Impact of handgrip exercise intensity on brachial artery flow-mediated dilation.

PURPOSE: Previous studies that have examined the impact of exercise intensity on conduit artery endothelial function have involved large muscle group exercise which induces local and systemic effects. The aim of this study was to examine flow-mediated dilation (FMD) before and after incremental intensities of handgrip exercise (HE), to assess the role of local factors such as blood flow and shear rate on post-exercise brachial artery function. METHODS: Eleven healthy men attended the laboratory on three occasions. Subjects undertook 30 min of handgrip exercise at three intensities (5, 10 or 15 % MVC). Brachial artery FMD, shear and blood flow patterns were examined before, immediately after and 60 min post exercise. RESULTS: Handgrip exercise increased mean and antegrade shear rate (SR) and blood flow (BF) and reduced retrograde SR and BF (all P < 0.01). Exercise intensity was associated with a dose-dependent increase in both mean and antegrade BF and SR (interaction, P < 0.01). Post-hoc tests revealed that, whilst handgrip exercise did not immediately induce post-exercise changes, FMD was significantly higher 60 min post-exercise following the highest exercise intensity (5.9 ± 2.8-10.4 ± 5.8 %, P = 0.01). CONCLUSIONS: Handgrip exercise leads to intensity-and time-dependent changes in conduit artery function, possibly mediated by local increases in shear, with improvement in function evident at 1 h post-exercise when performed at a higher intensity

Evidence for Shear Stress-Mediated Dilation of the Internal Carotid Artery in Humans.

Increases in arterial carbon dioxide tension (hypercapnia) elicit potent vasodilation of cerebral arterioles. Recent studies have also reported vasodilation of the internal carotid artery during hypercapnia, but the mechanism(s) mediating this extracranial vasoreactivity are unknown. Hypercapnia increases carotid shear stress, a known stimulus to vasodilation in other conduit arteries. To explore the hypothesis that shear stress contributes to hypercapnic internal carotid dilation in humans, temporal changes in internal and common carotid shear rate and diameter, along with changes in middle cerebral artery velocity, were simultaneously assessed in 18 subjects at rest and during hypercapnia (6% carbon dioxide). Middle cerebral artery velocity increased significantly (69±10-103±17 cm/s; P<0.01) along with shear in both the internal (316±52-518±105 1/s; P<0.01) and common (188±40-275±61 1/s; P<0.01) carotids. Diameter also increased (P<0.01) in both carotid arteries (internal: +6.3±2.9%; common: +5.8±3.0%). Following hypercapnia onset, there was a significant delay between the onset of internal carotid shear (22±12 seconds) and diameter change (85±51 seconds). This time course is associated with shear-mediated dilation of larger conduit arteries in humans. There was a strong association between change in shear and diameter of the internal carotid (r=0.68; P<0.01). These data indicate, for the first time in humans, that shear stress is an important stimulus for hypercapnic vasodilation of the internal carotid artery. The combination of a hypercapnic stimulus and continuous noninvasive, high-resolution assessment of internal carotid shear and dilation may provide novel insights into the function and health of the clinically important extracranial arteries in humans

Reproducibility of four frequently used local heating protocols to assess cutaneous microvascular function.

BACKGROUND: Skin microvascular responses to local heating are frequently used to assess microvascular function. Several local heating protocols have been developed, all varying slightly in execution. The aim of this study was to determine the inter-day reproducibility of the four most commonly used local heating protocols in healthy young subjects. METHODS: Fifteen, healthy males (28±5yrs, BMI 25±2kg/m(2)) attended two experimental trials 2-7days apart. During each trial, baseline and maximal thermally stimulated forearm skin responses were examined simultaneously at four sites on the dominant forearm using laser Doppler flowmetry (LDF). The following heating protocols were adopted: 1. Rapid 39°C (0.5°C/5s), 2. Rapid 42°C (0.5°C/5s) 3. Gradual 42°C (0.5°C/2min 30s) and 4. Slow 42°C (0.5°C/5min). The coefficient of variation (CV) was calculated for absolute flux, cutaneous vascular conductance (CVC; flux/mean arterial pressure, MAP) and CVC expressed as a percentage of maximal CVC at 44°C (%CVCmax) at three different time points; baseline (33°C), plateau (39/42°C) and maximal (44°C). RESULTS: Reproducibility of baseline flux, CVC and %CVCmax was 17-29% across all protocols. During the plateau, Rapid, Gradual and Slow 42°C demonstrated a reproducibility of 13-18% for flux and CVC and 5-11% for %CVCmax. However, Rapid 39°C demonstrated a lower reproducibility for flux, CVC and %CVCmax (all 21%). Reproducibility at 44°C was 12-15% for flux and CVC across all protocols. CONCLUSION: This is the first study examining inter-day reproducibility across four local heating protocols. The good-to-moderate reproducibility of the Rapid, Gradual and Slow 42°C protocols support their (simultaneous) use to assess microvascular function. Using Rapid 39°C may require a greater number of subjects to detect differences within subjects

A database of whole-body action videos for the study of action, emotion, and untrustworthiness

We present a database of high-definition (HD) videos for the study of traits inferred from whole-body actions. Twenty-nine actors (19 female) were filmed performing different actions—walking, picking up a box, putting down a box, jumping, sitting down, and standing and acting—while conveying different traits, including four emotions (anger, fear, happiness, sadness), untrustworthiness, and neutral, where no specific trait was conveyed. For the actions conveying the four emotions and untrustworthiness, the actions were filmed multiple times, with the actor conveying the traits with different levels of intensity. In total, we made 2,783 action videos (in both two-dimensional and three-dimensional format), each lasting 7 s with a frame rate of 50 fps. All videos were filmed in a green-screen studio in order to isolate the action information from all contextual detail and to provide a flexible stimulus set for future use. In order to validate the traits conveyed by each action, we asked participants to rate each of the actions corresponding to the trait that the actor portrayed in the two-dimensional videos. To provide a useful database of stimuli of multiple actions conveying multiple traits, each video name contains information on the gender of the actor, the action executed, the trait conveyed, and the rating of its perceived intensity. All videos can be downloaded free at the following address: http://www-users.york.ac.uk/~neb506/databases.html. We discuss potential uses for the database in the analysis of the perception of whole-body actions

Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD:implication for COPD-associated neuropathogenesis

The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD

A promising method for identifying cross-cultural differences in patient perspective: the use of Internet-based focus groups for content validation of new Patient Reported Outcome assessments

OBJECTIVES: This proof of concept (POC) study was designed to evaluate the use of an Internet-based bulletin board technology to aid parallel cross-cultural development of thematic content for a new set of patient-reported outcome measures (PROs). METHODS: The POC study, conducted in Germany and the United States, utilized Internet Focus Groups (IFGs) to assure the validity of new PRO items across the two cultures – all items were designed to assess the impact of excess facial oil on individuals' lives. The on-line IFG activities were modeled after traditional face-to-face focus groups and organized by a common 'Topic' Guide designed with input from thought leaders in dermatology and health outcomes research. The two sets of IFGs were professionally moderated in the native language of each country. IFG moderators coded the thematic content of transcripts, and a frequency analysis of code endorsement was used to identify areas of content similarity and difference between the two countries. Based on this information, draft PRO items were designed and a majority (80%) of the original participants returned to rate the relative importance of the newly designed questions. FINDINGS: The use of parallel cross-cultural content analysis of IFG transcripts permitted identification of the major content themes in each country as well as exploration of the possible reasons for any observed differences between the countries. Results from coded frequency counts and transcript reviews informed the design and wording of the test questions for the future PRO instrument(s). Subsequent ratings of item importance also deepened our understanding of potential areas of cross-cultural difference, differences that would be explored over the course of future validation studies involving these PROs. CONCLUSION: The use of IFGs for cross-cultural content development received positive reviews from participants and was found to be both cost and time effective. The novel thematic coding methodology provided an empirical platform on which to develop culturally sensitive questionnaire content using the natural language of participants. Overall, the IFG responses and thematic analyses provided a thorough evaluation of similarities and differences in cross-cultural themes, which in turn acted as a sound base for the development of new PRO questionnaires

MicroRNAs in pulmonary arterial remodeling

Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH

C4 photosynthesis boosts growth by altering physiology, allocation and size.

C4 photosynthesis is a complex set of leaf anatomical and biochemical adaptations that have evolved more than 60 times to boost carbon uptake compared with the ancestral C3 photosynthetic type(1-3). Although C4 photosynthesis has the potential to drive faster growth rates(4,5), experiments directly comparing C3 and C4 plants have not shown consistent effects(1,6,7). This is problematic because differential growth is a crucial element of ecological theory(8,9) explaining C4 savannah responses to global change(10,11), and research to increase C3 crop productivity by introducing C4 photosynthesis(12). Here, we resolve this long-standing issue by comparing growth across 382 grass species, accounting for ecological diversity and evolutionary history. C4 photosynthesis causes a 19-88% daily growth enhancement. Unexpectedly, during the critical seedling establishment stage, this enhancement is driven largely by a high ratio of leaf area to mass, rather than fast growth per unit leaf area. C4 leaves have less dense tissues, allowing more leaves to be produced for the same carbon cost. Consequently, C4 plants invest more in roots than C3 species. Our data demonstrate a general suite of functional trait divergences between C3 and C4 species, which simultaneously drive faster growth and greater investment in water and nutrient acquisition, with important ecological and agronomic implications

Outcomes associated with matching patients' treatment preferences to physicians' recommendations: study methodology

<p>Abstract</p> <p>Background</p> <p>Patients often express strong preferences for the forms of treatment available for their disease. Incorporating these preferences into the process of treatment decision-making might improve patients' adherence to treatment, contributing to better outcomes. We describe the methodology used in a study aiming to assess treatment outcomes when patients' preferences for treatment are closely matched to recommended treatments.</p> <p>Method</p> <p>Participants included patients with moderate and severe psoriasis attending outpatient dermatology clinics at the University Medical Centre Mannheim, University of Heidelberg, Germany. A self-administered online survey used conjoint analysis to measure participants' preferences for psoriasis treatment options at the initial study visit. Physicians' treatment recommendations were abstracted from each participant's medical records. The Preference Matching Index (PMI), a measure of concordance between the participant's preferences for treatment and the physician's recommended treatment, was determined for each participant at t₁(initial study visit). A clinical outcome measure, the Psoriasis Area and Severity Index, and two participant-derived outcomes assessing treatment satisfaction and health related quality of life were employed at t₁, t₂(twelve weeks post-t₁) and t₃(twelve weeks post-t₂). Change in outcomes was assessed using repeated measures analysis of variance. The association between participants' PMI scores at t₁and outcomes at t₂and t₃was evaluated using multivariate regressions analysis.</p> <p>Discussion</p> <p>We describe methods for capturing concordance between patients' treatment preferences and recommended treatment and for assessing its association with specific treatment outcomes. The methods are intended to promote the incorporation of patients' preferences in treatment decision-making, enhance treatment satisfaction, and improve treatment effectiveness through greater adherence.</p