Hemodynamic variability and cerebrovascular control after transient cerebral ischemia

We investigated if hemodynamic variability, cerebral blood flow (CBF) regulation, and their interrelationships differ between patients with transient ischemic attack (TIA) and controls. We recorded blood pressure (BP) and bilateral middle cerebral artery flow velocity (MCAv) in a cohort of TIA patients (n = 17), and age?matched controls (n = 15). Spontaneous fluctuations in BP and MCAv were characterized by spectral power analysis, and CBF regulation was assessed by wavelet phase synchronization analysis in the very low? (0.02–0.07 Hz), low? (0.07–0.20 Hz), and high?frequency (0.20–0.40 Hz) ranges. Furthermore, cerebrovascular CO2 reactivity was assessed as a second metric of CBF regulation by inducing hypercapnia with 8% CO2 inhalation followed by hyperventilation driven hypocapnia. We found that TIA was associated with higher BP power (group effect, P < 0.05), but not MCAv power (P = 0.11). CBF regulation (assessed by wavelet phase synchronization and CO2 reactivity) was intact in patients (all P ? 0.075) across both hemispheres (all P ? 0.51). Pooled data (controls and affected hemisphere of patients) showed that BP and MCAv power were positively correlated at all frequency ranges (R2 = 0.20–0.80, all P < 0.01). Furthermore, LF phase synchronization index was a significant determinant of MCAv power (P < 0.05), while VLF and HF phase synchronization index, and TIA were not (all P ? 0.50). These results indicate that CBF stability and control is maintained in TIA patients, but BPV is markedly elevated. BPV attenuation may be an important therapeutic strategy for enhancing secondary stroke prevention in patients who suffer a TIA

Optogenetic inhibitor of the transcription factor CREB

Current approaches for optogenetic control of transcription do not mimic the activity of endogenous transcription factors, which act at numerous sites in the genome in a complex interplay with other factors. Optogenetic control of dominant negative versions of endogenous transcription factors provides a mechanism for mimicking the natural regulation of gene expression. Here we describe opto-DN-CREB, a blue light controlled inhibitor of the transcription factor CREB created by fusing the dominant negative inhibitor A-CREB to photoactive yellow protein (PYP). A light driven conformational change in PYP prevents coiled-coil formation between A-CREB and CREB, thereby activating CREB. Optogenetic control of CREB function was characterized in vitro, in HEK293T cells, and in neurons where blue light enabled control of expression of the CREB targets NR4A2 and c-Fos. Dominant negative inhibitors exist for numerous transcription factors; linking these to optogenetic domains offers a general approach for spatiotemporal control of native transcriptional events

Optogenetic inhibitor of the transcription factor CREB

Current approaches for optogenetic control of transcription do not mimic the activity of endogenous transcription factors, which act at numerous sites in the genome in a complex interplay with other factors. Optogenetic control of dominant negative versions of endogenous transcription factors provides a mechanism for mimicking the natural regulation of gene expression. Here we describe opto-DN-CREB, a blue light controlled inhibitor of the transcription factor CREB created by fusing the dominant negative inhibitor A-CREB to photoactive yellow protein (PYP). A light driven conformational change in PYP prevents coiled-coil formation between A-CREB and CREB, thereby activating CREB. Optogenetic control of CREB function was characterized in vitro, in HEK293T cells, and in neurons where blue light enabled control of expression of the CREB targets NR4A2 and c-Fos. Dominant negative inhibitors exist for numerous transcription factors; linking these to optogenetic domains offers a general approach for spatiotemporal control of native transcriptional events

Reduced fire severity offers near-term buffer to climate-driven declines in conifer resilience across the western United States

Increasing fire severity and warmer, drier postfire conditions are making forests in the western United States (West) vulnerable to ecological transformation. Yet, the relative importance of and interactions between these drivers of forest change remain unresolved, particularly over upcoming decades. Here, we assess how the interactive impacts of changing climate and wildfire activity influenced conifer regeneration after 334 wildfires, using a dataset of postfire conifer regeneration from 10,230 field plots. Our findings highlight declining regeneration capacity across the West over the past four decades for the eight dominant conifer species studied. Postfire regeneration is sensitive to high-severity fire, which limits seed availability, and postfire climate, which influences seedling establishment. In the near-term, projected differences in recruitment probability between low- and high-severity fire scenarios were larger than projected climate change impacts for most species, suggesting that reductions in fire severity, and resultant impacts on seed availability, could partially offset expected climate-driven declines in postfire regeneration. Across 40 to 42% of the study area, we project postfire conifer regeneration to be likely following low-severity but not high-severity fire under future climate scenarios (2031 to 2050). However, increasingly warm, dry climate conditions are projected to eventually outweigh the influence of fire severity and seed availability. The percent of the study area considered unlikely to experience conifer regeneration, regardless of fire severity, increased from 5% in 1981 to 2000 to 26 to 31% by mid-century, highlighting a limited time window over which management actions that reduce fire severity may effectively support postfire conifer regeneration. © 2023 the Author(s)

The effect of a cardiac rehabilitation programme on carotid stiffness and haemodynamic properties of patients diagnosed with a transient ischaemic attack : a pilot study : compiled by Brandon Woolley for the degree of Master of Health Science in Sport and Exercise Science from Massey University, Wellington

Arterial stiffness is associated with cardiovascular risk factors (e.g., hypertension, abnormal blood lipids and lipoproteins, physical inactivity and obesity) and the existence of atherosclerosis, and is identified as an independent risk factor for coronary artery disease and ischaemic stroke. The common carotid artery is the major conduit supplying blood to the brain is of particular interest. Research has demonstrated that interventions, which target the aforementioned risk factors, reduce the risk of occurring vascular events. The aims of this study were to 1) identify whether an 8-week cardiac rehabilitation programme reduces the stiffness of the common carotid artery, as determined by changes in arterial compliance, distensibility and stiffness index β, in transient ischaemic attack (TIA), and; 2) investigate the relationship between changes to arterial stiffness and haemodynamic properties of the common carotid artery. Eighteen male and female participants (mean ± SD; 65 ± 11 y, 1.72 ± 0.07 m, 85.6 ± 11.5 kg) recruited within a 14 day period following a TIA, volunteered to take part in the present study. Initial risk stratification assessments (i.e., cholesterol, glucose, ECG, etc) were completed prior to assessing arterial stiffness and haemodynamic properties. An ultrasound device was used to obtain arterial measures while participants were rested and in a supine position. Participants were then randomised to either an exercise (EX; 8-week intervention), or to a usual-care control (CON) condition. Identical vascular measures were obtained post-intervention. Results revealed a significant Test by Condition interaction for arterial compliance, distensibility and stiffness index β, and for compliance and distensibility following the 8-week exercise intervention (all P < 0.05). Post-hoc analysis demonstrated a significantly greater change in compliance and distensibility for the EX condition. No significant changes were observed in arterial haemodynamic properties or CAD risk stratification measures. The present study has demonstrated that exercise leads to improved vascular health, as determined by a decrease in arterial stiffness, thus potentially leading to a reduced risk of an ensuing or recurring cardio- or cerebrovascular event

The effect of estimation and production procedures on running economy in recreational athletes

ObjectivesRunning economy is an important component in any endurance event. However, the influence of effort perception on running economy has yet to be examined.DesignThe purpose of this study was to assess the oxygen cost of running (running economy) at identical ratings of perceived exertion (RPE) during estimation (EST) and production (PR) procedures, during treadmill exercise.MethodsFourteen, well-trained male participants actively produced (self-regulated) a range of submaximal exercise intensities equating to RPE values 9, 11, 13, 15 and 17, and passively estimated their perception of exertion during an incremental graded-exercise test (GXT). Allometric scaling was used to ensure an appropriate comparison in running economy between conditions.ResultsThe present study demonstrated that the overall running economy between conditions was statistically similar (p &gt; 0.05). A significant interaction was however identified between Conditions and RPE (p &lt; 0.001). The interaction revealed that running economy significantly improved during PR but remained fairly consistent during EST between moderate and high perceptions of exertion (RPE 11–17). Despite similarities in running economy between conditions, physiological (oxygen uptake, heart rate, minute ventilation and blood lactate) and physical (running velocity) markers of exercise intensity were significantly higher during EST for equivalent perceptions of exertion (all p &lt; 0.05).ConclusionsPassive estimation procedures may improve running economy and enhance athletic performance when compared to identical perceptions of exertion elicited during active production procedures. Athletes, coaches and physical trainers should consider the perceptual procedures utilised during training to ensure that an athlete trains at the most effective training intensity

A randomized controlled trial to assess the psychosocial effects of early exercise engagement in patients diagnosed with transient ischaemic attack and mild, non-disabling stroke.

OBJECTIVE:To examine the effect of an early exercise and education programme on psychosocial health of transient ischaemic attack (TIA) and mild, non-disabling stroke patients.DESIGN:Randomized, parallel-group, clinical trial.SETTING:Hospital and academic institution.PARTICIPANTS:A total of 55 newly diagnosed transient ischaemic attack/mild stroke patients (Mean[SD]; 69[11]y).INTERVENTION:Participants were randomized to either an eight-week, twice weekly, 90-minute exercise and education programme (experimental group) or to a usual care control group.MAIN MEASURES:Psychosocial measures (SF-36, Hospital Anxiety and Depression Scale, Profile of Mood States, International Physical Activity Questionnaire, Stroke Awareness Questionnaire) were assessed at baseline and eight-week and 12-month follow-up.RESULTS:The experimental group demonstrated improvements in the Physical Component Score (Mean[SD]; 44.1[11.7] to 47.4[11.3]%), Vitality (46.5[12.4] to 54.2[14.2]%), Physical Functioning (45.6[10.7] to 51.9[14.7]%), Role Physical (38.7[10.8] to 43.1[13.6]%) and Global Health (49.1[10.3] to 54.4[13.6]%) from the SF-36, at the eight-week follow-up assessment (P?&lt;?0.05). There were no further changes in these measures between the eight-week and 12-month follow-up assessment (P?&gt;?0.05). The experimental group demonstrated a greater awareness of the signs and symptoms associated with stroke (P?&lt;?0.05). There were no differences in the Mental Component Score (SF-36), the Hospital Anxiety and Depression Scale or the International Physical Activity Questionnaire between treatment groups (P?&gt;?0.05).CONCLUSION:Early engagement in an exercise and education programme may improve physical health perceptions in transient ischaemic attack/mild stroke patients. However, secondary prevention exercise and education programmes warrant further research with regards to their effects on perceptions of mental health in this population group

The long-term effect of exercise on vascular risk factors and aerobic fitness in those with transient ischaemic attack: a randomized controlled trial

OBJECTIVE:Exercise has beneficial effects on vascular risk factors in transient ischaemic attack (TIA) patients within the sub-acute phase. This study examined whether TIA patients randomized to an early exercise and education programme within 2 weeks of TIA diagnosis would demonstrate improvements in cardiovascular risk factors and aerobic fitness 12 months post-diagnosis compared with control patients.METHODS:A single-centre, randomized, parallel-group clinical trial. Sixty TIA patients (69?±?11 years) completed a vascular risk stratification baseline assessment and a physical fitness examination. Individuals were randomized to either an 8-week early exercise and education group or control group. Fifty-one patients attended post-intervention assessments that were completed immediately (post-intervention) and 12 months after (12PI).RESULTS:A significantly greater improvement in resting SBP was observed between baseline and post-intervention for EX than for CON (-11?mmHg cf. -1?mmHg, respectively; P?&lt;?0.05). The improvement in SBP was maintained between post-intervention and 12PI (P?&gt;?0.05). Similar findings were demonstrated for BMI, bodyweight and peak oxygen uptake (P?&lt;?0.05). Exercise blood pressure, pulse pressure and double product (SBP?x?heart rate; an indication of myocardial workload) were significantly lower at post-intervention and 12PI for EX than for CON (all P?&lt;?0.05).CONCLUSION:An 8-week exercise programme soon after TIA resulted in beneficial changes in resting and exercise blood pressure that were maintained for 12 months