A Comparative Environmental Impact Analysis of Screening Tests for Colorectal Cancer.

Background: Healthcare is a major contributor to global greenhouse gas emissions. Colorectal cancer (CRC) screening is one of the most widely used healthcare services in the US, indicated for approximately 134 million adults. Recommended screening options include fecal immunochemical tests (FITs) every year, CT colonographies (CTCs) every 5 years, or colonoscopies every 10 years.

Intranasal oxytocin for apathy in people with frontotemporal dementia (FOXY): a multicentre, randomised, double-blind, placebo-controlled, adaptive, crossover, phase 2a/2b superiority trial.

Background: No treatments exist for apathy in people with frontotemporal dementia. Previously, in a randomised double-blind, placebo-controlled, dose-finding study, intranasal oxytocin administration in people with frontotemporal dementia improved apathy ratings on the Neuropsychiatric Inventory over 1 week and, in a randomised, double-blind, placebo-controlled, crossover study, a single dose of 72 IU oxytocin increased blood-oxygen-level-dependent signal in limbic brain regions. We aimed to determine whether longer treatment with oxytocin improves apathy in people with frontotemporal dementia.

Blarcamesine for the treatment of Early Alzheimer's Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial.

Background: There are no approved oral disease-modifying treatments for Alzheimer's disease (AD).

Objectives: The objective of this study was to assess efficacy and safety of blarcamesine (ANAVEX®2-73), an orally available small-molecule activator of the sigma-1 receptor (SIGMAR1) in early AD through restoration of cellular homeostasis including autophagy enhancement.

Design: ANAVEX2-73-AD-004 was a randomized, double-blind, placebo-controlled, 48-week Phase IIb/III trial.

Nanoscale flow cytometry-based quantification of blood-based extracellular vesicle biomarkers distinguishes MCI and Alzheimer's disease.

Introduction: Accurate testing for Alzheimer's disease (AD) represents a crucial step for therapeutic advancement. Currently, tests are expensive and require invasive sampling or radiation exposure.

Methods: We developed a nanoscale flow cytometry (nFC)-based assay of extracellular vesicles (EVs) to screen biomarkers in plasma from mild cognitive impairment (MCI), AD, or controls.

Co-registration of MALDI-MSI and histology demonstrates gangliosides co-localize with amyloid beta plaques in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurological condition characterized by impaired cognitive function and behavioral alterations. While AD research historically centered around mis-folded proteins, advances in mass spectrometry techniques have triggered increased exploration of the AD lipidome with lipid dysregulation emerging as a critical player in AD pathogenesis. Gangliosides are a class of glycosphingolipids enriched within the central nervous system.

Small GTPases control macropinocytosis of amyloid precursor protein and cleavage to amyloid-β.

The overproduction of the toxic peptide amyloid-beta (Aβ) generated from the cleavage of amyloid precursor protein (APP) is proposed to be a critical event in the development of Alzheimer's disease. Evidence suggests that the cleavage of APP occurs after its internalization from the cell surface. Previously, we identified a novel pathway for APP internalization, which trafficks cell surface APP directly to lysosomes by macropinocytosis, leading to its processing into Aβ.

The nonverbal expression of guilt in healthy adults.

Guilt is a negative emotion elicited by realizing one has caused actual or perceived harm to another person. One of guilt's primary functions is to signal that one is aware of the harm that was caused and regrets it, an indication that the harm will not be repeated. Verbal expressions of guilt are often deemed insufficient by observers when not accompanied by nonverbal signals such as facial expression, gesture, posture, or gaze.

Neuropsychiatric symptoms and brain morphology in patients with mild cognitive impairment, cerebrovascular disease and Parkinson disease: A cross sectional and longitudinal study.

Objectives: Neuropsychiatric symptoms (NPS) increase risk of developing dementia and are linked to various neurodegenerative conditions, including mild cognitive impairment (MCI due to Alzheimer's disease [AD]), cerebrovascular disease (CVD), and Parkinson's disease (PD). We explored the structural neural correlates of NPS cross-sectionally and longitudinally across various neurodegenerative diagnoses.

Methods: The study included individuals with MCI due to AD, (n = 74), CVD (n = 143), and PD (n = 137) at baseline, and at 2-years follow-up (MCI due to AD, n = 37, CVD n = 103, and PD n = 84).

Co-registration of MALDI-MSI and histology demonstrates gangliosides co-localize with amyloid beta plaques in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurological condition characterized by impaired cognitive function and behavioural alterations. While AD research historically centered around mis-folded proteins, advances in mass spectrometry techniques have triggered increased exploration of the AD lipidome with lipid dysregulation emerging as a critical player in AD pathogenesis. Gangliosides are a class of glycosphingolipids enriched within the central nervous system.

A methodological primer of extracellular vesicles isolation and characterization via different techniques.

We present four different protocols of varying complexity for the isolation of cell culture-derived extracellular vesicles (EVs)/exosome-enriched fractions with the objective of providing researchers with easily conducted methods that can be adapted for many different uses in various laboratory settings and locations. These protocols are primarily based on polymer precipitation, filtration and/or ultracentrifugation, as well as size-exclusion chromatography (SEC) and include: (i) polyethylene glycol and sodium chloride supplementation of the conditioned medium followed by low-speed centrifugation; (ii) ultracentrifugation of conditioned medium; (iii) filtration of conditioned media through a 100-kDa exclusion filter; and (iv) isolation using a standard commercial kit. These techniques can be followed by further purification by ultracentrifugation, sucrose density gradient centrifugation, or SEC if needed and the equipment is available.

Using Artificial Intelligence as a Melanoma Screening Tool in Self-Referred Patients.

Introduction: Early detection of melanoma requires timely access to medical care. In this study, we examined the feasibility of using artificial intelligence (AI) to flag possible melanomas in self-referred patients concerned that a skin lesion might be cancerous.

Methods: Patients were recruited for the study through advertisements in 2 hospitals in Halifax, Nova Scotia, Canada.

A unique case of glaucoma associated with heterotopic bone formation in the anterior chamber angle.

Purpose: To describe a unique case of unilateral open angle glaucoma secondary to heterotopic bone formation in the anterior chamber angle.

Observations: A 57 year-old male with an unremarkable history presented with right eye pain. Anterior segment examination demonstrated a solid, white deposit overlying the trabecular meshwork and peripheral iris associated with an intraocular pressure of 44 mmHg.

White matter hyperintensities and smaller cortical thickness are associated with neuropsychiatric symptoms in neurodegenerative and cerebrovascular diseases.

Background: Neuropsychiatric symptoms (NPS) are a core feature of most neurodegenerative and cerebrovascular diseases. White matter hyperintensities and brain atrophy have been implicated in NPS. We aimed to investigate the relative contribution of white matter hyperintensities and cortical thickness to NPS in participants across neurodegenerative and cerebrovascular diseases.

Rare neurovascular genetic and imaging markers across neurodegenerative diseases.

Introduction: Cerebral small vessel disease (SVD) is common in patients with cognitive impairment and neurodegenerative diseases such as Alzheimer's and Parkinson's. This study investigated the burden of magnetic resonance imaging (MRI)-based markers of SVD in patients with neurodegenerative diseases as a function of rare genetic variant carrier status.

Methods: The Ontario Neurodegenerative Disease Research Initiative study included 520 participants, recruited from 14 tertiary care centers, diagnosed with various neurodegenerative diseases and determined the carrier status of rare non-synonymous variants in five genes (ABCC6, COL4A1/COL4A2, NOTCH3/HTRA1).

Abscopal responses in patients with metastatic melanoma involving skin and subcutaneous tissues treated with intralesional IL2 plus BCG.

Cutaneous melanoma is relatively common with increasing incidence and significant mortality. While the mainstay of therapy is surgical, patients with stage III and IV disease fare poorer than those with early-stage disease and often benefit from adjuvant therapies. While systemic immunotherapy has changed the landscape of melanoma treatment, for some patients systemic toxicities related to these treatments prohibit successful administration or completion of therapy.

Cognitive correlates of antisaccade behaviour across multiple neurodegenerative diseases.

Oculomotor tasks generate a potential wealth of behavioural biomarkers for neurodegenerative diseases. Overlap between oculomotor and disease-impaired circuitry reveals the location and severity of disease processes via saccade parameters measured from eye movement tasks such as prosaccade and antisaccade. Existing studies typically examine few saccade parameters in single diseases, using multiple separate neuropsychological test scores to relate oculomotor behaviour to cognition; however, this approach produces inconsistent, ungeneralizable results and fails to consider the cognitive heterogeneity of these diseases.

The psychophysiology of guilt in healthy adults.

Guilt is a negative emotion, elicited by realizing one has caused actual or perceived harm to another person. Anecdotally, guilt often is described as a visceral and physical experience. However, while the way that the body responds to and contributes to emotions is well known in basic emotions, little is known about the characteristics of guilt as generated by the autonomic nervous system.

Merkel cell carcinoma: an update.

Merkel cell carcinoma (MCC) is an uncommon primary cutaneous neuroendocrine carcinoma associated with an adverse prognosis. In recent years, our understanding of MCC biology has markedly progressed. Since the discovery of the Merkel cell polyomavirus, it has become clear that MCC represents an ontogenetically dichotomous group of neoplasms with overlapping histopathology.

Plasma derived extracellular vesicle biomarkers of microglia activation in an experimental stroke model.

Chronic microglia activation post-stroke is associated with worse neurological and cognitive outcomes. However, measurement of microglia activation in vivo is currently limited. Plasma derived extracellular vesicles (EVs) are cell-specific indicators that may allow for non-invasive measurement of microglia phenotype.

Fibrinogen primes the microglial NLRP3 inflammasome and propagates pro-inflammatory signaling via extracellular vesicles: Implications for blood-brain barrier dysfunction.

The brain's response to acute injury is characterized by increased permeability of the blood-brain barrier (BBB) and pro-inflammatory microglia signaling, both of which have been linked to poor cognitive outcomes and neurological disease. The damaged BBB has increased leakiness, allowing serum proteins like fibrinogen into the brain, which interacts with local cells in a deleterious manner. At the same time, in response to injury, microglia demonstrate increased NLRP3 inflammasome activity and heightened release of pro-inflammatory cytokines.