Jacob E. Matney

Rapid onset vasodilation (ROV) is the immediate, transient increase in muscle blood flow following contraction and is mediated by chemical, mechanical, and, potentially, neural mechanisms. Although exercise training has been shown to preserve ROV in older adults, it remains unclear whether training promotes adaptation in specific contributing mechanisms. This study tested the hypothesis that a history of forearm training increases ROV. Sixteen healthy young males (8 trained, 8 sedentary) completed two trials of 1s voluntary forearm contractions (5, 10, 15kg; 20% and 100% of maximal voluntary contraction), electrically-stimulated involuntary contractions (5 and 10mA), and mechanical forearm compression (50, 200, 300mmHg) (randomly ordered). Forearm blood flow (ultrasound) and mean arterial pressure (finger photoplethysmography) were measured beat-to-beat and used to calculate Forearm vascular conductance (FVC). Data from the two trials of each contraction/compression were averaged together to form a singular response. Forearm and hand lean mass, as measured via dual-energy X-ray absorptiometry (DXA), did not differ between groups. Trained participants displayed greater absolute ROV responses to voluntary and involuntary contractions (p ≤ 0.05 for all), as well as to higher-intensity mechanical compressions (p ≤ 0.05 for 300mmHg ΔFVC _total , 200mmHg and 300mmHg ΔFVC _peak ). Additionally, ROV responses increased disproportionately with absolute voluntary contraction intensity in trained participants (Training Status x Intensity interaction ΔFVC _total : p = 0.02, η _p ² = 0.29). These findings extend upon previous research which has demonstrated training-related preservation of ROV and indicate that exercise training enhances rapid vascular responsiveness across multiple stimulus modalities, providing new insight into training-induced adaptations in vascular regulation.

Cerebrovascular CYP450 is underexplored in humans. Twenty‐three participants (12 females) completed familiarization and two experimental visits utilizing double‐blind, randomized, crossover design. Participants ingested fluconazole (150 mg; FLZ, CYP450 inhibitor) or placebo (PLC, microcrystalline cellulose) followed by 120 min of supine rest. Five minutes of middle cerebral artery velocity (MCAv) and mean arterial pressure (MAP) were collected during rest (PLC/FLZ _BASE ) and lower body negative pressure (LBNP; −20 mmHg; PLC/FLZ _LBNP ). There was no interaction for MCAv, cerebrovascular conductance index (CVCi), resistance area product (RAP), critical closing pressure (CrCP), or transfer function variables. Bonferroni tests revealed only FLZ attenuated MCAv (FLZ _BASE 75.2 ± 11.3 cm•s ⁻¹ vs. FLZ _LBNP 70.6 ± 11.2 cm•s ⁻¹ , p = 0.015, d = 0.713) and CVCi (FLZ _BASE 0.76 ± 0.12 cm•s ⁻¹ •mmHg ⁻¹ vs. FLZ _LBNP 0.71 ± 0.11 cm•s ⁻¹ •mmHg ⁻¹ , p = 0.003, d = 0.865) during LBNP. LBNP lowered CrCP (PLC _BASE 29.7 ± 9.3 mmHg vs. PLC _LBNP 25.1 ± 11.3 mmHg, p = 0.002, d = 0.940) within PLC. RAP increased during LBNP (PLC _BASE 0.96 ± 0.29 vs. PLC _LBNP 1.08 ± 0.32, p = < 0.001, d = 1.28; FLZ _BASE 0.98 ± 0.24 vs. FLZ _LBNP 1.07 ± 0.23, p = < 0.001, d = 1.10). These data suggest a participatory, nonobligatory role of CYP450 in human cerebrovascular control.

Background: The US cancer survivor population is projected to hit 26M by 2040. Chemotherapy is an effective cancer treatment, but can diminish cancer survivors’ quality of life—particularly cognitive function—through select pathophysiological processes, including immune system and antioxidant dysregulation. The resulting cytokine release can impair cerebrovascular function—likely contributing to chemotherapy-induced cognitive impairment (CICI; “chemo-brain”). Type 2 diabetes mellitus (T2DM)—a common cancer survivor comorbidity—shares underlying pathophysiology with CICI. Cancer survivors with T2DM might thus have a higher CICI risk than those without T2DM. Physical activity (PA) counteracts CICI’s and T2DM’s pathophysiology, but little to no research has been conducted assessing the impact of PA on this joint pathophysiology. Objective: To compare cerebrovascular and cognitive function as well as proinflammatory, cardiometabolic, epigenetic, and psychosocial outcomes between ancer survivors with and without T2DM pre- to postengagement in a 12-week technology-based PA program grounded in the Social Cognitive Theory. We hypothesize that cancer survivors with and without T2DM will demonstrate similar pre to poststudy improvements in psychosocial outcomes, but that changes in cerebrovascular and cardiometabolic outcomes, as well as PA engagement, will be greater for cancer survivors with T2DM. We also believe that each group will have distinct epigenetic profiles that will change pre to poststudy. Methods: We are conducting a 30-participant pilot study in cancer survivors with (n=15) and without (n=15) T2DM—all of whom report currently experiencing “chemo-brain.” To account for attrition, we are recruiting 38 cancer survivors from Oklahoma City, OK, and the surrounding area. Among the most important eligibility criteria are the self-report of cognitive difficulties following primary cancer treatment, being ≥18 years old, being within 3 years of primary cancer treatment, and not meeting nationally recommended PA guidelines. Participants receive 2 smartphone apps. One smartphone app provides health education and the ability to set goals and journal about their wellness journey. The other provides a workout program continually tailored to each participant via their communication with the study exercise physiologist, with resistance bands and a wearable device provided to support the program. At Baseline and Poststudy, we assess cerebrovascular function (transcranial doppler [TCD]), cognition (National Institutes of Health Toolbox), cardiometabolic outcomes (venipuncture), and epigenetics (saliva collection). Participants also wear accelerometers at Baseline and Poststudy to objectively assess PA, with Baseline, Midpoint, and Poststudy surveys assessing psychosocial outcomes. We will use t tests and chi-square tests to assess baseline differences and repeated-measures ANCOVA to assess changes over time. Results: Participant recruitment started in March 2025, and we expect to recruit until late 2026. We will begin analyzing baseline data in 2026. Conclusions: Successful study completion will provide valuable insights into the remote delivery of PA-oriented supportive care for cancer survivors experiencing chemo-brain, as well as how T2DM and PA contribute to the mechanistic underpinnings of chemo-brain. Trial Registration: ClinicalTrials.gov NCT06725953; https://clinicaltrials.gov/study/NCT06725953 International Registered Report Identifier (IRRID): DERR1-10.2196/79739

This study demonstrates that inhibiting CYP2C9 significantly reduces brachial artery flow-mediated dilation (FMD) in young, healthy adults, implicating CYP2C9-derived metabolites as a mediator of endothelium-dependent vasodilation. Notably, CYP2C9 inhibition attenuated FMD in males, whereas females maintained their vasodilatory response, suggesting sex-specific reliance on CYP2C9 signaling. These findings enhance our understanding of sex differences in vascular regulation and may inform future strategies for preserving endothelial health.

BACKGROUND The US cancer survivor population is projected to hit 26M by 2040. Chemotherapy is an effective cancer treatment, but can diminish cancer survivors’ quality of life—particularly cognitive function—through select pathophysiological processes, including immune system and antioxidant dysregulation. The resulting cytokine release can impair cerebrovascular function—likely contributing to chemotherapy-induced cognitive impairment (CICI; “chemo-brain”). Type 2 diabetes mellitus (T2DM)—a common cancer survivor comorbidity—shares underlying pathophysiology with CICI. Cancer survivors with T2DM might thus have a higher CICI risk than those without T2DM. Physical activity (PA) counteracts CICI’s and T2DM’s pathophysiology, but little to no research has been conducted assessing the impact of PA on this joint pathophysiology. OBJECTIVE To compare cerebrovascular and cognitive function as well as proinflammatory, cardiometabolic, epigenetic, and psychosocial outcomes between ancer survivors with and without T2DM pre- to postengagement in a 12-week technology-based PA program grounded in the Social Cognitive Theory. We hypothesize that cancer survivors with and without T2DM will demonstrate similar pre to poststudy improvements in psychosocial outcomes, but that changes in cerebrovascular and cardiometabolic outcomes, as well as PA engagement, will be greater for cancer survivors with T2DM. We also believe that each group will have distinct epigenetic profiles that will change pre to poststudy. METHODS We are conducting a 30-participant pilot study in cancer survivors with (n=15) and without (n=15) T2DM—all of whom report currently experiencing “chemo-brain.” To account for attrition, we are recruiting 38 cancer survivors from Oklahoma City, OK, and the surrounding area. Among the most important eligibility criteria are the self-report of cognitive difficulties following primary cancer treatment, being ≥18 years old, being within 3 years of primary cancer treatment, and not meeting nationally recommended PA guidelines. Participants receive 2 smartphone apps. One smartphone app provides health education and the ability to set goals and journal about their wellness journey. The other provides a workout program continually tailored to each participant via their communication with the study exercise physiologist, with resistance bands and a wearable device provided to support the program. At Baseline and Poststudy, we assess cerebrovascular function (transcranial doppler [TCD]), cognition (National Institutes of Health Toolbox), cardiometabolic outcomes (venipuncture), and epigenetics (saliva collection). Participants also wear accelerometers at Baseline and Poststudy to objectively assess PA, with Baseline, Midpoint, and Poststudy surveys assessing psychosocial outcomes. We will use t tests and chi-square tests to assess baseline differences and repeated-measures ANCOVA to assess changes over time. RESULTS Participant recruitment started in March 2025, and we expect to recruit until late 2026. We will begin analyzing baseline data in 2026. CONCLUSIONS Successful study completion will provide valuable insights into the remote delivery of PA-oriented supportive care for cancer survivors experiencing chemo-brain, as well as how T2DM and PA contribute to the mechanistic underpinnings of chemo-brain. CLINICALTRIAL ClinicalTrials.gov NCT06725953; https://clinicaltrials.gov/study/NCT06725953 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/79739