Medicine and Health Sciences Commons^™

A Review Of The Neural Basis Underlying The Acoustic Startle Response With A Focus On Recent Developments In Mammals, Alice Zheng, Susanne Schmid

Anatomy and Cell Biology Publications

The startle response consists of whole-body muscle contractions, eye-blink, accelerated heart rate, and freezing in response to a strong, sudden stimulus. It is evolutionarily preserved and can be observed in any animal that can perceive sensory signals, indicating the important protective function of startle. Startle response measurements and its alterations have become a valuable tool for exploring sensorimotor processes and sensory gating, especially in the context of pathologies of psychiatric disorders. The last reviews on the neural substrates underlying acoustic startle were published around 20 years ago. Advancements in methods and techniques have since allowed new insights into acoustic startle …

Spatiotemporally Dynamic Electric Fields For Brain Cancer Treatment: An In Vitro Investigation, Erin Iredale, Abdulla Elsaleh, Hu Xu, Paul Christiaans, Andrew Deweyert, John Ronald, Susanne Schmid, Matthew O Hebb, Terry M Peters, Eugene Wong

Anatomy and Cell Biology Publications

Objective. The treatment of glioblastoma (GBM) using low intensity electric fields (∼1 V cm^-1) is being investigated using multiple implanted bioelectrodes, which was termed intratumoral modulation therapy (IMT). Previous IMT studies theoretically optimized treatment parameters to maximize coverage with rotating fields, which required experimental investigation. In this study, we employed computer simulations to generate spatiotemporally dynamic electric fields, designed and purpose-built an IMT device for in vitro experiments, and evaluated the human GBM cellular responses to these fields. Approach. After measuring the electrical conductivity of the in vitro culturing medium, we designed experiments to evaluate the …

Developmental Changes In Electrophysiological Properties Of Auditory Cortical Neurons In The Cntnap2 Knockout Rat, Rajkamalpreet S Mann, Brian L Allman, Susanne Schmid

Anatomy and Cell Biology Publications

Disruptions in the CNTNAP2 gene are known to cause language impairments and symptoms associated with autism spectrum disorder (ASD). Importantly, knocking out this gene in rodents results in ASD-like symptoms that include auditory processing deficits. This study used in vitro patch-clamp electrophysiology to examine developmental alterations in auditory cortex pyramidal neurons of Cntnap2^-/- rats, hypothesizing that CNTNAP2 is essential for maintaining intrinsic neuronal properties and synaptic wiring in the developing auditory cortex. Whole cell patch-clamp recordings were conducted in wildtype and Cntnap2^-/- littermates at three postnatal age ranges (P8-12, P18-21, and …

Differences In Startle And Prepulse Inhibition In Contactin-Associated Protein-Like 2 Knock-Out Rats Are Associated With Sex-Specific Alterations In Brainstem Neural Activity, Alice Zheng, Kaela E Scott, Ashley L Schormans, Rajkamalpreet Mann, Brian L Allman, Susanne Schmid

Anatomy and Cell Biology Publications

The contactin-associated protein-like 2 (CNTNAP2) gene encodes for the CASPR2 protein, which plays an essential role in neurodevelopment. Mutations in CNTNAP2 are associated with neurodevelopmental disorders, including autism spectrum disorder and schizophrenia. Rats with a loss of function mutation in the Cntnap2 gene show increased acoustic startle response (ASR) and decreased prepulse inhibition (PPI). The neural basis of this altered auditory processing in Cntnap2 knock-out rats is currently unknown. Auditory brainstem recordings previously revealed no differences between the genotypes. The next step is to investigate brainstem structures outside of the primary auditory pathway that mediate ASR and PPI, which are …

Characterizing Maternal Isolation-Induced Ultrasonic Vocalizations In A Gene-Environment Interaction Rat Model For Autism., Dorit Möhrle, Megan Yuen, Alice Zheng, Faraj L Haddad, Brian L Allman, Susanne Schmid

Anatomy and Cell Biology Publications

Deficits in social communication and language development belong to the earliest diagnostic criteria of autism spectrum disorders. Of the many risk factors for autism spectrum disorder, the contactin-associated protein-like 2 gene, CNTNAP2, is thought to be important for language development. The present study used a rat model to investigate the potential compounding effects of autism spectrum disorder risk gene mutation and environmental challenges, including breeding conditions or maternal immune activation during pregnancy, on early vocal communication in the offspring. Maternal isolation-induced ultrasonic vocalizations from Cntnap2 wildtype and knockout rats at selected postnatal days were analyzed for their acoustic, temporal and …

Investigating Behavioral Phenotypes Related To Autism Spectrum Disorder In A Gene-Environment Interaction Model Of Cntnap2 Deficiency And Poly I:C Maternal Immune Activation, Faraj L Haddad, Cleusa De Oliveira, Susanne Schmid

Anatomy and Cell Biology Publications

Introduction: Autism Spectrum Disorder (ASD) has been associated with a wide variety of genetic and environmental risk factors in both human and preclinical studies. Together, findings support a gene-environment interaction hypothesis whereby different risk factors independently and synergistically impair neurodevelopment and lead to the core symptoms of ASD. To date, this hypothesis has not been commonly investigated in preclinical ASD models. Mutations in the Contactin-associated protein-like 2 (Cntnap2) gene and exposure to maternal immune activation (MIA) during pregnancy have both been linked to ASD in humans, and preclinical rodent models have shown that both MIA and Cntnap2 deficiency …

Hyperexcitable And Immature-Like Neuronal Activity In The Auditory Cortex Of Adult Rats Lacking The Language-Linked Cntnap2 Gene., Kaela E Scott, Rajkamalpreet S Mann, Ashley L Schormans, Susanne Schmid, Brian L Allman

Anatomy and Cell Biology Publications

The contactin-associated protein-like 2 gene, CNTNAP2, is a highly penetrant risk gene thought to play a role in the genetic etiology of language-related disorders, such as autism spectrum disorder and developmental language disorder. Despite its candidacy for influencing language development, few preclinical studies have examined the role of CNTNAP2 in auditory processing. Using in vivo and in vitro electrophysiological recordings in a rat model with translational validity, we report that a loss of the Cntnap2 gene function caused immature-like cortical evoked potentials, delayed multiunit response latencies to acoustic stimuli, impaired temporal processing, and led to a pattern of hyperexcitability in …

Radiation Exposure Determination In A Secure, Cloud-Based Online Environment, Ben C. Shirley, Eliseos J. Mucaki, Peter Rogan

Biochemistry Publications

Rapid sample processing and interpretation of estimated exposures will be critical for triaging exposed individuals after a major radiation incident. The dicentric chromosome (DC) assay assesses absorbed radiation using metaphase cells from blood. The Automated Dicentric Chromosome Identifier and Dose Estimator System (ADCI) identifies DCs and determines radiation doses. This study aimed to broaden accessibility and speed of this system, while protecting data and software integrity. ADCI Online is a secure web-streaming platform accessible worldwide from local servers. Cloud-based systems containing data and software are separated until they are linked for radiation exposure estimation. Dose estimates are identical to ADCI …

Planning System For The Optimization Of Electric Field Delivery Using Implanted Electrodes For Brain Tumor Control, Erin Iredale, Brynn Voigt, Adam Rankin, Kyungho W Kim, Jeff Z Chen, Susanne Schmid, Matthew O Hebb, Terry M Peters, Eugene Wong

Anatomy and Cell Biology Publications

BACKGROUND: The use of non-ionizing electric fields from low-intensity voltage sources (< 10 V) to control malignant tumor growth is showing increasing potential as a cancer treatment modality. A method of applying these low-intensity electric fields using multiple implanted electrodes within or adjacent to tumor volumes has been termed as intratumoral modulation therapy (IMT).

PURPOSE: This study explores advancements in the previously established IMT optimization algorithm, and the development of a custom treatment planning system for patient-specific IMT. The practicality of the treatment planning system is demonstrated by implementing the full optimization pipeline on a brain phantom with robotic electrode implantation, postoperative imaging, and treatment stimulation.

METHODS: The integrated planning pipeline in 3D Slicer begins with importing and segmenting patient magnetic resonance images (MRI) or computed tomography (CT) images. The segmentation process is manual, followed by a semi-automatic smoothing step that allows …

Improving Accessibility Of Cancer Research (Canadian Cancer Society - Research Information Outreach Team), Harjot Athwal, Alexander Dimitrov, Ava Kavianpour, Urvi Patel

Biochemistry 4455F/G: Translation in Cancer Biology

Cancer is one of the largest human health problems faced globally. Therefore, it is an important focus of research for many disciplines. Cancer research has made significant advancements as clinicians and researchers have expanded their knowledge to better understand this complex disease. Throughout this semester we completed a community engagement learning (CEL) project with the Research Information Outreach Team (RIOT) team from the Canadian Cancer Society (CCS) to promote cancer research amongst adolescents and the general public. We completed blog posts for their website, along with promotional material for their Let’s Talk Cancer (LTC) event and infographics for their social …

Radiation Exposure Determination In A Secure, Cloudbased Online Environment, Ben C. Shirley, Eliseos J. Mucaki, Joan H.M. Knoll, Peter Rogan

Biochemistry Publications

Rapid sample processing and interpretation of estimated exposures will be critical for triaging exposed individuals after a major radiation incident. The dicentric chromosome (DC) assay assesses absorbed radiation using metaphase cells from blood. The Automated Dicentric Chromosome Identifier and Dose Estimator System (ADCI) identifies DCs and determines radiation doses. This study aimed to broaden accessibility and speed of this system, while protecting data and software integrity. ADCI Online is a secure web-streaming platform accessible worldwide from local servers. Cloud-based systems containing data and software are separated until they are linked for radiation exposure estimation. Dose estimates are identical to ADCI …

Differential Behaviour Of Distinct Motoneuron Pools That Innervate The Triceps Surae, Josh W. Cohen, Taian M. Vieira, Tanya D. Ivanova, Jayne Garland

Kinesiology Publications

It has been shown that when humans lean in various directions, the central nervous system (CNS) recruits different motoneuron pools for task completion; common units that are active during different leaning directions, and unique units that are active in only one leaning direction. We used high-density surface electromyography (HD-sEMG) to examine if motor unit (MU) firing behaviour was dependent on leaning direction, muscle (medial and lateral gastrocnemius; soleus), limits of stability, or whether a MU is considered common or unique. Fourteen healthy participants stood on a force platform and maintained their center of pressure in five different leaning directions. HD-sEMG …

Likely Community Transmission Of Covid-19 Infections Between Neighboring, Persistent Hotspots In Ontario, Canada, Ben C. Shirley, Eliseos J. Mucaki, Peter Rogan

Biochemistry Publications

Introduction: This study aimed to produce community-level geo-spatial mapping of confirmed COVID-19 cases in Ontario Canada in near real-time to support decision-making. This was accomplished by area-to-area geostatistical analysis, space-time integration, and spatial interpolation of COVID-19 positive individuals.
Methods: COVID-19 cases and locations were curated for geostatistical analyses from March 2020 through June 2021, corresponding to the first, second, and third waves of infections. Daily cases were aggregated according to designated forward sortation area (FSA), and postal codes (PC) in municipal regions Hamilton, Kitchener/Waterloo, London, Ottawa, Toronto, and Windsor/Essex county. Hotspots were identified with area-to-area tests including Getis-Ord Gi*, Global …

Restructuring Training (Participation House Support Services), Victoria Lun, Do Yeon Oh, Nadir Saeed, Joe Thorne, Alexander Trusler

Medical Sciences 4300A: Addressing Healthcare Misconceptions Using Scientific Inquiry

Participation House Support Services (PHSS) is a non-profit organization with over 60 locations across Ontario that serves individuals with complex medical, physical, and developmental needs with the goal of including them in the community. The scope of the project covers members of the PHSS organization and the London community that they serve by addressing problems with burnout and culture of resentment that the Coordinators of the organization face. After initial discussions with the community partner, qualitative research was done via focus groups with PHSS Coordinators and training staff. An agreed-upon solution of restructuring the training process was developed, as training …

Increasing Civic Engagement And Awareness Of Poverty & Homelessness Through Social Media (Project Hope London), Vanessa Chan, Sairam Gajavelli, Majid Khan, Iris Kwon, Masum Patel

Medical Sciences 4300A: Addressing Healthcare Misconceptions Using Scientific Inquiry

As the Project Hope London (PHL) Social Media Team, the purpose of our project was to utilize social media to support PHL in their goal of helping to improve the overall health of individuals experiencing homelessness. We aimed to broaden the organization’s audience through Instagram as this popular platform has the potential to reach younger demographics, such as the Western student body, and local businesses. Our team took control of their Instagram page to revitalize their social media presence. We redesigned the bio, curated posts with modern aesthetics, and ran a social media campaign to further boost engagement with the …

A Wicked Problem: The Implementation Of Clinical Guidelines Application To Optimize Patient Care (Uhn Openlab), Ardavan Bonyadi Behrouz, Nelson Chang, Jasmine Luo, Daniel Olteanu, Naomi Smith

Medical Sciences 4300A: Addressing Healthcare Misconceptions Using Scientific Inquiry

The purpose of our partnership with the UHN OpenLab was to discover the barriers involved with automating the sporadic release of clinical practice guidelines (CPGs) into the Innovate Guidelines Application (IGA). The problem is considered wicked—interlocking challenges cannot be addressed by a single solution. Accordingly, the goal was to explore the barriers of stakeholders and specialization groups, general guideline issues, and the considerations of healthcare professionals and public perception. An initial literature review was conducted to discover unidentified problems before a first draft of the systems map was created. Subsequently, connections were formed across problems and each was categorized based …

A Physician’S Guide To Clinical Documentation Improvement: Aligning Cdi To Health Information Practice (Canadian Health Information Management Association), Noor Baldawi, Jacky Cheung, Georgia Diamanakis, Alvina Jiwani, Zexi Wang

Medical Sciences 4300A: Addressing Healthcare Misconceptions Using Scientific Inquiry

The field of clinical documentation improvement (CDI) is emerging alongside the need for more accurate health care information that is reflective of the health status of Canadians. Health information management professionals and physicians play a critical role in the collection, transformation, protection, and distribution of clinical documentation. The quality of health data is dependent on the physician’s specificity in clinical documentation of patient health records, as this information is converted into data by coding specialists. Coded medical information, and associated hospital data, provides information surrounding patient severity of disease, a hospital’s expected length of stay, and a hospital’s mortality rate. …

Discovering Body Positivity & Self-Image (Gender Equality Coalition Of Ontario), Ella Clarke, Morolayo Ilori, Melanie Peck, Hannah Polley, Mili Shah

Medical Sciences 4300A: Addressing Healthcare Misconceptions Using Scientific Inquiry

Body image refers to the way we perceive our bodies, and it can positively or negatively impact physical and mental health (Alleva et al., 2015). Unfortunately, negative body image is becoming more common with some studies finding that 65% of young people are dissatisfied with their bodies (Linardon et al., 2021). This can lead to a variety of psychological and behavioral problems and disorders such as body dysmorphia or eating disorders (Alleva et al., 2015). However, many of these consequences associated with negative body image can be circumvented by learning to foster positive body images through building self-esteem (Jessie’s Legacy, …

Addressing Workplace Mental Health During Covid-19 (Global Minds Collective), Candace Brooks-Dasilva, Ashlee Jiang, Priya Modi, Komal Patel, Lilian Raphael

Medical Sciences 4300A: Addressing Healthcare Misconceptions Using Scientific Inquiry

We aimed to produce novel, comprehensive tools to support The Global MINDS Collective’s mission of co-creating unique workplace infrastructures conducive to employee mental wellness. Our Systems Map uses a multifactorial and intersectional approach to analyze how the COVID-19 pandemic has changed employees’ mental and psychosocial wellness. A systems thinking approach was used to connect ideas from literature and industry resources to expand on concepts such as workplace diversity, burnout, and current practices. The interconnected nature of the systems map allowed us to identify “leverage points,” which were topics with a high degree of connectivity that could be targeted for high-impact …

Supporting Pregnant Persons: The Benefits Of Opening A Birth Centre In London, Ontario (Dynamic Doulas Of London), Alisha George, Megan Harris, Allison Kirkpatrick, Lianna Mathew, Amel Sassi

Medical Sciences 4300A: Addressing Healthcare Misconceptions Using Scientific Inquiry

No abstract provided.

Determining The Impacts Of The Sunshine Foundation's Dream-Like Experiences For Children With Severe Physical Disabilities, Jason Chan, Hannah Sendzik, Reya Siby, Sneh Sunder, Matthieu Trudell

Medical Sciences 4300A: Addressing Healthcare Misconceptions Using Scientific Inquiry

The Sunshine Foundation is a charity dedicated to providing dream-like experiences to children and families with severe physical disabilities with the hopes to foster optimism, independence and hope, and improve mental health. However, they lack empirical evidence to illustrate the positive long-term impacts that their wishes provide. Thus, our main goal was to generate quantifiable data to highlight the positive impacts of the program, in order to improve donor interest, raise awareness, and ultimately be able to reach more children nation-wide. We intended to do this through a literature review and present concrete statistical findings through a multi-media deliverable in …

Alignment Of The United Nations Sustainable Development Goals And The London Plan (Citystudio London), Jack Adams, Trent Arnold, Rachel Jairam, Amani Khan

Medical Sciences 4300A: Addressing Healthcare Misconceptions Using Scientific Inquiry

The goal of our project was to map the City of London Plan to the UN’s Sustainability and Development Goals. An aim of the project was to present the contents in the City of London Plan in a more understandable and accessible way for London citizens and city counsellors to be able to engage with. Another aim was to measure the similarities and discrepancies of the London Plan and the UNs SDGs in a quantifiable way that could be easily examined by the city when creating future city plans. Our deliverables were a 1-minute video pitch, an excel spreadsheet that …

Improving Senior Fitness Programs & Dementia Care (Canadian Centre For Activity & Aging), Nidaal Abid, Tarannum Khan, Serena Lai, Kyle Lam, Madeline Macrae, Karen Wong

Medical Sciences 4300A: Addressing Healthcare Misconceptions Using Scientific Inquiry

Our team worked alongside the Canadian Centre for Activity and Aging (CCAA) to improve senior fitness programs and dementia care through volunteering at weekly exercise classes, assisting with fitness assessments, and creating two tangible deliverables. Our first deliverable was a Wordle; a tool for visualizing the modifiable risk factors of dementia. By consulting existing literature, we concluded that hearing loss, low education status, depression, and smoking were the main modifiable risk factors. This Wordle will be used for future research and educational purposes. Our next deliverables targeted the fitness aspect of the CCAA. We helped facilitate weekly instructor-led fitness classes …

A Complete Guide To Incorporation (Project Hope London), Kevin Dong, Karen Guirguis, Rozmin Jasani, Samuel Luo, Sahara Rosha

Medical Sciences 4300A: Addressing Healthcare Misconceptions Using Scientific Inquiry

Our team worked with Project Hope (PH)–a grassroots organization that supports London’s population experiencing homelessness via needs-based outreach, community building, and housing support. PH serves 250 individuals/week at outreach and intends to expand this number and explore larger-scale projects such as affordable housing initiatives. However, to attain these goals, PH needs more funding–which it has struggled to obtain due to its lack of Registered Charity (RC) status. RCs are the only not-for-profit organizations that can issue tax receipts to monetary donors, and several commercial donors only donate to RCs for this reason. Thus, our deliverable intends to streamline PH’s progress …

Stakeholders Surrounding Assisted & Affordable Housing (The Unity Project), Jiyoon Choi, Mahir Rahman, Adesh Suchit, Kenneth Wong

Medical Sciences 4300A: Addressing Healthcare Misconceptions Using Scientific Inquiry

Our team worked with the Unity Project, a registered charity in London that provides emergency shelter and supportive housing, to address the current needs of the organization based on a research and evidence-based approach. Specifically, we aimed to support their goals relating to the need for improved affordable housing solutions in London and the current divide between the different stakeholders involved. We provided two main deliverables: a) a report and slide deck that outline the positions of key stakeholders involved with affordable housing, and b) a set of three infographics that provide information that connects the homeless community to useful …

Embracing Culture At The Centre Of Hope Food Bank (Salvation Army), Angela Chen, Ewan Kelly, Caitlin Lee, Sumin Shin

Medical Sciences 4300A: Addressing Healthcare Misconceptions Using Scientific Inquiry

The purpose of our project was to expand the food options provided at the Centre of Hope (COH) to better reflect the cultural diversity that exists within the London community. Overall, our project aimed to provide all individuals with the opportunity to consume food they are familiar and comfortable with, using a food choice-model system. This involved the creation of four deliverables: a comprehensive list of food options specific to the major minority groups in London, a culturally-specific food preference survey (physical and online versions, to improve accessibility), and a flyer with a QR code to encourage survey responses. The …

Improved Radiation Expression Profiling In Blood By Sequential Application Of Sensitive And Specific Gene Signatures, Eliseos J. Mucaki, Ben C. Shirley, Peter K. Rogan

Biochemistry Publications

Purpose. Combinations of expressed genes can discriminate radiation-exposed from normal control blood samples by machine learning based signatures (with 8 to 20% misclassification rates). These signatures can quantify therapeutically-relevant as well as accidental radiation exposures. The prodromal symptoms of Acute Radiation Syndrome (ARS) overlap those present in Influenza and Dengue Fever infections. Surprisingly, these human radiation signatures misclassified gene expression profiles of virally infected samples as false positive exposures. The present study investigates these and other confounders, and then mitigates their impact on signature accuracy.

Methods. This study investigated recall by previous and novel radiation signatures independently derived …

Rapid Microscopic Fractional Anisotropy Imaging Via An Optimized Linear Regression Formulation., N J J Arezza, D H Y Tse, C A Baron

Medical Biophysics Publications

Water diffusion anisotropy in the human brain is affected by disease, trauma, and development. Microscopic fractional anisotropy (μFA) is a diffusion MRI (dMRI) metric that can quantify water diffusion anisotropy independent of neuron fiber orientation dispersion. However, there are several different techniques to estimate μFA and few have demonstrated full brain imaging capabilities within clinically viable scan times and resolutions. Here, we present an optimized spherical tensor encoding (STE) technique to acquire μFA directly from the 2nd order cumulant expansion of the powder averaged dMRI signal obtained from direct linear regression (i.e. diffusion kurtosis) which requires fewer powder-averaged signals than …

Experimental And Computational Observations Of Immunogenic Cobalt Porphyrin Lipid Bilayers: Nanodomain-Enhanced Antigen Association., Jasmin Federizon, Conrard Giresse Tetsassi Feugmo, Wei-Chiao Huang, Xuedan He, Kazutoyo Miura, Aida Razi, Joaquin Ortega, Mikko Karttunen, Jonathan F Lovell

Chemistry Publications

Cobalt porphyrin phospholipid (CoPoP) can incorporate within bilayers to enable non-covalent surface-display of antigens on liposomes by mixing with proteins bearing a polyhistidine tag (his-tag); however, the mechanisms for how this occurs are poorly understood. These were investigated using the his-tagged model antigen Pfs25, a protein antigen candidate for malaria transmission-blocking vaccines. Pfs25 was found to associate with the small molecule aquocobalamin, a form of vitamin B12 and a cobalt-containing corrin macrocycle, but without particle formation, enabling comparative assessment. Relative to CoPoP liposomes, binding and serum stability studies indicated a weaker association of Pfs25 to aquocobalamin or cobalt nitrilotriacetic acid …

Gabab Receptor Agonist R-Baclofen Reverses Altered Auditory Reactivity And Filtering In The Cntnap2 Knock-Out Rat, Dorit Möhrle, Wenxuan Wang, Shawn N Whitehead, Susanne Schmid

Anatomy and Cell Biology Publications

Altered sensory information processing, and auditory processing, in particular, is a common impairment in individuals with autism spectrum disorder (ASD). One prominent hypothesis for the etiology of ASD is an imbalance between neuronal excitation and inhibition. The selective GABA_B receptor agonist R-Baclofen has been shown previously to improve social deficits and repetitive behaviors in several mouse models for neurodevelopmental disorders including ASD, and its formulation Arbaclofen has been shown to ameliorate social avoidance symptoms in some individuals with ASD. The present study investigated whether R-Baclofen can remediate ASD-related altered sensory processing reliant on excitation/inhibition imbalance in the auditory brainstem. …