Microchannels are a simple, accessible architectural feature frequently engineered into 3D biomaterials to promote mass transfer.

Association of Aβ deposition and regional synaptic density in early Alzheimer's disease: a PET imaging study with [C]UCB-J.

Background: Attempts to associate amyloid-β (Aβ) pathogenesis with synaptic loss in Alzheimer's disease (AD) have thus far been limited to small numbers of postmortem studies. Aβ plaque burden is not well-correlated with indices of clinical severity or neurodegeneration-at least in the dementia stage-as deposition of Aβ reaches a ceiling. In this study, we examined in vivo the association between fibrillar Aβ deposition and synaptic density in early AD using positron emission tomography (PET).

Rectal foreign bodies: national outcomes after the operating room.

Purpose: Rectal foreign bodies can pose a unique problem to the acute care surgeon or emergency room physician. Little data exists on the patient with such a diagnosis, outside of case reports, and institutional cohorts. This study describes demographics and outcomes for this patient population.

In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET.

Introduction: Synaptic loss is a robust and consistent pathology in Alzheimer's disease (AD) and the major structural correlate of cognitive impairment. Positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A) has emerged as a promising biomarker of synaptic density.

Methods: We measured SV2A binding in 34 participants with early AD and 19 cognitively normal (CN) participants using [ C]UCB-J PET and a cerebellar reference region for calculation of the distribution volume ratio.