Publications by authors named "Bosma R"

Purpose: Pain is inherently salient and so draws our attention in addition to impacting performance on attention-demanding tasks. Individual variability in pain-attention interactions can be assessed by two kinds of behavioral phenotypes that quantify how individuals prioritize pain versus attentional needs. The intrinsic attention to pain (IAP) measure quantifies the degree to which a person attends to pain (high-IAP) or mind-wanders away from pain (low-IAP).

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A fundamental issue in neuroscience is a lack of understanding regarding the relationship between brain function and the white matter architecture that supports it. Individuals with chronic neuropathic pain (NP) exhibit functional abnormalities throughout brain networks collectively termed the "dynamic pain connectome" (DPC), including the default mode network (DMN), salience network, and ascending nociceptive and descending pain modulation systems. These functional abnormalities are often observed in a sex-dependent fashion.

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Analysis of structure-kinetic relationships (SKR) can contribute to an improved understanding of receptor-ligand interactions. Here, fragment (4-(2-benzylphenoxy)-1-methylpiperidine) was used in different fragment growing approaches to mimic the putative binding mode of the long residence time (RT) ligands olopatadine, acrivastine, and levocetirizine at the histamine H receptor (HR). SKR analyses reveal that introduction of a carboxylic acid moiety can increase RT at HR up to 11-fold.

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Background: Living with chronic pain as a young adult (YA) can impact the physical, emotional, social, cognitive, and role function domains of life. Once YAs receive care for their specialist chronic pain care they are expected to self-navigate a complex health care system to transition to community-based care (i.e.

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The perception of pain and ability to cope with it varies widely amongst people, which in part could be due to the presence of inhibitory (antinociceptive) or facilitatory (pronociceptive) effects in conditioned pain modulation (CPM). This study examined whether individual differences in CPM reflect functional connectivity (FC) strengths within nodes of the descending antinociceptive pathway (DAP). A heat-based CPM paradigm and resting-state functional magnetic resonance imaging (rs-fMRI) were used to test the hypothesis that an individual's capacity to exhibit inhibitory CPM (changes in test stimuli [TS] pain due to a conditioning stimulus [CS]) reflects FC of the subgenual anterior cingulate cortex (sgACC), periaqueductal gray (PAG), and rostral ventromedial medulla (RVM).

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Unlabelled: Chronic pain affects 1.9 billion people worldwide and wait times for interprofessional pain management programs can be extensive. The existing wait times provide an opportunity to introduce internet-based interventions that enhance self-management ability.

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Introduction: In 2011, the Canadian Institutes of Health Research launched a Strategy for Patient-Oriented Research (POR) for healthcare and academic institutions to increase patient participation in health research. POR considers patients and caregivers as partners with scientific investigators, healthcare professionals and administrative decision-makers. As POR becomes a standard worldwide, the how-to, practical aspects of POR integration in healthcare institutions remain uncharted territory.

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Tin halide perovskites are promising for optoelectronics, although their sensitivity to ambient conditions due to Sn(II) oxidation presents a challenge. Encapsulation techniques can mitigate degradation and facilitate advanced studies of the intrinsic properties. To study and improve the ambient stability of CsSnBr and CsSnI nanocrystal (NC) thin films, we explored various encapsulation methods: organic, inorganic, and hybrid.

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Objective: Chronic pain affects approximately 7.6 million Canadians and access to care remains an issue. The Power Over Pain (POP) Portal offers immediate access to evidence-based resources ranging from low- (e.

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Article Synopsis
  • A 42-year-old man experienced renal failure and ongoing fatigue after a SARS-CoV-2 infection, leading to referral to internal medicine.
  • Blood tests showed he had anemia and severe kidney issues, and further testing identified type I cryoglobulinemia with antibodies targeting SARS-CoV-2.
  • The patient's symptoms and lab results improved over three months, suggesting that COVID-19 induced cryoglobulinemia is typically mild and resolves on its own after the viral infection clears.
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  • Atypical Chemokine Receptor 3 (ACKR3) is a G protein-coupled receptor that does not activate G proteins, and its activation mechanism is not well understood.
  • Researchers used advanced techniques like mass spectrometry and molecular dynamics simulations to investigate how different ligands interact with ACKR3.
  • The study revealed that certain structural changes within the receptor, particularly in specific helices and loops, dictate its activation or inhibition, and identified binding sites that help explain its unique dynamic characteristics.
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  • Individuals on hemodialysis are at a higher risk for malnutrition, but using subjective global assessment (SGA) for diagnosis is time-consuming.
  • This study compared the effectiveness of the Canadian Nutrition Screening Tool (CNST) and the Geriatric Nutrition Risk Index (GNRI) in identifying malnutrition risk among 95 hemodialysis patients through a review of medical charts.
  • Results showed that both screening tools had low sensitivity (20% for CNST and 35% for GNRI), indicating they are not effective at accurately detecting malnutrition risk in this population, leading to the conclusion that further research is needed for better tools.
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This study introduces (S)-Opto-prop-2, a second-generation photoswitchable ligand designed for precise modulation of β-adrenoceptor (βAR). Synthesised by incorporating an azobenzene moiety with propranolol, (S)-Opto-prop-2 exhibited a high PSS (photostationary state for cis isomer) percentage (∼90 %) and a favourable half-life (>10 days), facilitating diverse bioassay measurements. In vitro, the cis-isomer displayed substantially higher βAR binding affinity than the trans-isomer (1000-fold), making (S)-Opto-prop-2 one of the best photoswitchable GPCR (G protein-coupled receptor) ligands reported so far.

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Background: Chronic pain is a complex disease that requires interprofessional care for effective management. Despite the need for multidisciplinary care, disease and health care inequities can prevent individuals from attaining adequate treatment. Factors such as mental health, cost, and distance to a health care center can contribute to health care accessibility inequality.

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NanoLuc-mediated bioluminescence resonance energy transfer (NanoBRET) has gained popularity for its ability to homogenously measure ligand binding to G protein-coupled receptors (GPCRs), including the subfamily of chemokine receptors. These receptors, such as ACKR3, CXCR4, CXCR3, play a crucial role in the regulation of the immune system, are associated with inflammatory diseases and cancer, and are seen as promising drug targets. The aim of this study was to optimize NanoBRET-based ligand binding to NLuc-ACKR3 and NLuc-CXCR4 using different fluorescently labeled chemokine CXCL12 analogs and their use in a multiplex NanoBRET binding assay of two chemokine receptors at the same time.

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Neuropathic pain (NP) is a prevalent condition often associated with heightened pain responsiveness suggestive of central sensitization. Neuroimaging biomarkers of treatment outcomes may help develop personalized treatment strategies, but white matter (WM) properties have been underexplored for this purpose. Here we assessed whether WM pathways of the default mode network (DMN: medial prefrontal cortex [mPFC], posterior cingulate cortex, and precuneus) and descending pain modulation system (periaqueductal gray [PAG]) are associated with ketamine analgesia and attenuated temporal summation of pain (TSP, reflecting central sensitization) in NP.

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Article Synopsis
  • - The study discusses the implementation of a Single-Entry Model (SEM) for managing chronic pain referrals across seven hospitals in Toronto to improve patient access and coordination of care over a six-year period.
  • - Following the SEM's introduction in 2017, there was a significant increase in referrals (93% rise) and providers (91% rise), while average wait times for chronic pain services decreased from about 299 days to 176 days.
  • - Despite the overall improvements, some specific pain conditions like chronic pelvic pain and fibromyalgia still face long wait times, suggesting a need for ongoing assessment and refinement of care in these areas.
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Atypical chemokine receptor 3 (ACKR3), formerly referred to as CXCR7, is considered to be an interesting drug target. In this study, we report on the synthesis, pharmacological characterization and radiolabeling of VUF15485, a new ACKR3 small-molecule agonist, that will serve as an important new tool to study this -arrestin-biased chemokine receptor. VUF15485 binds with nanomolar affinity (pIC = 8.

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Background: Persistent pelvic pain is pain sensed in or around the pelvis and is often associated with negative cognitive, behavioral, sexual, and emotional consequences. The lack of interprofessional persistent pelvic pain management programs that address the complex interplay of biopsychosocial factors result in lengthy wait times and negative health outcomes. Limited access to evidence informed self-management educational resources contributes to poor coping strategies.

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Article Synopsis
  • A 39-year-old woman diagnosed with relapsing nephrotic syndrome was found to have cryofibrinogen and a monoclonal immunoglobulin (M-protein) in her blood, indicating monoclonal gammopathy related to kidney issues.
  • Initial immunosuppressive treatment led to temporary improvement, but after her condition relapsed, she underwent more intensive therapy, including stem cell transplantation, which again provided temporary relief.
  • Subsequent experiments revealed that the cryoactivity was dependent on the M-protein, suggesting that cryofibrinogenemia is linked to this protein and should be associated with monoclonal gammopathy of renal significance.
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Resilience is an important personal characteristic that influences health and recovery. Previous studies of chronic pain suggest that highly resilient people may be more effective at modulating their pain. Since brain gray matter in the antinociceptive pathway has also been shown to be abnormal in people with chronic pain, we examined whether resilience is related to gray matter in regions of interest (ROIs) of the antinociceptive pathway (rostral and subgenual anterior cingulate cortex (rACC, sgACC), anterior insula (aINS), dorsolateral prefrontal cortex (dlPFC)) normally and in people who are experiencing chronic pain.

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The therapeutic potential of ligands targeting disease-associated membrane proteins is predicted by ligand-receptor binding constants, which can be determined using NanoLuciferase (NanoLuc)-based bioluminescence resonance energy transfer (NanoBRET) methods. However, the broad applicability of these methods is hampered by the restricted availability of fluorescent probes. We describe the use of antibody fragments, like nanobodies, as universal building blocks for fluorescent probes for use in NanoBRET.

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Two behavioural phenotypes in healthy people have been delineated based on their intrinsic attention to pain (IAP) and whether their reaction times (RT) during a cognitively-demanding task are slower (-type) or faster (A-type) during experimental pain. These behavioural phenotypes were not previously studied in chronic pain populations to avoid using experimental pain in a chronic pain context. Since pain rumination (PR) may serve as a supplement to IAP without needing noxious stimuli, we attempted to delineate A-P/IAP behavioural phenotypes in people with chronic pain and determined if PR can supplement IAP.

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Objectives: Chronic pain is highly prevalent and a leading cause of disability. Long wait times for interprofessional care provide an opportunity to introduce web-based interventions that improve psychosocial function and patients' readiness and ability to manage their condition. Here we describe the process of partnering with people with lived experience (PWLE) to develop an online self-management program enhanced by motivational interviewing.

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Carpal tunnel syndrome is the most common entrapment neuropathy and is associated with altered brain function and structure. However, little is understood of the central mechanisms associated with its pain, symptom presentation, and treatment-related resolution. This longitudinal study evaluated carpal tunnel syndrome-related alterations in brain network communication and relationships to behavioural signs of central sensitization before and after carpal tunnel release surgery.

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