The dental COVID-19 paradox: Disparity in behaviors inside and outside dental schools in Canada.

OBJECTIVE: To describe the personal and professional behavior and assess the perceptions of protection and fear of contracting coronavirus disease 2019 (COVID-19) among faculty, staff, and students from all 10 Canadian dental schools during the second year of the pandemic. METHOD: Participants from a Pan-Canadian prospective study answered monthly questionnaires about their activities between April 2021 and March 2022. In May 2022, additional questions were asked about their perception of protection, fear of infection, and instances of COVID-19 testing. RESULTS: Six hundred participants were initially recruited. Over time, the participants spent less time at home and increased their participation in indoor social activities, a trend influenced by the fluctuations in COVID-19 cases (ß = â€’0.02). Over 90% of the participants were fully vaccinated, which decreased their fear of contracting the virus (χ2[4, 241‒243] = 196.07, p < 0.0001). Yet, their attitude toward protective measures did not change, and they followed them within school. CONCLUSIONS: This work shows a paradoxical behavior among dental students, staff, and faculty members in Canadian dental schools. While factors such as the vaccine's limited efficacy and a desire to protect others may contribute to stringent protective behaviors within dental schools, the mandatory nature of these measures was likely the primary motivator for the compliance. Despite potential efforts to minimize exposure to the virus during risk periods and the frequent COVID-19 testing, this paradoxical behavior raises questions about professional responsibilities extending beyond the workplace. Thus, dental schools should incorporate education about the rationale behind following different protocols and the potential consequences of outside school behaviors.

Naïve Huntington's disease microglia mount a normal response to inflammatory stimuli but display a partially impaired development of innate immune tolerance that can be counteracted by ganglioside GM1.

Chronic activation and dysfunction of microglia have been implicated in the pathogenesis and progression of many neurodegenerative disorders, including Huntington's disease (HD). HD is a genetic condition caused by a mutation that affects the folding and function of huntingtin (HTT). Signs of microglia activation have been observed in HD patients even before the onset of symptoms. It is unclear, however, whether pro-inflammatory microglia activation in HD results from cell-autonomous expression of mutant HTT, is the response of microglia to a diseased brain environment, or both. In this study, we used primary microglia isolated from HD knock-in (Q140) and wild-type (Q7) mice to investigate their response to inflammatory conditions in vitro in the absence of confounding effects arising from brain pathology. We show that naïve Q140 microglia do not undergo spontaneous pro-inflammatory activation and respond to inflammatory triggers, including stimulation of TLR4 and TLR2 and exposure to necrotic cells, with similar kinetics of pro-inflammatory gene expression as wild-type microglia. Upon termination of the inflammatory insult, the transcription of pro-inflammatory cytokines is tapered off in Q140 and wild-type microglia with similar kinetics. However, the ability of Q140 microglia to develop tolerance in response to repeated inflammatory stimulations is partially impaired in vitro and in vivo, potentially contributing to the establishment of chronic neuroinflammation in HD. We further show that ganglioside GM1, a glycosphingolipid with anti-inflammatory effects on wild-type microglia, not only decreases the production of pro-inflammatory cytokines and nitric oxide in activated Q140 microglia, but also dramatically dampen microglia response to re-stimulation with LPS in an experimental model of tolerance. These effects are independent from the expression of interleukin 1 receptor associated kinase 3 (Irak-3), a strong modulator of LPS signaling involved in the development of innate immune tolerance and previously shown to be upregulated by immune cell treatment with gangliosides. Altogether, our data suggest that external triggers are required for HD microglia activation, but a cell-autonomous dysfunction that affects the ability of HD microglia to acquire tolerance might contribute to the establishment of neuroinflammation in HD. Administration of GM1 might be beneficial to attenuate chronic microglia activation and neuroinflammation.

Fractalkine enhances oligodendrocyte regeneration and remyelination in a demyelination mouse model.

Demyelinating disorders of the central nervous system (CNS) occur when myelin and oligodendrocytes are damaged or lost. Remyelination and regeneration of oligodendrocytes can be achieved from endogenous oligodendrocyte precursor cells (OPCs) that reside in the adult CNS tissue. Using a cuprizone mouse model of demyelination, we show that infusion of fractalkine (CX3CL1) into the demyelinated murine brain increases de novo oligodendrocyte formation and enhances remyelination in the corpus callosum and cortical gray matter. This is achieved by increased OPC proliferation in the cortical gray matter as well as OPC differentiation and attenuation of microglia/macrophage activation both in corpus callosum and cortical gray matter. Finally, we show that activated OPCs and microglia/macrophages express fractalkine receptor CX3CR1 in vivo, and that in OPC-microglia co-cultures fractalkine increases in vitro oligodendrocyte differentiation by modulating both OPC and microglia biology. Our results demonstrate a novel pro-regenerative role of fractalkine in a demyelinating mouse model.

Infection Prevention Strategies Concordance in Canadian Dental Schools During the COVID-19 Pandemic.

OBJECTIVE: The aim of this research was to identify variation in specific infection prevention and control (IPC) strategies across all dental schools in Canada and to evaluate the concordance concerning COVID-19 pandemic-related IPC strategies reported by clinic directors or IPC officers (CDs/IPCOs) and those reported by students, staff, and faculty in the schools. METHOD: A cross-sectional analysis within a prospective cohort study. Participants in the cohort study reported IPC strategies used in their schools during April or May 2021. Independently, CDs/IPCOs reported IPC strategies in school protocols in July 2021. RESULTS: Of the 600 participants recruited, 332 participants who were involved in the provision of in-person dental care were further analysed. Of the 16 IPC strategies investigated, only 3 were reported by CDs/IPCOs to be used at all schools, and another 8 strategies were used by 8 or 9 of 10 or by 1 of 10 schools, indicating that concordance across schools was good for 11 of 16 strategies. Agreement between study participants and the CDs/IPCOs varied considerably by strategy (ranging between 50% and 100%) and by school (ranging between 42.9% and 97.2%). The strategies with the highest mean agreement percentage across schools were "screening or interviewing patients before appointment for COVID-19-related symptoms" (92.7%) and "checking the temperature of the staff members at least once a day using a thermometer" (91.5%). CONCLUSIONS: The level of agreement in the use of strategies between participants working in clinics and CDs/IPCOs varied considerably by strategy and by school. Given the low COVID-19 infection rates in dental schools and the reported differences in IPC protocols, key strategies should be identified. During the pandemic, IPC protocols in Canadian dental schools evolved rapidly. Comparing different strategies might help develop a unified standard IPC protocol.

The role of educators, mentors, and motivation in shaping dental students to become life-long learners: A pan-Canadian survey.

PURPOSE: The core values taught in dental school will arguably stay with the student for their whole career. An instructor has the power to influence a student's education through guidance, mentorship, and encouragement. This influence could be the factor that determines whether a student will become a motivated practitioner. The aim of this study was to identify whether dental schools are providing motivation to students to excel in their career and to become life-long learners. METHODS: A web-based questionnaire was distributed electronically during 2020-2021 to Canadian dental students via email, social media, etc. The questionnaire included questions on demographics, the dental school environment, instructor evaluation, and dental student perspectives on education. RESULTS: Of the 318 participants, 95.7% indicated their school follows a pass/fail system in some to all courses. Note that 61.2% found didactic components were weighted more heavily than clinical components. A greater number of participants found that their clinical instructors were more invested than their didactic instructors, in seeing their students become successful (53.0%) and excellent (44.6%) in their future careers. A total of 84.7% have not found a mentor, and 76% are not interested. Most participants indicated they are "moderately" motivated by their instructors to take continuing education courses (41.3%) and "not at all" motivated to continue their studies in a hospital (42.1%) or speciality residency program (56.3%). CONCLUSIONS: Instructors, educators, and mentors play a vital role in shaping dental student motivation in didactic and clinical courses, and beyond the school environment. Teaching institutions should incorporate opportunities for mentorship and student feedback to improve the delivery of dental education. Further studies may include assessing the role of mentorship at dental schools.

Anti-inflammatory role of GM1 and other gangliosides on microglia.

BACKGROUND: Gangliosides are glycosphingolipids highly enriched in the brain, with important roles in cell signaling, cell-to-cell communication, and immunomodulation. Genetic defects in the ganglioside biosynthetic pathway result in severe neurodegenerative diseases, while a partial decrease in the levels of specific gangliosides was reported in Parkinson's disease and Huntington's disease. In models of both diseases and other conditions, administration of GM1-one of the most abundant gangliosides in the brain-provides neuroprotection. Most studies have focused on the direct neuroprotective effects of gangliosides on neurons, but their role in other brain cells, in particular microglia, is not known. In this study we investigated the effects of exogenous ganglioside administration and modulation of endogenous ganglioside levels on the response of microglia to inflammatory stimuli, which often contributes to initiation or exacerbation of neurodegeneration. METHODS: In vitro studies were performed using BV2 cells, mouse, rat, and human primary microglia cultures. Modulation of microglial ganglioside levels was achieved by administration of exogenous gangliosides, or by treatment with GENZ-123346 and L-t-PDMP, an inhibitor and an activator of glycolipid biosynthesis, respectively. Response of microglia to inflammatory stimuli (LPS, IL-1ß, phagocytosis of latex beads) was measured by analysis of gene expression and/or secretion of pro-inflammatory cytokines. The effects of GM1 administration on microglia activation were also assessed in vivo in C57Bl/6 mice, following intraperitoneal injection of LPS. RESULTS: GM1 decreased inflammatory microglia responses in vitro and in vivo, even when administered after microglia activation. These anti-inflammatory effects depended on the presence of the sialic acid residue in the GM1 glycan headgroup and the presence of a lipid tail. Other gangliosides shared similar anti-inflammatory effects in in vitro models, including GD3, GD1a, GD1b, and GT1b. Conversely, GM3 and GQ1b displayed pro-inflammatory activity. The anti-inflammatory effects of GM1 and other gangliosides were partially reproduced by increasing endogenous ganglioside levels with L-t-PDMP, whereas inhibition of glycolipid biosynthesis exacerbated microglial activation in response to LPS stimulation. CONCLUSIONS: Our data suggest that gangliosides are important modulators of microglia inflammatory responses and reveal that administration of GM1 and other complex gangliosides exerts anti-inflammatory effects on microglia that could be exploited therapeutically.

Gangliosides in the Brain: Physiology, Pathophysiology and Therapeutic Applications.

Gangliosides are glycosphingolipids highly abundant in the nervous system, and carry most of the sialic acid residues in the brain. Gangliosides are enriched in cell membrane microdomains ("lipid rafts") and play important roles in the modulation of membrane proteins and ion channels, in cell signaling and in the communication among cells. The importance of gangliosides in the brain is highlighted by the fact that loss of function mutations in ganglioside biosynthetic enzymes result in severe neurodegenerative disorders, often characterized by very early or childhood onset. In addition, changes in the ganglioside profile (i.e., in the relative abundance of specific gangliosides) were reported in healthy aging and in common neurological conditions, including Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), stroke, multiple sclerosis and epilepsy. At least in HD, PD and in some forms of epilepsy, experimental evidence strongly suggests a potential role of gangliosides in disease pathogenesis and potential treatment. In this review, we will summarize ganglioside functions that are crucial to maintain brain health, we will review changes in ganglioside levels that occur in major neurological conditions and we will discuss their contribution to cellular dysfunctions and disease pathogenesis. Finally, we will review evidence of the beneficial roles exerted by gangliosides, GM1 in particular, in disease models and in clinical trials.

Fall incidence and associated risk factors among people with a lower limb amputation during various stages of recovery - a systematic review.

Purpose: The objective of this study was to estimate fall incidence and describe associated risk factors among people with a lower limb amputation (LLA) during various stages of recovery: the surgical ward, in-patient rehabilitation and return to community life. Materials and methods: A systematic search of relevant English language articles was performed using PubMed and EMBASE. Out of 310 initial "hits," six retrospective cohort studies, one prospective cohort study and eleven cross-sectional studies from which fall incidence and risk factors could be extracted, were selected for critical review. Fall incidence and associated risk factors were extracted and analyzed in the context of various clinical stages of recovery after amputation. The studies were evaluated for quality using the "Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies." Results: Results showed that during all stages of recovery, people with a LLA are at increased risk of falling compared with able-bodied individuals, as well as other clinical populations. Each stage of recovery is associated with different fall risk factors. The current review is limited mainly by the paucity of studies on the topic. Conclusions: Specialised care focusing on the most relevant risk factors for each stage of recovery may enhance fall prevention during post-fall recovery. Implications for rehabilitation •  People with a lower limb amputation are at a high risk of falling in all stages of their clinical course.     •  Health professionals should be aware that people with a lower limb amputation in the first 4 years ofamputation or with four or more health-related problems are at an increased risk.   â€¢  Health professionals should also be aware that increased gait variability, excess confidence in balance andwalking abilities and less cautious stair walking, impose an elevated risk of falling and should focus theirefforts in reducing these factors.

The receptor tyrosine kinase TrkB signals without dimerization at the plasma membrane.

Tropomyosin-related tyrosine kinase B (TrkB) is the receptor for brain-derived neurotrophic factor (BDNF) and provides critical signaling that supports the development and function of the mammalian nervous system. Like other receptor tyrosine kinases (RTKs), TrkB is thought to signal as a dimer. Using cell imaging and biochemical assays, we found that TrkB acted as a monomeric receptor at the plasma membrane regardless of its binding to BDNF and initial activation. Dimerization occurred only after the internalization and accumulation of TrkB monomers within BDNF-containing endosomes. We further showed that dynamin-mediated endocytosis of TrkB-BDNF was required for the effective activation of the kinase AKT but not of the kinase ERK1/2. Thus, we report a previously uncharacterized mode of monomeric signaling for an RTK and a specific role for the endosome in TrkB homodimerization.