Interleukin 15 modulates the effects of poly I:C maternal immune activation on offspring behaviour

Maternal infections during pregnancy are linked with an increased risk for disorders like Autism Spectrum Disorder and schizophrenia in the offspring. Although precise mechanisms are still unclear, clinical and preclinical evidence suggest a strong role for maternal immune activation (MIA) in the neurodevelopmental disruptions caused by maternal infection. Previously, studies using the Polyinosinic:Polycytidylic (Poly I:C) MIA preclinical model showed that cytokines like Interleukin 6 (Il6) are important mediators of MIA\u27s effects. In this study, we hypothesized that Il15 may similarly act as a mediator of Poly I:C MIA, given its role in the antiviral immune response. To test this hypothesis, we induced Poly I:C MIA at gestational day 9.5 in wildtype (WT) and Il15−/− rat dams and tested their offspring in adolescence and adulthood. Poly I:C MIA and Il15 knockout produced both independent and synergistic effects on offspring behaviour. Poly I:C MIA decreased startle reactivity in adult WT offspring but resulted in increased adolescent anxiety and decreased adult locomotor activity in Il15−/− offspring. In addition, Poly I:C MIA led to genotype-independent effects on locomotor activity and prepulse inhibition. Finally, we showed that Il15−/− offspring exhibit distinct phenotypes that were unrelated to Poly I:C MIA including altered startle reactivity, locomotion and signal transduction in the auditory brainstem. Overall, our findings indicate that the lack of Il15 can leave offspring either more or less susceptible to Poly I:C MIA, depending on the phenotype in question. Future studies should examine the contribution of fetal versus maternal Il15 in MIA to determine the precise developmental mechanisms underlying these changes

Cognitive, neurophysiological, and molecular alterations following noise-induced hearing loss

Hearing loss is one of the most prevalent, chronic health conditions worldwide, with excessive exposure to loud noise as a leading cause. Beyond the devastating impact of hearing impairment itself, hearing loss has been associated with age-related cognitive impairment. Furthermore, it is well known that noise-induced hearing loss can lead to widespread plasticity in the central auditory pathway, and emerging evidence suggests that brain regions involved in higher-level cognitive functioning, such as the prefrontal cortex and hippocampus, are also affected. Thus, this thesis aims to investigate the cognitive, neurophysiological, and molecular alterations following noise-induced hearing loss using a rat model. Previously, we showed that the prefrontal cortex demonstrates noise-induced plasticity that is not present in the auditory cortex. Thus, in Chapter 2, we determined that impaired gamma phase coherence in the prefrontal cortex was associated with dendritic reorganization and decreased expression of proteins involved in GABAergic and glutamatergic neurotransmission in the prefrontal cortex; findings that were not observed in the auditory cortex, where gamma phase coherence remained unchanged post-noise exposure. In Chapter 3, to elucidate the link between hearing loss and age-related cognitive impairment, we investigated the effect of early-life noise exposure across aging. Our results indicated that not all brain regions appear equally susceptible to noise-induced hearing loss across aging, as noise exposure caused an age-specific deficit in hippocampal-dependent, but not striatal-dependent cognitive function. Furthermore, a subset of younger animals showed noise-induced deficits in spatial learning, suggesting that vulnerable subjects may be more susceptible to the effects of noise exposure. Given this finding, and emerging evidence that hearing loss represents a modifiable risk factor for dementia, we investigated if noise-induced hearing loss could exacerbate Alzheimer’s disease-related neuropathology and cognitive impairment in Chapter 4. Using a genetically susceptible model of Alzheimer’s disease, we observed that noise exposure caused changes that were dependent on genotype, sex, and cognitive domain, indicating a complex relationship between hearing loss and its effects on vulnerable subjects. Overall, this thesis identified novel findings related to the impact of noise-induced hearing loss on neurophysiological and molecular alterations in brain regions subserving cognitive function

Chronic pain management and the development of opioid use disorder: Improving opioid stewardship among Canadian prescribers

Chronic pain is a common condition that impacts quality of life and often precipitates the need for medical attention. Despite evidence that long-term opioid use provides limited relief, prescription opioid therapy remains a cornerstone in the medical management of chronic non-cancer pain. Presently, 13% of Canadians are prescribed opioids for pain management, and physicians play a crucial role in preventing the development of opioid use disorders. However, Canadian physicians lack knowledge of and comfort with evidence-based principles of opioid stewardship. In this article, we aim to highlight ongoing Canadian efforts to address physician discomfort and improve clinical practice. We focus on 2017 Canadian guidelines that provide clinicians with evidence-based recommendations for opioid use in chronic non-cancer pain management. In addition, we call attention to provincial efforts to implement physician accountability measures. In reviewing the existing literature, we uncovered inadequacies in pain management curricula within the Canadian undergraduate and continuing medical education (CME) systems. We consulted the educational practices of the European Pain Federation and the Centers for Disease Control and Prevention to make recommendations for improvement to current Canadian pain curricula. Based on our findings, we recommend that (1) Canadian medical institutions expand upon current core pain curricula, (2) pain management education be made compulsory, (3) academic detailing be emphasized as a means of CME, and (4) multidisciplinary non-medical management of chronic pain be featured more extensively

Big data in healthcare research - how can we address public concerns of privacy

Big data is an emerging technological field that encompasses massive datasets. Its role in the healthcare field is currently being explored and has the potential to greatly improve healthcare and disease surveillance through pattern analysis of health data. Concerns had by the general public focus primarily on potential breaches of privacy and confidentiality of patient medical health records in the context of research. These concerns relate to the innate characteristics of big data, such as large size and fast data acquisition speed, which increases the risk of breaching confidentiality. Therefore, it is important for physicians to be mindful of privacy concerns and maintain trust as big data becomes more prominent. Doing so is a key factor in building public trust in the use. Understanding strategies and limitations of current practice standards will allow physicians to build on existing guidelines to incorporate the rise of big data. This means prioritizing privacy when handling big data through anonymization, creating safe havens and promoting dynamic informed consent practice standards

Maternal Immune Activation by Poly I:C as a preclinical Model for Neurodevelopmental Disorders: A focus on Autism and Schizophrenia

Maternal immune activation (MIA) in response to a viral infection during early and mid-gestation has been linked through various epidemiological studies to a higher risk for the child to develop autism or schizophrenia-related symptoms. This has led to the establishment of the pathogen-free poly I:C-induced MIA animal model for neurodevelopmental disorders, which shows relatively high construct and face validity. Depending on the experimental variables, particularly the timing of poly I:C administration, different behavioural and molecular phenotypes have been described that relate to specific symptoms of neurodevelopmental disorders such as autism spectrum disorder and/or schizophrenia. We here review and summarize epidemiological evidence for the effects of maternal infection and immune activation, as well as major findings in different poly I:C MIA models with a focus on poly I:C exposure timing, behavioural and molecular changes in the offspring, and characteristics of the model that relate it to autism spectrum disorder and schizophrenia

Interactions between lemongrass and lavender essential oils in combination with ampicillin influencing antibacterial activity on Sporosarcina ureae and Serratia liquefaciens

The purpose of this study is to determine the effects of various combinations of essential oils (EOs) with antibiotics on bacterial growth. The molecular mechanisms behind the effects of individual phytochemicals in EOs and antibiotics is well understood, unlike the mechanisms behind the interactions between multiple phytochemicals and antibiotics in a mixture. Serratia liquefaciens and Sporosarcina ureae were exposed to various treatments of different combinations of Lavandula officinalis (lavender oil), Cymbopogon citratus (lemongrass oil) with ampicillin. For each treatment group, mean zones of inhibition (ZOI) were measured after exposure for 48 hours. Controls for both species did not yield any ZOI whereas all other treatments resulted in the inhibition of bacterial growth in both Serratia liquefaciens and Sporosarcina ureae. Statistical analyses showed that the combination of lemongrass oil and ampicillin was significantly more effective than all other treatments for Serratia liquefaciens. The lemongrass oil and ampicillin treatment was the only treatment that displayed additive effects. All treatments for Sporosarcina ureae, with the exception of the control and lavender oil treatments, showed a significantly higher mean ZOI when compared to control and lavender oil treatments. It was concluded that lemongrass oil was a better candidate to be included in antibacterial cocktails than lavender oil. However, further investigation is required to elucidate EOs that interact synergistically with ampicillin when acting on Serratia liquefaciens and Sporosarcina ureae. Additionally, further investigation into the molecular mechanisms behind the interactions of the components found in these EOs with ampicillin is required

Fall 2023: Clinician Investigator Trainee Association of Canada (CITAC)

This has been a great first half of the year for CITAC-ACCFC (Clinician Investigator Trainee Association of Canada/Association des cliniciens-chercheurs en formation du Canada)! We are looking forward to our new members joining us in the fall and welcoming back our previous members after the summer

Overview of The the Clinician Investigator Trainees’ Research Presented at The 2022 CSCI-CITAC Joint Meeting

The 2022 Annual Joint Meeting (AJM) and Young Investigators’ Forum of the Canadian Society for Clinical Investigation / Société Canadienne de recherches clinique (CSCI/SCRC) and Clinician Investigator Trainee Association of Canada/Association des cliniciens-chercheurs en formation du Canada (CITAC/ACCFC) was held in Montréal, November 13–14, 2022. The theme of this year’s AJM was “Strength in Perseverance” and focused on highlighting clinician-investigator trainee achievements and resilience in research engagement through recent challenging and unprecedented times. The opening remarks were given by Nicola Jones (president of CSCI/SCRC) and Heather Whittaker (past president of CITAC/ACCFC). The keynote speaker was Dr. Michael Strong, who delivered the presentation “The Future of Clinician Scientists in Canada.” Dr. Caroline Quach (Université de Montréal) received the CSCI Distinguished Scientist Award and Dr. Amy Metcalfe (University of Calgary) received the CSCI Joe Doupe Young Investigator Award. Each of the clinician-scientists delivered presentations on their award-winning research. The four interactive workshops included “Social Media in Science and Medicine,” “Diversity in Science and Medicine,” “Running a Successful Research Program,” and “Mentorship in Action.” The AJM also included presentations from clinician investigator trainees from across the country. Over 90 abstracts were showcased at this year’s meeting, most of which are summarized in this review. Six outstanding abstracts were selected for oral presentations during the President’s Forum