Optimizing Recruitment Strategies and Physician Engagement for Stroke Recovery Research.

BACKGROUND AND PURPOSE: A major challenge for stroke rehabilitation and recovery research is the recruitment and retention of participants. Our prior challenges and successes have influenced our team to rethink our approach and the potential for large-scale stroke recruitment. SUMMARY OF KEY POINTS: In this special interest article, we highlight how the adoption and implementation of recruitment strategies such as physician engagement and a streamlined "customer service" approach helped us improve our enrollment and maximize efficiency. Another positive outcome of enrollment was increased representation of those who identify as underrepresented minority or live in rural areas. RECOMMENDATIONS FOR CLINICAL PRACTICE: Rethinking our recruitment processes and infrastructure allowed for greater interprofessional interactions, minimal burden for our stroke physician team members, and maximized enrollment into our stroke studies.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A324).

The Effect of Stroke on Middle Cerebral Artery Blood Flow Velocity Dynamics During Exercise.

BACKGROUND AND PURPOSE: Previous work demonstrates that older adults have a lower response in the middle cerebral artery velocity (MCAv) to an acute bout of moderate-intensity exercise when compared with young adults. However, no information exists regarding MCAv response to exercise after stroke. We tested whether MCAv response to an acute bout of moderate-intensity exercise differed between participants 3 months after stroke and an age- and sex-matched control group of older adults (CON). A secondary objective was to compare MCAv response between the stroke- and non-stroke-affected MCAv. METHODS: Using transcranial Doppler ultrasound, we recorded MCAv during a 90-second baseline (BL) followed by a 6-minute moderate-intensity exercise bout using a recumbent stepper. Heart rate (HR), end-tidal CO2 (PETCO2), and beat-to-beat mean arterial blood pressure (MAP) were additional variables of interest. The MCAv response measures included BL, peak response amplitude (Amp), time delay (TD), and time constant (τ). RESULTS: The Amp was significantly lower in the stroke-affected MCAv compared with CON (P < 0.01) and in the nonaffected MCAv compared with CON (P = 0.03). No between-group differences were found between TD and τ. No significant differences were found during exercise for PETCO2 and MAP while HR was lower in participants with stroke (P < 0.01). Within the group of participants with stroke, no differences were found between the stroke-affected and non-stroke-affected sides for any measures. DISCUSSION AND CONCLUSIONS: Resolution of the dynamic response profile has the potential to increase our understanding of the cerebrovascular control mechanisms and test cerebrovascular response to physical therapy-driven interventions such as exercise.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A284).

Exercise intensity and middle cerebral artery dynamics in humans.

Despite its necessity for understanding healthy brain aging, the influence of exercise intensity on cerebrovascular kinetics is currently unknown. We, therefore characterized middle cerebral artery blood flow velocity (MCAv) kinetics associated with two exercise intensities: low and moderate. We hypothesized that increasing exercise intensity would increase the MCAv amplitude response (Amp) and that age and estimated fitness (V̇O2max) would be related to Amp. Baseline (BL) values were collected for 90-seconds followed by a 6-minute exercise bout. Heart rate, end-tidal CO2, mean arterial pressure and MCAv were recorded throughout. MCAv kinetics were described by Amp, time delay (TD) and time constant (τ). Sixty-four adults completed the study. Amp was greater during moderate compared to low exercise intensity (p < 0.001) while no difference was observed in either TD (p = 0.65) or τ (p = 0.47). Amp was negatively associated with age (p < 0.01) and positively correlated with estimated V̇O2max (p < 0.01). Although Amp declines with age, maintaining higher V̇O2max may benefit the cerebrovascular response to exercise.

Differential microRNA expression in human placentas of term intra-uterine growth restriction that regulates target genes mediating angiogenesis and amino acid transport.

Placental insufficiency leading to intrauterine growth restriction (IUGR) demonstrates perturbed gene expression affecting placental angiogenesis and nutrient transfer from mother to fetus. To understand the post-transcriptional mechanisms underlying such placental gene expression changes, our objective was to identify key non-coding microRNAs that express biological function. To this end, we initially undertook microarrays targeting microRNAs in a small sub-set of placentas of appropriate (AGA) versus small for gestational age (SGA) weight infants, and observed up-regulation of 97 miRs and down-regulation of 44 miRs in SGA versus AGA. In a larger cohort of samples (AGA, n = 21; SGA, n = 11; IUGR subset, n = 5), we validated by qRT-PCR differential expression of three specific microRNAs (miR-10b, -363 and -149) that target genes mediating angiogenesis and nutrient transfer. Validation yielded an increase in miR-10b and -363 expression of ~2.5-fold (p<0.02 each) in SGA versus AGA, and of ~3-fold (p<0.005) in IUGR versus AGA, with no significant change despite a trending increase in miR-149. To further establish a cause-and-effect paradigm, employing human HTR8 trophoblast cells, we assessed the effect of nutrient deprivation on miR expression and inhibition of endogenous miRs on target gene expression. In-vitro nutrient deprivation (~50%) increased the expression of miR-10b and miR-149 by 1.5-fold (p<0.02) while decreasing miR-363 (p<0.0001). Inhibition of endogenous miRs employing antisense sequences against miR-10b, -363 and -149 revealed an increase respectively in the expression of the target genes KLF-4 (transcription factor which regulates angiogenesis), SNAT1 and 2 (sodium coupled neutral amino acid transporters) and LAT2 (leucine amino acid transporter), which translated into a similar change in the corresponding proteins. Finally to establish functional significance we performed dual-luciferase reporter assays with 3'-insertion of miR-10b alone and observed a ~10% reduction in the 5'-luciferase activity versus the control. Lastly, we further validated by microarray and employing MirWalk software that the pathways and target genes identified by differentially expressed miRs in SGA/IUGR compared to AGA are consistent in a larger cohort. We have established the biological significance of various miRs that target common transcripts mediating pathways of importance, which are perturbed in the human IUGR placenta.