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3rd Annual Bench to Bedside Translational Medicine Talks

The Bench to Bedside Students' Association hosted our Translational Medicine Talks on November 24th, 2021. These talks serve as a platform for young researchers to give an elevated, innovative and inspiring 8-minute talk with the theme of translational medicine. Watch these research trainees tell a tale about how a treatment or intervention made its way from the bench to the bedside!

Participant Abstracts:

Zoe Hu - Predicting Placental Disease with a Two-Stage Neural Network Pipeline

Diseases related to the placenta, such as preeclampsia and fetal growth restriction, are major causes of mortality and morbidity. As placentally-mediated diseases are often clinically unrecognized until later stages, early diagnosis is required to allow earlier intervention, which is particularly challenging in low-resource areas without subspecialty clinicians. We propose a model utilizing a two-stage convolutional neural network pipeline to classify the presence of placental disease. The pipeline involves a segmentation stage to extract the placenta followed by a classification stage. We evaluated the pipeline on retrospectively collected placenta ultrasounds and diagnostic outcomes of 321 patients taken by 18 sonographers and 3 ultrasound machines. Compared to existing clinical algorithms and neural networks, our classifier achieved significantly higher accuracy of 0.81 ± 0.02 (p < 0.05). This study provides support that automated image analysis of ultrasound texture may assist physicians in early identification of placental disease, with potential benefits to low-resource environments.

Madeleine Wiebe - Getting the full picture: The use of characterizing the immune responses in pregnancy-associated malaria in vivo

Repeated exposure to malaria in childhood can result in protective immunity that reduces

parasite invasion of red blood cells and the sequestration of infected red blood cells (iRBC) in

the tissues. However, pregnancy offers a new site of attack for the parasite, the placenta. Here,

iRBCs bind to chondroitin sulfate A (CSA) and sequester here via variable surface antigens

(VSAs) that are only expressed during pregnancy. One known VSA is VAR2CSA, a large 350

kD protein. Common outcomes of pregnancy-associated malaria (PAM) include low birth

weight, infants that are small for gestational age, and maternal anemia. In high transmission

areas, multiple infections of PAM can result in acquired antibodies that block iRBC binding to

CSA. Thus, these antibodies may be protective against adverse birth outcomes. Cytophilic

antibodies acquired after malaria infection may mediate this protection through various immune

mechanisms. Here, we observed the activation of the classical complement system and opsonic

phagocytosis. We studied a cohort of Colombian pregnant women who developed at least one

submicroscopic infection (SMI) of PAM during pregnancy. Previously, we observed a protective

association between antibody inhibition against iRBC binding to CSA in vitro and levels of

maternal hemoglobin at delivery, but the mechanisms behind this association are unknown. We

continued this investigation by characterizing serological and functional responses in serum

collected from this cohort at study enrollment and delivery. We observed variable levels of IgG

and IgM-VAR2CSA, but these measurements were not associated with pregnancy outcomes. In

the functional assays, both C1q fixation and opsonic phagocytosis was negatively associated

with infant birthweight. This may indicate a dysregulated immune response which could

contribute to placental pathology, but further investigation is required. Additionally, IgM-

VAR2CSA and C1q fixation levels were highly associated to each other in early pregnancy and

at delivery, which suggests IgM may fix C1q to a greater extent than IgG antibodies. The

characterization of immune responses in samples collected from unique cohorts of pregnant

women across the globe is key to understand immunity in the PAM setting and use this

knowledge as guidelines for therapy and vaccine development.

Peter Anto Johnson - An advanced robotic rehabilitation system for mobility training in patients after neurological injury

After a stroke or neurological injury, the upper limb motor and fine-dexterity function can become physiologically compromised. We aimed to evaluate a sensorimotor platform for mobility training. To do this, we calculated optimizations, developed design specifications, and performed MATLAB simulation testing using three-dimensional acceleration dynamics data. We designed a system with a trans-radial segment capacitating motions for multiple degrees of freedom, determining optimal design specifications for the platform. We calculated an overall resolution and sensitivity of 0.08 mg and 256 mV/g for our model, compared to 3 mg and 100 mV/g and 2 mg and 160 mV/g for conventional and standard MEMs accelerometer sensor platforms, respectively. Simulated acceleration dynamics data for movement in six degrees of freedom produced integrated acceleration values over time with a signal-noise reduction. This model offers a proof-of-concept for mobility training in patients with neurological injury; now, our model must be clinically validated.

Sarah Almas - Would You Use an Air Quality Sensor to Control Asthma Attacks?

Asthma is the most common chronic disease of childhood in Canada. Despite advances in therapies, symptomatic control remains an unmet goal. With the current pandemic, household pollutants are expected to increasingly impact asthma control. Measuring indoor air quality holds potential as an efficient strategy for controlling symptoms. However, the acceptability of implementing an indoor sensor has yet to be discovered. Here, we hypothesize that families will be receptive to installing an indoor air quality sensor after understanding its health benefits. We recruited 7 caretakers of children with asthma to complete a questionnaire; here, most respondents (5/7) were likely/very likely to use the sensor out of personal interest, and all respondents would for research purposes. Barriers to use included cost (5/7), intrusiveness and value (3/7). Small size and mobility (5/7) would make it more acceptable. This pilot study is important for asthma control to improve the lives of young asthmatics.

Shubham Soni - Ketone Therapy: Capitalizing on The Body’s Hidden Defence

Ketone bodies are classically known to function as an additional source of fuel in low energy conditions, such as fasting or prolonged exercise. Although important in normal physiology, high ketone levels were historically thought to be detrimental due to conditions such as diabetes. However, recent evidence suggests that elevated ketones this may be an adaptive response such that elevated ketones may be the body’s defense mechanism. Thus, this reveals a novel therapeutic approach. In addition to being a metabolic fuel, ketone bodies also have non-metabolic signalling properties such as reducing inflammation and oxidative stress, both of which are key components of heart failure and cardiovascular disease. Therefore, we may be able to use “ketones therapy” to improve metabolism, inflammation, and oxidative stress in cardiovascular diseases. Using a new and safe method of ketone delivery, we hope that our work may reveal the potential of “ketone therapy” for treating inflammation-mediated diseases.

John Christy Johnson - Mechanical Strain Rehabilitation Device to Bolster Bone Strength in Osteopenia

Disuse osteopenia is a condition that can significantly reduce bone strength and skeletal integrity as a result of prolonged periods of non-weight-bearing. Here, we propose to develop a similar mechanical strain device that can be incorporated into microgravity conditions for astronauts on space missions, who are at 10 times the risk of postmenopausal women for developing osteopenia. We aim to a) describe the pathophysiological mechanism of bone loss; and b) design a mechanical strain device that can be easily embedded into one's long bones. In doing so, we improve health outcomes, maintain peak performance during space missions and partially reduce the cost burden for rehabilitation post-flight. The device can also be repurposed to help postmenopausal women who are at an increased risk of bone fracture and osteopenia.

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