Table S4. PLSDA analysis of biomarker concentrations in healthy male vs. female athletes. (DOCX 1... more Table S4. PLSDA analysis of biomarker concentrations in healthy male vs. female athletes. (DOCX 16 kb)
Figure S1. PLS correlations between inflammatory profiles and days to blood draw post-injury in a... more Figure S1. PLS correlations between inflammatory profiles and days to blood draw post-injury in athletes with SRC. (DOCX 14 kb)
Table S3. PLSDA analysis of biomarker concentrations in healthy athletes dichotomized into two gr... more Table S3. PLSDA analysis of biomarker concentrations in healthy athletes dichotomized into two groups: ≤ 3 h from their last bout of physical activity vs. > 3 h from their last bout of physical activity. (DOCX 16 kb)
Journal of Military, Veteran and Family Health, 2020
Introduction: Amidst the 2020 COVID-19 pandemic, frontline healthcare workers may be faced with a... more Introduction: Amidst the 2020 COVID-19 pandemic, frontline healthcare workers may be faced with a host of challenging decisions and decisional consequences made within the context of potential shor...
BACKGROUND Military members (MMs), including Canadian Armed Forces (CAF) Service members (SMs), a... more BACKGROUND Military members (MMs), including Canadian Armed Forces (CAF) Service members (SMs), and Veterans are at elevated risk of experiencing occupational traumas which can cause operational stress injuries (OSIs) including post-traumatic stress disorder (PTSD), and moral injury (MI). Traditional evidence-based psychotherapeutic interventions can be effective in reducing symptoms of PTSD. Some MMs and Veterans, however, are less responsive to these treatments and considered to have Treatment-Resistant PTSD (TR-PTSD). Multi-modular Motion-Assisted Memory Desensitization and Reconsolidation (3MDR) is an intervention delivered within a virtual reality (VR) environment that has been introduced to MMs and Veterans who experience PTSD related to military service. Utilizing the Computer-Assisted Rehabilitation Environment (CAREN), 3MDR incorporates exposure therapy, psychotherapy, Eye Movement Desensitization and Reconsolidation (EMDR), VR, supportive counselling, and treadmill walking...
Journal of Military, Veteran and Family Health, 2020
While the basics of pharmacokinetics and pharmacodynamics have not changed much in the past two d... more While the basics of pharmacokinetics and pharmacodynamics have not changed much in the past two decades, the world of pharmacogenomics has seen much advancement and refinement. These advances have improved the clinical utility and applicability for those caring for individuals with a range of conditions. Indeed, there are now simple clinical tests that can tell a provider potentially useful information about clinical decisions regarding prescribing practices. This article reviews the basics of pharmacokinetics and drug interactions before covering the concepts of pharmacogenomics and pharmacogenomics testing. Further, it discusses the topic of pharmacogenomics testing as it relates to the practice of military mental health providers. It explores several case scenarios to aid in clinical relevance and understanding. This article also addresses the issue of baseline pharmacogenomic testing; A recent Canadian military example and an in-depth table of commercially available pharmacogeno...
Physical stress provides an easily manipulated experimental model that allows for the study of in... more Physical stress provides an easily manipulated experimental model that allows for the study of interactions between the neuroendocrine and immune systems. Severe exercise elicits marked alterations in circulating stress hormones, causing shifts in leukocyte mobilization and function both during and after exercise. Circulating levels of glucocorticoids and their receptors are known to be altered by acute and chronic exercise. Cortisol binds to the cytosolic glucocorticoid receptors (GCRs) in leukocytes resulting in GC-mediated immunosuppression. Long-term GCRs dysfunction in leukocytes can enhance susceptibility to autoimmune and inflammatory diseases. This study examined physiological cortisol release with strenuous exercise, and measured GCR translocations in peripheral blood T lymphocytes and total leukocytes before and after intense exercise using multispectral imaging flow cytometry. Blood samples were collected before and after intense exercise from 8 healthy participants. The cytosolic levels of FITC-GCRs, GC-GCR complex nuclear (Vybrant Dye) and mitochondria (MitoTrackerRed) translocations were determined for total leukocytes (Leu) and CD3 + lymphocytes. The image-based measurement showed that there was a biphasic response in GCR translocation to the nucleus on the CD3 + GCR Dim lymphocytes before (88%), immediately after (36%) and 30-min (90%) after exercise. There was no change in the CD3 + GCR Bright lymphocytes. The GCR nuclear translocation on GCR Dim Leu expressed a biphasic trend, pre (74%), immediately post (25%) and 30-min (80%) post exercise. The GCR Bright Leu had shown a decreased in GCR translocation over time. It was observed that a portion of the GCR Dim lymphocytes and GCR Dim Leu translocated to the mitochondria after exercise stress. Our data provide insights into the pathophysiological role and mechanisms of cortisol and GCRs on immune cells under subclinical physical stress. This method is particularly important in understanding the GC-induced apoptosis via mitochondria translocation and GC-mediated immunosuppression through nuclear translocation in inflammatory diseases.
The aim of the study was to evaluate the feasibility of a prehospital trial comparing hypertonic ... more The aim of the study was to evaluate the feasibility of a prehospital trial comparing hypertonic saline and dextran (HSD) with normal saline (NS) in blunt head injury patients. The study used a double blind randomized trial. The study was conducted in air and land emergency medical services and 2 trauma centers serving a population of 4 million people. The study population consisted of head injured, blunt trauma adult patients with a Glasgow Coma Scale of lower than 9. We used 250 mL of HSD vs NS given within 4 hours of the accident. The specific objectives were to assess protocol-related logistical issues, randomization, HSD safety, and follow up rates and to obtain survival and neurocognitive end point estimates. Of 132 eligible patients, 113 were randomized. Nineteen eligible patients were missed because of lack of time (9 [22%]), paramedic discretion (3 [7%]), the paramedic forgot (6 [15%]), and the paramedic refused (1 [2%]). Randomization compliance was 96% (109/113). Four randomized cases met exclusion criteria: penetrating trauma (1), cardiac arrest (2), and fall from standing (1). Three randomized patients were excluded from the final analysis: 2 patients received less than 50 mL of study solution due to an interstitial intravenous line and 1 lost randomization identification. Fifty patients (47%) were randomized to HSD and 56 (53%) to NS. Mean injury severity score was 32.7 for HSD and 32.6 for NS. There was no difference in length of stay, Sequential Organ Failure Assessment maximum, Multiple Organ Dysfunction Score maximum, delta Multiple Organ Dysfunction Score, or Apache scores. Initial head scans scored 3 or higher by Marshall classification for 12 HSD and 11 NS patients. Zero adverse events occurred, and follow-up for the primary outcome was 100%. Alive at 30 days for HSD and NS, respectively, was 70% (35/50) and 75% (42/56) and at discharge was 68% (34/50) and 73% (41/56). Only 49.3% (37/77) of surviving patients consented to follow-up at 4 months and 89% (33/37) completed the assessment. Disability rating scale (median, interquartile range) was 3 (0, 6) for HSD and was 0 (0, 6) for NS. Glasgow Outcome Scale Evaluation was higher than 4 for HSD (12/12 [100%]) and NS (15/21 [72%]). Functional Independence Measure (mean, SD) was 62 (37) for HSD and 80 (32) for NS. It is feasible to conduct a prehospital randomized controlled trial with HSD for treatment of blunt trauma patients with head injuries; however, consent for neurofunctional outcomes in this cohort is problematic and threatens the feasibility of definitive trials using these potentially meaningful end points.
Table S4. PLSDA analysis of biomarker concentrations in healthy male vs. female athletes. (DOCX 1... more Table S4. PLSDA analysis of biomarker concentrations in healthy male vs. female athletes. (DOCX 16 kb)
Figure S1. PLS correlations between inflammatory profiles and days to blood draw post-injury in a... more Figure S1. PLS correlations between inflammatory profiles and days to blood draw post-injury in athletes with SRC. (DOCX 14 kb)
Table S3. PLSDA analysis of biomarker concentrations in healthy athletes dichotomized into two gr... more Table S3. PLSDA analysis of biomarker concentrations in healthy athletes dichotomized into two groups: ≤ 3 h from their last bout of physical activity vs. > 3 h from their last bout of physical activity. (DOCX 16 kb)
Journal of Military, Veteran and Family Health, 2020
Introduction: Amidst the 2020 COVID-19 pandemic, frontline healthcare workers may be faced with a... more Introduction: Amidst the 2020 COVID-19 pandemic, frontline healthcare workers may be faced with a host of challenging decisions and decisional consequences made within the context of potential shor...
BACKGROUND Military members (MMs), including Canadian Armed Forces (CAF) Service members (SMs), a... more BACKGROUND Military members (MMs), including Canadian Armed Forces (CAF) Service members (SMs), and Veterans are at elevated risk of experiencing occupational traumas which can cause operational stress injuries (OSIs) including post-traumatic stress disorder (PTSD), and moral injury (MI). Traditional evidence-based psychotherapeutic interventions can be effective in reducing symptoms of PTSD. Some MMs and Veterans, however, are less responsive to these treatments and considered to have Treatment-Resistant PTSD (TR-PTSD). Multi-modular Motion-Assisted Memory Desensitization and Reconsolidation (3MDR) is an intervention delivered within a virtual reality (VR) environment that has been introduced to MMs and Veterans who experience PTSD related to military service. Utilizing the Computer-Assisted Rehabilitation Environment (CAREN), 3MDR incorporates exposure therapy, psychotherapy, Eye Movement Desensitization and Reconsolidation (EMDR), VR, supportive counselling, and treadmill walking...
Journal of Military, Veteran and Family Health, 2020
While the basics of pharmacokinetics and pharmacodynamics have not changed much in the past two d... more While the basics of pharmacokinetics and pharmacodynamics have not changed much in the past two decades, the world of pharmacogenomics has seen much advancement and refinement. These advances have improved the clinical utility and applicability for those caring for individuals with a range of conditions. Indeed, there are now simple clinical tests that can tell a provider potentially useful information about clinical decisions regarding prescribing practices. This article reviews the basics of pharmacokinetics and drug interactions before covering the concepts of pharmacogenomics and pharmacogenomics testing. Further, it discusses the topic of pharmacogenomics testing as it relates to the practice of military mental health providers. It explores several case scenarios to aid in clinical relevance and understanding. This article also addresses the issue of baseline pharmacogenomic testing; A recent Canadian military example and an in-depth table of commercially available pharmacogeno...
Physical stress provides an easily manipulated experimental model that allows for the study of in... more Physical stress provides an easily manipulated experimental model that allows for the study of interactions between the neuroendocrine and immune systems. Severe exercise elicits marked alterations in circulating stress hormones, causing shifts in leukocyte mobilization and function both during and after exercise. Circulating levels of glucocorticoids and their receptors are known to be altered by acute and chronic exercise. Cortisol binds to the cytosolic glucocorticoid receptors (GCRs) in leukocytes resulting in GC-mediated immunosuppression. Long-term GCRs dysfunction in leukocytes can enhance susceptibility to autoimmune and inflammatory diseases. This study examined physiological cortisol release with strenuous exercise, and measured GCR translocations in peripheral blood T lymphocytes and total leukocytes before and after intense exercise using multispectral imaging flow cytometry. Blood samples were collected before and after intense exercise from 8 healthy participants. The cytosolic levels of FITC-GCRs, GC-GCR complex nuclear (Vybrant Dye) and mitochondria (MitoTrackerRed) translocations were determined for total leukocytes (Leu) and CD3 + lymphocytes. The image-based measurement showed that there was a biphasic response in GCR translocation to the nucleus on the CD3 + GCR Dim lymphocytes before (88%), immediately after (36%) and 30-min (90%) after exercise. There was no change in the CD3 + GCR Bright lymphocytes. The GCR nuclear translocation on GCR Dim Leu expressed a biphasic trend, pre (74%), immediately post (25%) and 30-min (80%) post exercise. The GCR Bright Leu had shown a decreased in GCR translocation over time. It was observed that a portion of the GCR Dim lymphocytes and GCR Dim Leu translocated to the mitochondria after exercise stress. Our data provide insights into the pathophysiological role and mechanisms of cortisol and GCRs on immune cells under subclinical physical stress. This method is particularly important in understanding the GC-induced apoptosis via mitochondria translocation and GC-mediated immunosuppression through nuclear translocation in inflammatory diseases.
The aim of the study was to evaluate the feasibility of a prehospital trial comparing hypertonic ... more The aim of the study was to evaluate the feasibility of a prehospital trial comparing hypertonic saline and dextran (HSD) with normal saline (NS) in blunt head injury patients. The study used a double blind randomized trial. The study was conducted in air and land emergency medical services and 2 trauma centers serving a population of 4 million people. The study population consisted of head injured, blunt trauma adult patients with a Glasgow Coma Scale of lower than 9. We used 250 mL of HSD vs NS given within 4 hours of the accident. The specific objectives were to assess protocol-related logistical issues, randomization, HSD safety, and follow up rates and to obtain survival and neurocognitive end point estimates. Of 132 eligible patients, 113 were randomized. Nineteen eligible patients were missed because of lack of time (9 [22%]), paramedic discretion (3 [7%]), the paramedic forgot (6 [15%]), and the paramedic refused (1 [2%]). Randomization compliance was 96% (109/113). Four randomized cases met exclusion criteria: penetrating trauma (1), cardiac arrest (2), and fall from standing (1). Three randomized patients were excluded from the final analysis: 2 patients received less than 50 mL of study solution due to an interstitial intravenous line and 1 lost randomization identification. Fifty patients (47%) were randomized to HSD and 56 (53%) to NS. Mean injury severity score was 32.7 for HSD and 32.6 for NS. There was no difference in length of stay, Sequential Organ Failure Assessment maximum, Multiple Organ Dysfunction Score maximum, delta Multiple Organ Dysfunction Score, or Apache scores. Initial head scans scored 3 or higher by Marshall classification for 12 HSD and 11 NS patients. Zero adverse events occurred, and follow-up for the primary outcome was 100%. Alive at 30 days for HSD and NS, respectively, was 70% (35/50) and 75% (42/56) and at discharge was 68% (34/50) and 73% (41/56). Only 49.3% (37/77) of surviving patients consented to follow-up at 4 months and 89% (33/37) completed the assessment. Disability rating scale (median, interquartile range) was 3 (0, 6) for HSD and was 0 (0, 6) for NS. Glasgow Outcome Scale Evaluation was higher than 4 for HSD (12/12 [100%]) and NS (15/21 [72%]). Functional Independence Measure (mean, SD) was 62 (37) for HSD and 80 (32) for NS. It is feasible to conduct a prehospital randomized controlled trial with HSD for treatment of blunt trauma patients with head injuries; however, consent for neurofunctional outcomes in this cohort is problematic and threatens the feasibility of definitive trials using these potentially meaningful end points.
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