Publications by authors named "Lessard E"

Background: Iduronate-2-sulfatase (IDS) deficiency (MPS II; Hunter syndrome) is a disorder that exhibits peripheral and CNS pathology. The blood brain barrier (BBB) prevents systemic enzyme replacement therapy (ERT) from alleviating CNS pathology. We aimed to enable brain delivery of systemic ERT by using molecular BBB-Trojans targeting endothelial transcytosis receptors.

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Background: Peer support has been extensively studied in specific areas of community-based primary care such as mental health, substance use, HIV, homelessness, and Indigenous health. These programs are often built on the assumption that peers must share similar social identities or lived experiences of disease to be effective. However, it remains unclear how peers can be integrated in general primary care setting that serves people with a diversity of health conditions and social backgrounds.

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Eukaryotic DNA replication is accompanied by the disassembly and reassembly of nucleosomes and the transmission of epigenetic marks to the newly assembled chromatids. Several histone chaperones, including CAF-1 and Asf1p, are central to these processes. On the other hand, replication forks pause at numerous positions throughout the genome, but it is not known if and how this pausing affects the reassembly and maintenance of chromatin structures.

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Background: Compassionate communities build on health promoting palliative care that aims to address gaps in access, quality, and continuity of care in the context of dying, death, loss, and grief. While community engagement is a core principle of public health palliative care, it has received little attention in empirical studies of compassionate communities.

Objectives: The objectives of this research are to describe the process of community engagement initiated by two compassionate communities projects, to understand the influence of contextual factors on community engagement over time, and assess the contribution of community engagement on proximal outcomes and the potential for sustaining compassionate communities.

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Background: Some studies suggest that individuals having lost a loved one during the COVID-19 pandemic report higher levels of grief reactions than people bereaved from natural causes. Little is known about the lived and subjective experience of individuals who lost a loved one under confinement measures.

Aim: This research aims to provide a phenomenological description of pandemic grief (PG) that can be useful in clinical settings and bereavement services.

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Purpose: We have recently demonstrated the brain-delivery of an Amyloid-ß oligomer (Aßo)-binding peptide-therapeutic fused to the BBB-crossing single domain antibody FC5. The bi-functional fusion protein, FC5-mFc-ABP (KG207-M) lowered both CSF and brain Aß levels after systemic dosing in transgenic mouse and rat models of Alzheimer's disease (AD). For development as a human therapeutic, we have humanized and further engineered the fusion protein named KG207-H.

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Purpose: The COVID-19 pandemic has disrupted thousands of individuals' experience of caregiving and grief. This qualitative study aimed to gain in-dept understanding of family caregivers' lived experiences of caregiving and bereavement in the context of the COVID-19 pandemic in Quebec, Canada. The study also aimed at providing new insight about caregiving and bereavement by analysing the metaphors family caregivers use to report their experiences.

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biomarker abnormalities provide measures to monitor therapeutic interventions targeting amyloid-β pathology as well as its effects on downstream processes associated with Alzheimer's disease pathophysiology. Here, we applied an longitudinal study design combined with imaging and cerebrospinal fluid biomarkers, mirroring those used in human clinical trials to assess the efficacy of a novel brain-penetrating anti-amyloid fusion protein treatment in the McGill-R-Thy1-APP transgenic rat model. The bi-functional fusion protein consisted of a blood-brain barrier crossing single domain antibody (FC5) fused to an amyloid-β oligomer-binding peptide (ABP) via Fc fragment of mouse IgG (FC5-mFc2a-ABP).

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The maintenance of therapeutic glycoproteins within the circulatory system is associated, in large part, with the integrity of sialic acids as terminal sugars on the glycans. Glycoprotein desialylation, either by spontaneous cleavage or through host sialidases, leads to protein clearance, mainly through the liver. Thus, the installation of minimally modified sialic acids that are hydrolysis-resistant yet biologically equivalent should lead to increased circulatory half-lives and improved pharmacokinetic profiles.

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The insulin-like growth factor (IGF) axis has been implicated in the progression of malignant disease and identified as a clinically important therapeutic target. Several IGF-1 receptor (IGF-1R) targeting drugs including humanized monoclonal antibodies have advanced to phase II/III clinical trials, but to date, have not progressed to clinical use, due, at least in part, to interference with insulin receptor signalling. We previously reported on the production of a soluble fusion protein consisting of the extracellular domain of human IGF-1R fused to the Fc portion of human IgG (first generation IGF-TRAP) that bound human IGF-1 and IGF-2 with a 3 log higher affinity than insulin.

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Introduction: The University of California San Francisco Fresno Department of Emergency Medicine provides base hospital support for the Sequoia and Kings Canyon National Parks (SEKI) emergency medical services (EMS) system. This descriptive epidemiologic study reports reasons the park EMS system is used and interventions provided, detailing the nature of patient encounters, type and frequency of injuries and interventions, reasons for base hospital contact, and patient dispositions.

Methods: Patient charts for all EMS encounters in SEKI from 2011 to 2013 were included, and relevant data were extracted by a single reviewer.

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The blood-brain barrier (BBB) is a formidable obstacle for brain delivery of therapeutic antibodies. However, antibodies against the transferrin receptor (TfR), enriched in brain endothelial cells, have been developed as delivery carriers of therapeutic cargoes into the brain via a receptor-mediated transcytosis pathway. In vitro and in vivo studies demonstrated that either a low-affinity or monovalent binding of these antibodies to the TfR improves their release on the abluminal side of the BBB and target engagement in brain parenchyma.

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Purpose: This study investigates the potential application of image-based motion tracking and real-time motion correction to a helical tomotherapy system.

Methods: A kV x-ray imaging system was added to a helical tomotherapy system, mounted 90 degrees offset from the MV treatment beam, and an optical camera system was mounted above the foot of the couch. This experimental system tracks target motion by acquiring an x-ray image every few seconds during gantry rotation.

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Rationale And Objectives: Thoracic x-ray computed tomography (CT) and hyperpolarized He magnetic resonance imaging (MRI) provide quantitative measurements of airspace enlargement in patients with emphysema. For patients with panlobular emphysema due to alpha-1 antitrypsin deficiency (AATD), sensitive biomarkers of disease progression and response to therapy have been difficult to develop and exploit, especially those biomarkers that correlate with outcomes like quality of life. Here, our objective was to generate and compare CT and diffusion-weighted inhaled-gas MRI measurements of emphysema including apparent diffusion coefficient (ADC) and MRI-derived mean linear intercept (L) in patients with AATD, chronic obstructive pulmonary disease (COPD) ex-smokers, and elderly never-smokers.

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Purpose: We generated lung morphometry measurements using single-breath diffusion-weighted MRI and three different acinar duct models in healthy participants and patients with emphysema stemming from chronic obstructive lung disease (COPD) and alpha-1 antitrypsin deficiency (AATD).

Methods: Single-breath-inhaled He MRI with five diffusion sensitizations (b-value = 0, 1.6, 3.

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Introduction: While a nationwide poison control registry exists in Chile, reporting to the center is sporadic and happens at the discretion of the treating physician or by patients' self-report. Moreover, individual hospitals do not monitor accidental or intentional poisoning in a systematic manner. The goal of this study was to identify all cases of intentional medication overdose (MO) that occurred over two years at a large public hospital in Santiago, Chile, and examine its epidemiologic profile.

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The purpose of this study was to evaluate the performance of a commercially avail-able CyberKnife system with a multileaf collimator (CK-MLC) for stereotactic body radiotherapy (SBRT) and standard fractionated intensity-modulated radiotherapy (IMRT) applications. Ten prostate and ten intracranial cases were planned for the CK-MLC. Half of these cases were compared with clinically approved SBRT plans generated for the CyberKnife with circular collimators, and the other half were compared with clinically approved standard fractionated IMRT plans generated for conventional linacs.

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Diffusion-weighted magnetic resonance imaging (MRI) provides a way to generate in vivo lung images with contrast sensitive to the molecular displacement of inhaled gas at subcellular length scales. Here, we aimed to evaluate hyperpolarized (3)He MRI estimates of the alveolar dimensions in 38 healthy elderly never-smokers (73 ± 6 years, 15 males) and 21 elderly ex-smokers (70 ± 10 years, 14 males) with (n = 8, 77 ± 6 years) and without emphysema (n = 13, 65 ± 10 years). The ex-smoker and never-smoker subgroups were significantly different for FEV1/FVC (P = 0.

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Pre-clinical behavioral pharmacology studies supporting indications like analgesia typically consist of at least three different studies; dose-finding, duration of effect, and tolerance-development studies. Pharmacokinetic (PK) plasma samples are generally taken from a parallel group of animals to avoid disruption of the behavioral pharmacodynamic (PD) endpoint. Our objective was to investigate if pre-clinical behavioral pharmacology studies in rats could be performed effectively by combining three studies into a single experimental design and using sparse PK sampling in the same animals as for PD.

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Cannabinoid CB(1) receptor agonists exhibit potent analgesic effects in rodents and humans, but their clinical utility as analgesic drugs is often limited by centrally mediated side effects. We report herein the preparation of N-methyl-3-(tetrahydro-2H-pyran-4-yl)-2,3,4,9-tetrahydro-1H-carbazole-6-carboxamides as a novel class of hCB(1)/hCB(2) dual agonists with attractive physicochemical properties. More specifically, (R)-N,9-dimethyl-N-(4-(methylamino)-4-oxobutyl)-3-(tetrahydro-2H-pyran-4-yl)-2,3,4,9-tetrahydro-1H-carbazole-6-carboxamide, displayed an extremely low level of CNS penetration (Rat Cbr/Cplasma=0.

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An oral, peripherally restricted CB1/CB2 agonist could provide an interesting approach to treat chronic pain by harnessing the analgesic properties of cannabinoids but without the well-known central side effects. γ-Carbolines are a novel class of potent mixed CB1/CB2 agonists characterized by attractive physicochemical properties including high aqueous solubility. Optimization of the series has led to the discovery of 29, which has oral activity in a rat inflammatory pain model and limited brain exposure at analgesic doses, consistent with a lower risk of CNS-mediated tolerability issues.

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Background: The link between meat and various chronic diseases has been qualified recently, and is now accepted as being related to the amount of saturated fat present. Other work has shown differences in total lipid profiles between meat from 'wild' and 'domesticated' animals, with the 'wild' reflecting higher levels of polyunsaturated and lower saturated fat. This study assessed both meat types from South African sources.

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Background: The CCR2/CCL2 system has been identified as a regulator in the pathogenesis of neuropathy-induced pain. However, CCR2 target validation in analgesia and the mechanism underlying antinociception produced by CCR2 antagonists remains poorly understood. In this study, in vitro and in vivo pharmacological approaches using a novel CCR2 antagonist, AZ889, strengthened the hypothesis of a CCR2 contribution to neuropathic pain and provided confidence over the possibilities to treat neuropathic pain with CCR2 antagonists.

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