Examination of the Monoamine Oxidase A Gene Promoter on Motivation to Exercise and Levels of Voluntary Physical Activity

Purpose: The purpose of this study was to examine the genetic basis underlying voluntary exercise. Monoamine oxidase A (MAO-A) is an enzyme that acts on monoamine neurotransmitters, such as dopamine, to cause inactivation. There are several polymorphisms in the promoter region of the MAO-A gene, and these variations change transcriptional activity and the amount of MAO-A produced, leading to alterations in available dopamine levels. Interestingly, polymorphisms in MAO-A have been associated recently with physical activity level. This study sought to determine whether there is an association between motivation to exercise, levels of voluntary physical activity, and MAO-A gene polymorphisms. Methods: Seventy-one participants (age 18-24 years, 13 males & 58 females) completed the Behavioral Regulation in Exercise Questionnaire-2 (BREQ-2) to assess their motivation to exercise and the International Physical Activity Questionnaire (IPAQ) to assess their level of physical activity. DNA was collected and isolated from a cheek cell sample. The MAO-A genotype was identified using PCR with gene specific primers. MAO-A 3/3 and 4/4 genotype individuals were used for analysis. Results: External motivation to exercise was significantly higher (p \u3c 0.01) in the high transcription 4/4 genotype (x̄=1.11 ± 0.8) compared to the low transcription 3/3 genotype (x̄= 0.39 ± 0.6). Internal motivation to exercise was not different between genotypes. Body mass index and weekly MET minutes estimated by IPAQ were also comparable between genotypes. Conclusion: The results suggest a polymorphism in this monoamine pathway may play a role in increasing sensitivity to external factors that motivate individuals to exercise

The Effects of Physical Activity on Stress-induced Cardiac Fibrosis

Purpose: This study examined whether routine physical activity limits stress-induced tissue remodeling processes that lead to cardiac fibrosis. The study also explored whether the cardiac urocortin 2/corticotropin releasing factor receptor 2β pathway was activated during physical activity and involved in reducing fibrotic processes. Methods: C67BL/6J male mice were divided into four groups (n=8/group): sedentary/control, voluntary running/control, sedentary/stress and voluntary running/stress. Voluntary running groups were given 24-hour access to a running wheel in the home cage for 9 weeks. During the 9th week, stress groups were exposed to a 5-day resident-intruder stress paradigm that models human post-traumatic stress outcomes. Ventricular cardiac tissue was collected for analysis. Results: Mice ran an average of 4.75 ± 1 km each night. Interestingly, running behavior essentially ceased following stress. Running distance dropped to 0.31 km following the 1st stress day. Some habituation to stress occurred, as running distance increased to 1.12 km by the 5th day of stress but remained significantly lower than pre-stress running distances and distances recorded in non-stressed mice. Quantitative RT-PCR showed small changes in ventricular urocortin 2 and CRF-R2β expression in the running groups. TGF-β, a signaling molecule known to induce fibrosis, had comparable expression levels across groups over controls. Conclusion: Further work is planned to fully characterize urocortin 2/ CRF-R2β and fibrotic processes. Our running data lead us in a new direction, as we have stumbled upon a paradigm that will be useful to study underlying mechanisms by which stress exposure impairs physical activity behavior

Examination of the Monoamine Oxidase a Gene Promoter on Motivation to Exercise and Levels of Voluntary Physical Activity

Purpose: Monoamine oxidase A (MAO-A) is an enzyme that causes inactivation of monoamine neurotransmitters, such as dopamine. Polymorphisms in the promoter region of the MAO-A gene can change transcriptional activity and the amount of MAO-A produced, leading to alterations in available dopamine levels. MAO-A polymorphisms have been associated with physical activity level. This study examined whether motivation to exercise, and levels of voluntary physical activity are associated with MAO-A gene polymorphisms. Methods: Seventy-one participants (18-24 years, 13 males & 58 females) completed the Behavioral Regulation in Exercise Questionaire-2 (BREQ-2) to assess their motivation to exercise and the International Physical Activity Questionnaire (IPAQ) to assess their level of physical activity. DNA was isolated from a cheek cell sample. MAO-A 3/3 and 4/4 genotype individuals were used for analysis. Results: External motivation to exercise was significantly higher (p \u3c 0.01) in the high transcription 4/4 genotype (ave 1.17 ± 0.7) compared to the low transcription 3/3 genotype (ave 0.42 ± 0.5). Internal motivation to exercise, body mass index, and weekly MET minutes were comparable between genotypes. Conclusion: The results suggest a polymorphism in this monoamine pathway may play a role in increasing sensitivity to external factors that motivate individuals to exercise

Cessation of Nightly Voluntary Wheel Running Activity Following Exposure to a Mouse Model of Posttraumatic Stress

Regular physical activity (PA) is well known to positively impact physical and mental health outcomes. In our work to examine cardiovascular benefits of PA in a mouse model of posttraumatic stress, we stumbled upon the reciprocal relationship between PA and stress exposure, wherein stress significantly reduced healthy levels of routine PA. The aim of the present studies was to define the parameters of our paradigm. C67BL/6J male mice were divided into four groups (n=8/group): sedentary/control, voluntary running/control, sedentary/stress, and voluntary running/stress. Voluntary running groups were given unlimited access to a running wheel for 9 weeks. Stress groups were then exposed to a 5-day resident-intruder social stress that models human posttraumatic stress. Running behavior essentially ceased following stress. Habituation to stress occurred, as running distance increased by the 5th day of stress but remained significantly low. A separate study examined a single exposure to resident-intruder social stress. Plasma corticosterone significantly increased while nightly running dropped significantly but returned to normal by the 3rd night post-stress. These studies show the sensitivity of habitual running behavior to stress exposure and suggest the utility of this mouse model in exploring the means by which stress negatively impacts routine PA

The Vehicle, Spring 1999

Vol. 40, No. 2 Table of Contents Poetry Eve\u27s DaughterSylvia Whippopage 1 When We Wore Canoes On Our ShouldersMandy Watsonpage 2 This Is Not A Poem About GrandpaJake Tolbertpage 3 Old relationshipsBrandi Kinneypage 5 UntitledErin Winnerpage 6 BraverySylvia Whippopage 6 deep dark closetNicole Smithpage 7 Belly EarthTara Coburnpage 9 The River and FireJake Tolbertpage 10 UntitledAutumn Williamspage 12 Action PotentialKim Evanspage 13 Chimerical (a song for children)D.M. Attrapepage 14 UntitledAutumn Williamspage 16 UntitledMatthew Armstrongpage 18 Building YouSylvia Whippopage 19 RunningKim Evanspage 20 Walking Jenn to WorkJake Tolbertpage 22 Looking InKim Hunterpage 23 Void Between Me and WisconsinMandy Watsonpage 24 Artwork UntitledWendy Finchpage 4 MeditationJennifer Lundpage 8 UntitledSteve Drakepage 15 MemoriesJennifer Lundpage 21 UntitledKathryn Kolasinskipage 25 Prose FoundKim Hunterpage 26 A Day in the Life of William Baxter, DriverDaniel Fitzgeraldpage 32https://thekeep.eiu.edu/vehicle/1072/thumbnail.jp

The Vehicle, Spring 1999

Vol. 40, No. 2 Table of Contents Poetry Eve\u27s DaughterSylvia Whippopage 1 When We Wore Canoes On Our ShouldersMandy Watsonpage 2 This Is Not A Poem About GrandpaJake Tolbertpage 3 Old relationshipsBrandi Kinneypage 5 UntitledErin Winnerpage 6 BraverySylvia Whippopage 6 deep dark closetNicole Smithpage 7 Belly EarthTara Coburnpage 9 The River and FireJake Tolbertpage 10 UntitledAutumn Williamspage 12 Action PotentialKim Evanspage 13 Chimerical (a song for children)D.M. Attrapepage 14 UntitledAutumn Williamspage 16 UntitledMatthew Armstrongpage 18 Building YouSylvia Whippopage 19 RunningKim Evanspage 20 Walking Jenn to WorkJake Tolbertpage 22 Looking InKim Hunterpage 23 Void Between Me and WisconsinMandy Watsonpage 24 Artwork UntitledWendy Finchpage 4 MeditationJennifer Lundpage 8 UntitledSteve Drakepage 15 MemoriesJennifer Lundpage 21 UntitledKathryn Kolasinskipage 25 Prose FoundKim Hunterpage 26 A Day in the Life of William Baxter, DriverDaniel Fitzgeraldpage 32https://thekeep.eiu.edu/vehicle/1072/thumbnail.jp

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Awareness and Preferences Regarding BRCA1/2 Genetic Counseling and Testing Among Latinas and Non-Latina White Women at Increased Risk for Hereditary Breast and Ovarian Cancer

Abstract available at publisher's web site