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Breast cancer (BC) is one of the most prevalent forms of cancer in women worldwide. Clinical research indicates that BC patients are at an increased risk for thrombotic events, drastically decreasing their quality-of-life and treatment outcomes. There is ample evidence of this in the literature, but it is mainly focused on metastatic BC. Therefore, coagulopathies of nonmetastatic BC are understudied and require in-depth investigation. In this study, clot kinetics and ultrastructure were used to investigate treatment-naïve, nonmetastatic BC patients using scanning electron microscopy, Thromboelastography®, and confocal laser scanning microscopy. It was demonstrated that nonmetastatic BC patients exhibit minimal ultrastructural alterations of the clot components and no changes in the clot kinetics. However, BC patients presented changes to fibrinogen protein structure, compared to matched controls, using an amyloid-selective stain. Together, these findings suggest that coagulation dysfunction(s) in BC patients with early disease manifest at the microlevel, rather than the macrolevel. This study presents novel insights to a method that are more sensitive to coagulation changes in this specific patient group, emphasizing that the coagulation system may react in different forms to the disease, depending on the progression of the disease itself.

We sought to assess the accuracy of current or developing new prediction equations for resting metabolic rate (RMR) in adolescent athletes. RMR was assessed via indirect calorimetry, alongside known predictors (body composition via dual-energy X-ray absorptiometry, height, age, and sex) and hypothesized predictors (race and maturation status assessed via years to peak height velocity), in a diverse cohort of adolescent athletes (n = 126, 77% male, body mass = 72.8 ± 16.6 kg, height = 176.2 ± 10.5 cm, age = 16.5 ± 1.4 years). Predictive equations were produced and cross-validated using repeated k-fold cross-validation by stepwise multiple linear regression (10 folds, 100 repeats). Performance of the developed equations was compared with several published equations. Seven of the eight published equations examined performed poorly, underestimating RMR in >75% to >90% of cases. Root mean square error of the six equations ranged from 176 to 373, mean absolute error ranged from 115 to 373 kcal, and mean absolute error SD ranged from 103 to 185 kcal. Only the Schofield equation performed reasonably well, underestimating RMR in 51% of cases. A one- and two-compartment model were developed, both r2 of .83, root mean square error of 147, and mean absolute error of 114 ± 26 and 117 ± 25 kcal for the one- and two-compartment model, respectively. Based on the models’ performance, as well as visual inspection of residual plots, the following model predicts RMR in adolescent athletes with better precision than previous models; RMR = 11.1 × body mass (kg) + 8.4 × height (cm) − (340 male or 537 female).

Exercise capacity is frequently reduced in people with diabetes mellitus (DM), and the contribution of pulmonary microvascular dysfunction remains undefined. We hypothesized that pulmonary microvascular disease, measured by a novel exercise echocardiography technique termed pulmonary transit of agitated contrast (PTAC), would be greater in subjects with DM and that the use of pulmonary vasodilator agent sildenafil would improve exercise performance by reducing right ventricular afterload. Forty subjects with DM and 20 matched controls performed cardiopulmonary exercise testing and semisupine exercise echocardiography 1 h after placebo or sildenafil ingestion in a double-blind randomized crossover design. The primary efficacy end point was exercise capacity (V̇o2peak) while secondary measures included pulmonary vascular resistance, cardiac output, and change in PTAC. DM subjects were aged 44 ± 13 yr, 73% male, with 16 ± 10 yr DM history. Sildenafil caused marginal improvements in echocardiographic measures of biventricular systolic function in DM subjects. Exercise-induced increases in pulmonary artery systolic pressure and pulmonary vascular resistance were attenuated with sildenafil, while heart rate (+2.4 ±1.2 beats/min, P = 0.04) and cardiac output (+322 ± 21 ml, P = 0.03) improved. However, the degree of PTAC did not change ( P = 0.93) and V̇o2peak did not increase following sildenafil as compared with placebo (V̇o2peak: 31.8 ± 9.7 vs. 32.1 ± 9.5 ml·min−1·kg−1, P = 0.42). We conclude that sildenafil administration causes modest acute improvements in central hemodynamics but does not improve exercise capacity. This may be due to the mismatch in action of sildenafil on the pulmonary arteries rather than the distal pulmonary microvasculature and potential adverse effects on peripheral oxygen extraction. NEW & NOTEWORTHY This is one of the largest and most comprehensive studies of cardiopulmonary exercise performance in people with diabetes mellitus and to our knowledge the first to assess the effect of sildenafil using detailed echocardiographic measures during incremental exercise. Sildenafil attenuated the rise in pulmonary vascular resistance while augmenting cardiac output and intriguingly heart rate, without conferring any improvement in exercise capacity. The enhanced central hemodynamic indexes may have been offset by reduced peripheral O2 extraction.

The purpose of this study was to expand our previously published sweat normative data/analysis (n = 506) to establish sport-specific normative data for whole-body sweating rate (WBSR), sweat [Na+],...

Background & Aims:The initiation, development, and progression of many cancers, including colorectal cancer (CRC), are associated with environmental factors. A significant link exists between specific bacterial infections and cancer incidence, with a strong association between chronic infection, chronic inflammation and colorectal carcinogenesis. Recently, we reported significantly increased levels of lipopolysaccharide in CRC patient blood, compared to that of healthy individuals. By analysing CRC tumors, this study aims to contribute to the identification of (novel) markers/factors associated with CRC tumorigenesis.Methods: Colorectal tumor samples from newly diagnosed (histologically confirmed) CRC patients (n = 24) and morphologically normal colon biopsies (n = 10) were collected and analysed in a cross-sectional study. Immunohistochemistry protocols and statistical signal analysis were used to detect specific bacteria and proteins of interest in human colorectal tissue. Furthermore, the presence of structural protein changes in CRC tumor tissues, compared to control tissues, was investigated using the fluorescent amyloidselective Amytracker™ 630 marker and confocal microscopy.Results: We show an intratumor bacterial presence in CRC patients, with high levels of Escherichia coli strongly associated with CRC. High levels of intratumor serum amyloid A are also strongly associated with CRC. Furthermore, Helicobacter pylori is elevated, but to a smaller degree, and only when we account for data imbalance. We also report a significantly enhanced amyloid-specific fluorescence signal in CRC tumors, compared to control tissues.Conclusions: The role that infections play in a variety of cancers, including CRC, is increasingly recognized, and we provide evidence of a bacterial presence in CRC tumors. The analysis of CRC tumors, in addition to CRC blood, offers unique opportunities to investigate factors that may fuel colorectal carcinogenesis, and to ultimately identify novel markers that are associated with CRC.

Wearable microfluidic system enables remote analysis of sweat rate and chloride loss for assessing personalized fluid needs., Advanced capabilities in noninvasive, in situ monitoring of sweating rate and sweat electrolyte losses could enable real-time personalized fluid-electrolyte intake recommendations. Established sweat analysis techniques using absorbent patches require post-collection harvesting and benchtop analysis of sweat and are thus impractical for ambulatory use. Here, we introduce a skin-interfaced wearable microfluidic device and smartphone image processing platform that enable analysis of regional sweating rate and sweat chloride concentration ([Cl−]). Systematic studies (n = 312 athletes) establish significant correlations for regional sweating rate and sweat [Cl−] in a controlled environment and during competitive sports under varying environmental conditions. The regional sweating rate and sweat [Cl−] results serve as inputs to algorithms implemented on a smartphone software application that predicts whole-body sweating rate and sweat [Cl−]. This low-cost wearable sensing approach could improve the accessibility of physiological insights available to sports scientists, practitioners, and athletes to inform hydration strategies in real-world ambulatory settings.

ObjectiveThe risk of cardiovascular events in patients with RA is disproportionately heightened as a result of systemic inflammation. The relative effect of autoimmune-associated citrullination on the structure and thrombotic potential of fibrin(ogen) remains unknown. We therefore compared indices of vascular function, inflammation, coagulation and fibrin clot composition in RA patients with healthy controls and evaluated inter-parameter relationships.MethodsBlood samples were collected from 30 RA patients and 25 age- and gender-matched healthy volunteers. Levels of SAA, CRP, ICAM-1 and VCAM-1 was measured using a sandwich immunoassay. Whole blood coagulation was assessed using Thromboelastography. Fibrin clot networks and fiber structure was investigated using Scanning Electron Microscopy. The detection and quantification of citrullination in formed fibrin clots were performed using a fluorescently labeled Citrulline monoclonal antibody with Confocal Microscopy.ResultsConcentrations of SAA, CRP and ICAM-1 were significantly elevated in RA patients compared to controls. TEG parameters relating to coagulation initiation (R and K), rate of fibrin cross-linking (α-Angle), and time to reach maximum thrombus generation (TMRTG) were attenuated in RA patients. Parameters relating to clot strength (MA, MRTG, TGG) did not statistically differ between RA and controls. Logistic regression modelling revealed stronger association between acute phase reactants (CRP, SAA) with TEG parameters than endothelial function markers. Microscopic analysis revealed denser networks of thicker fibrin fibers in RA patients compared to controls [median (interquartile range) 214 (170-285)vs120 (100-144) nm respectively, pConclusionPatients with active RA display a coagulation profile that is dissimilar to general findings associated with other inflammatory conditions. The alteration of protein structures by autoimmune linked citrullination could play a role in determining the structure of fibrin and the potential of conferring a heightened thrombotic risk in RA patients.

Gut dysbiosis contributes to the development of a dysfunctional gut barrier, facilitating the translocation of bacteria and inflammagens, and is implicated in colorectal cancer (CRC) pathogenesis. Such ‘leaky gut’ conditions result in systemic inflammation, of which a hallmark is increased hypercoagulability. Fluorescence antibody confocal microscopy was used to determine circulating levels of lipopolysaccharide (LPS) in control and CRC populations. Here we showed that circulating levels of LPS are significantly elevated in the CRC population. We also showed that markers of inflammation and hypercoagulability are increased in this population. Furthermore, anomalous blood clotting and structural changes in blood components are presented. Importantly, the association between LPS levels, inflammation, and hematological dysfunction was analysed. Statistical regression models were applied to identify markers with strong association with CRC, and to investigate the correlation between markers. A core aim is enhanced biomarker discovery for CRC. We conclude that circulating LPS can promote systemic inflammation and contribute to the development of a pathological coagulation system, with resulting chronic inflammation and an activated coagulation system implicated in tumorigenesis. Blood-based screening tools are an emerging research area of interest for CRC screening. We propose the use of additional (novel) biomarkers to effectively screen for CRC.

We aimed to compare closed-loop glucose control for people with type 1 diabetes undertaking high-intensity interval exercise (HIIE) versus moderate-intensity exercise (MIE).Adults with type 1 diabetes established on insulin pumps undertook HIIE and MIE stages in random order during automated insulin delivery via a closed-loop system (Medtronic). Frequent venous sampling for glucose, lactate, ketones, insulin, catecholamines, cortisol, growth hormone, and glucagon levels was performed. The primary outcome was plasma glucose4.0 mmol/L for ≥15 min, from exercise commencement to 120 min postexercise. Secondary outcomes included continuous glucose monitoring and biochemical parameters.Twelve adults (age mean ± standard deviation 40 ± 13 years) were recruited; all completed the study. Plasma glucose of one participant fell to 3.4 mmol/L following MIE completion; no glucose levels were4.0 mmol/L for HIIE (primary outcome). There were no glucose excursions15.0 mmol/L for either stage. Mean (±standard error) plasma glucose did not differ between stages pre-exercise; was higher during exercise in HIIE than MIE (11.3 ± 0.5 mmol/L vs. 9.7 ± 0.6 mmol/L, respectively; P 0.001); and remained higher until 60 min postexercise. There were no differences in circulating free insulin before, during, or postexercise. During HIIE compared with MIE, there were greater increases in lactate (P 0.001), catecholamines (all P 0.05), and cortisol (P 0.001). Ketones increased more with HIIE than MIE postexercise (P = 0.031).Preliminary findings suggest that closed-loop glucose control is safe for people undertaking HIIE and MIE. However, the management of the postexercise rise in ketones secondary to counter-regulatory hormone-induced insulin resistance observed with HIIE may represent a challenge for closed-loop systems.

Background Exercise capacity is frequently reduced in people with diabetes mellitus (DM) and may be due to subclinical cardiac dysfunction. Speckle-tracking echocardiography is now widely available; however, the clinical utility and significance of left ventricular (LV) strain and twist parameters remain uncertain. We hypothesized that LV strain and twist would be reduced in DM subjects during exercise. Methods Adults with type 1 or type 2 DM and age- and sex-matched controls performed cardiopulmonary exercise testing (VO2 peak) and supine bicycle exercise echocardiography. Detailed echocardiographic assessment of biventricular function was performed at baseline and repeated during incremental exercise to maximal intensity. Results Of the 60 participants completing the study protocol, 51 (34 DM, 17 controls; mean age, 42 ± 13 years; 69% male; DM duration, 16 ± 10 years) had sufficient image quality to assess LV deformation and twist mechanics at rest. Of these, 38 (25 DM, 13 controls) were able to be assessed immediately after exercise. Baseline LV systolic and diastolic function using standard echocardiography measurements were similar between groups. Resting LV global longitudinal strain, twist, twist rate and untwist rate, and the corresponding peak exercise and reserve measures did not differ significantly. As compared with the control subjects, exercise capacity was reduced in the DM cohort (VO2 peak 33 ± 10 vs 41 ± 12 mL/minute/kg; P = .02); however, no correlation was observed between VO2 peak and LV twist reserve (R = 0.28, P = .09), LV twist rate reserve (R = 0.14, P = .39), or LV untwist rate reserve (R = 0.24, P = .14). Conclusions Despite reduced VO2 peak, LV twist mechanics at rest and after maximal intensity exercise did not differ significantly in a cohort of asymptomatic DM subjects with normal resting LV systolic and diastolic function compared with age- and sex-matched controls. This would suggest that exercise capacity can be reduced in the absence of subclinical cardiac dysfunction and that noncardiac factors should be considered as alternative explanations.

Background The global burden of type 2 diabetes mellitus (T2DM), together with the presence of cardiovascular risk in this population, is reaching pandemic levels. A prominent feature of T2DM is chronic and systemic inflammation, with the accompanying presence of circulating and dysregulated inflammatory biomarkers; which in turn is associated with abnormal clot formation. Methods Here, we investigate the correlation between abnormal blood clotting, using thromboelastography (TEG), clot ultrastructure using scanning electron microscopy (SEM) and the presence of a dysregulated inflammatory cytokine profile, by examining various circulating biomarkers. Results Our results show that many biomarkers, across TEG, cytokine and lipid groups, were greatly dysregulated in the T2DM sample. Furthermore, our T2DM sample’s coagulation profiles were significantly more hypercoagulable when compared to our heathy sample, and ultrastructural analysis confirmed a matted and denser clot structure in the T2DM sample. Conclusions We suggest that dysregulated circulating molecules may in part be responsible for a hypercoagulable state and vascular dysfunction in the T2DM sample. We propose further that a personalized approach could be of great value when planning treatment and tracking the patient health status after embarking on a treatment regimes, and that looking to novel inflammatory and vascular biomarkers might be crucial. Electronic supplementary material The online version of this article (10.1186/s12933-019-0870-9) contains supplementary material, which is available to authorized users.

Parkinson’s disease (PD) is a well-known neurodegenerative disease with a strong association established with systemic inflammation. Recently, the role of the gingipain protease group from Porphyromonas gingivalis was implicated in Alzheimer’s disease and here we present evidence, using a fluorescent antibody to detect gingipain R1 (RgpA), of its presence in a PD population. To further elucidate the action of this gingipain, as well as the action of the lipopolysaccharide (LPS) from P. gingivalis, low concentrations of recombinant RgpA and LPS were added to purified fluorescent fibrinogen. We also substantiate previous findings regarding PD by emphasizing the presence of systemic inflammation via multiplex cytokine analysis, and demonstrate hypercoagulation using thromboelastography (TEG), confocal and electron microscopy. Biomarker analysis confirmed significantly increased levels of circulating proinflammatory cytokines. In our PD and control blood analysis, our results show increased hypercoagulation, the presence of amyloid formation in plasma, and profound ultrastructural changes to platelets. Our laboratory analysis of purified fibrinogen with added RgpA, and/or LPS, showed preliminary data with regards to the actions of the protease and the bacterial membrane inflammagen on plasma proteins, to better understand the nature of established PD.

Background The reasons for reduced exercise capacity in diabetes mellitus (DM) remains incompletely understood, although diastolic dysfunction and diabetic cardiomyopathy are often favored explanations. However, there is a paucity of literature detailing cardiac function and reserve during incremental exercise to evaluate its significance and contribution. We sought to determine associations between comprehensive measures of cardiac function during exercise and maximal oxygen consumption (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\dot{V}O_{2}$$\end{document}V˙O2peak), with the hypothesis that the reduction in exercise capacity and cardiac function would be associated with co-morbidities and sedentary behavior rather than diabetes itself. Methods This case–control study involved 60 subjects [20 with type 1 DM (T1DM), 20 T2DM, and 10 healthy controls age/sex-matched to each diabetes subtype] performing cardiopulmonary exercise testing and bicycle ergometer echocardiography studies. Measures of biventricular function were assessed during incremental exercise to maximal intensity. Results T2DM subjects were middle-aged (52 ± 11 years) with a mean T2DM diagnosis of 12 ± 7 years and modest glycemic control (HbA1c 57 ± 12 mmol/mol). T1DM participants were younger (35 ± 8 years), with a 19 ± 10 year history of T1DM and suboptimal glycemic control (HbA1c 65 ± 16 mmol/mol). Participants with T2DM were heavier than their controls (body mass index 29.3 ± 3.4 kg/m2 vs. 24.7 ± 2.9, P = 0.001), performed less exercise (10 ± 12 vs. 28 ± 30 MET hours/week, P = 0.031) and had lower exercise capacity (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\dot{V}O_{2}$$\end{document}V˙O2peak = 26 ± 6 vs. 38 ± 8 ml/min/kg, P

OBJECTIVE To determine whether pulmonary microvascular disease is detectable in subjects with diabetes and associated with diminished exercise capacity using a novel echocardiographic marker quantifying the pulmonary transit of agitated contrast bubbles (PTAC). RESEARCH DESIGN AND METHODS Sixty participants (40 with diabetes and 20 control subjects) performed cardiopulmonary (maximal oxygen consumption [VO2peak]) and semisupine bicycle echocardiography exercise tests within a 1-week period. Pulmonary microvascular disease was assessed using PTAC (the number of bubbles traversing the pulmonary circulation to reach the left ventricle, categorized as low PTAC or high PTAC). Echocardiographic measures of cardiac output, pulmonary artery pressures, and biventricular function were obtained during exercise. RESULTS Subjects with diabetes and control subjects were of similar age (44 ± 13 vs. 43 ± 13 years, P = 0.87) and sex composition (70% vs. 65% male, P = 0.7). At peak exercise, low PTAC was present in more participants with diabetes than control subjects (41% vs. 12.5%, χ2 P = 0.041) and, in particular, in more subjects with diabetes with microvascular complications compared with both those without complications and control subjects (55% vs. 26% vs. 13%, χ2 P = 0.02). When compared with high PTAC, low PTAC was associated with a 24% lower VO2peak (P = 0.006), reduced right ventricular function (P = 0.015), and greater pulmonary artery pressures during exercise (P = 0.02). CONCLUSIONS PTAC is reduced in diabetes, particularly in the presence of microvascular pathology in other vascular beds, suggesting that it may be a meaningful indicator of pulmonary microvascular disease with important consequences for cardiovascular function and exercise capacity.

There is unequivocal evidence that exercise results in considerable health benefits. These are the result of positive hormonal, metabolic, neuronal, and structural changes brought about by the intermittent physiological challenge of exercise. However, there is evolving evidence that intense exercise may place disproportionate physiological stress on the right ventricle (RV) and the pulmonary circulation. Both echocardiographic and invasive studies are consistent in demonstrating that pulmonary arterial pressures increase progressively with exercise intensity, such that the harder one exercises, the greater the load on the RV. This disproportionate load can result in fatigue or damage of the RV if the intensity and duration of exercise is sufficiently prolonged. This is distinctly different from the load imposed by exercise on the left ventricle (LV), which is moderated by a greater capacity for reductions in systemic afterload. Finally, given the increasing RV demand during exercise, it may be hypothesized that chronic exercise–induced cardiac remodeling (the so-called athlete’s heart) may also disproportionately affect the RV. Indeed, there is evidence, although somewhat inconsistent, that RV volume increases may be relatively greater than those for the LV. Perhaps more importantly, there is a suggestion that chronic endurance exercise may cause electrical remodeling, predisposing some athletes to serious arrhythmias originating from the RV. Thus, a relatively consistent picture is emerging of acute stress, prolonged fatigue, and long-term remodeling, which all disproportionately affect the RV. Thus, we contend that the RV should be considered a potential Achilles’ heel of the exercising heart.

The aim of this study was to describe maximal fat oxidation (MFO) rates in an athletic population.In total, 1121 athletes (933 males and 188 females), from a variety of sports and competitive level, undertook a graded exercise test on a treadmill in a fasted state (≥5 h fasted). Rates of fat oxidation were determined using indirect calorimetry.The average MFO was 0.59 ± 0.18 g·min, ranging from 0.17 to 1.27 g·min. Maximal rates occurred at an average exercise intensity of 49.3% ± 14.8% V˙O2max, ranging from 22.6% to 88.8% V˙O2max. In absolute terms, male athletes had significantly higher MFO compared with females (0.61 and 0.50 g·min, respectively, P0.001). Expressed relative to fat-free mass (FFM), MFO were higher in the females compared with males (MFO/FFM: 11.0 and 10.0 mg·kg·FFM·min, respectively, P0.001). Soccer players had the highest MFO/FFM (10.8 mg·kg·FFM·min), ranging from 4.1 to 20.5 mg·kg·FFM·min, whereas American Football players displayed the lowest rates of MFO/FFM (9.2 mg·kg·FFM·min). In all athletes, and when separated by sport, large individual variations in MFO rates were observed. Significant positive correlations were found between MFO (g·min) and the following variables: FFM, V˙O2max, FATMAX (the exercise intensity at which the MFO was observed), percent body fat, and duration of fasting. When taken together these variables account for 47% of the variation in MFO.MFO and FATMAX vary significantly between athletes participating in different sports but also in the same sport. Although variance in MFO can be explained to some extent by body composition and fitness status, more than 50% of the variance is not explained by these variables and remains unaccounted for.

Root growth is a highly dynamic process influenced by genetic background and environment. This paper reports the development of R scripts that enable root growth kinematic analysis that complements a new motion analysis tool: PlantVis. Root growth of Arabidopsis thaliana expressing a plasma membrane targeted GFP (C24 and Columbia 35S:LTI6b-EGFP) was imaged using time-lapse confocal laser scanning microscopy. Displacement of individual pixels in the time-lapse sequences was estimated automatically by PlantVis, producing dense motion vector fields. R scripts were developed to extract kinematic growth parameters and report displacement to ± 0.1 pixel. In contrast to other currently available tools, Plantvis-R delivered root velocity profiles without interpolation or averaging across the root surface and also estimated the uncertainty associated with tracking each pixel. The PlantVis-R analysis tool has a range of potential applications in root physiology and gene expression studies, including linking motion to specific cell boundaries and analysis of curvature. The potential for quantifying genotype × environment interactions was examined by applying PlantVis-R in a kinematic analysis of root growth of C24 and Columbia, under contrasting carbon supply. Large genotype-dependent effects of sucrose were recorded. C24 exhibited negligible differences in elongation zone length and elongation rate but doubled the density of lateral roots in the presence of sucrose. Columbia, in contrast, increased its elongation zone length and doubled its elongation rate and the density of lateral roots.

Left ventricular diastolic dysfunction is a well-described complication of systemic hypertension. However, less is known regarding the effect of chronic pressure overload on right ventricular (RV) diastolic function. We hypothesized that pulmonary hypertension (PHT) is associated with abnormal RV early relaxation and that this would be best shown by invasive pressure measurement. Twenty-five patients undergoing right heart catheterization for investigation of breathlessness and/or suspected PHT were studied. In addition to standard measurements, RV pressure was sampled with a high-fidelity micromanometer, and RV pressure/time curves were analyzed. Patients were divided into a PHT group and a non-PHT group on the basis of a derived mean pulmonary artery systolic pressure of 25 mmHg. Eleven patients were classified to the PHT group. This group had significantly higher RV minimum diastolic pressure ([Formula: see text] vs. [Formula: see text] mmHg, [Formula: see text]) and RV end-diastolic pressure (RVEDP; [Formula: see text] vs. [Formula: see text] mmHg, [Formula: see text]), and RV τ was significantly prolonged ([Formula: see text] vs. [Formula: see text] ms, [Formula: see text]). There were strong correlations between RV τ and RV minimum diastolic pressure ([Formula: see text], [Formula: see text]) and between RV τ and RVEDP ([Formula: see text], [Formula: see text]). There was a trend toward increased RV contractility (end-systolic elastance) in the PHT group ([Formula: see text] vs. [Formula: see text] mmHg/mL, [Formula: see text]) and a correlation between RV systolic pressure and first derivative of maximum pressure change ([Formula: see text], [Formula: see text]). Stroke volumes were similar. Invasive measures of RV early relaxation are abnormal in patients with PHT, whereas measured contractility is static or increasing, which suggests that diastolic dysfunction may precede systolic dysfunction. Furthermore, there is a strong association between measures of RV relaxation and RV filling pressures.

Root growth in the field is often slowed by a combination of soil physical stresses, including mechanical impedance, water stress, and oxygen deficiency. The stresses operating may vary continually, depending on the location of the root in the soil profile, the prevailing soil water conditions, and the degree to which the soil has been compacted. The dynamics of root growth responses are considered in this paper, together with the cellular responses that underlie them. Certain root responses facilitate elongation in hard soil, for example, increased sloughing of border cells and exudation from the root cap decreases friction; and thickening of the root relieves stress in front of the root apex and decreases buckling. Whole root systems may also grow preferentially in loose versus dense soil, but this response depends on genotype and the spatial arrangement of loose and compact soil with respect to the main root axes. Decreased root elongation is often accompanied by a decrease in both cell flux and axial cell extension, and recent computer-based models are increasing our understanding of these processes. In the case of mechanical impedance, large changes in cell shape occur, giving rise to shorter fatter cells. There is still uncertainty about many aspects of this response, including the changes in cell walls that control axial versus radial extension, and the degree to which the epidermis, cortex, and stele control root elongation. Optical flow techniques enable tracking of root surfaces with time to yield estimates of two-dimensional velocity fields. It is demonstrated that these techniques can be applied successfully to time-lapse sequences of confocal microscope images of living roots, in order to determine velocity fields and strain rates of groups of cells. In combination with new molecular approaches this provides a promising way of investigating and modelling the mechanisms controlling growth perturbations in response to environmental stresses.

Objectives Pro-inflammatory cytokines have been noted to increase following exercise but their relationship to exercise-induced cardiac dysfunction has not previously been investigated. We sought to evaluate whether exercise-induced cardiac dysfunction was associated with increases in cytokines, particularly the pro-inflammatory cytokines IL-1 beta, IL-12p70 and TNF alpha, which have been most implicated in cardiac pathology. Methods 40 well-trained endurance athletes underwent evaluation prior to and immediately following one of four endurance sporting events ranging from 3 to 11 hours duration. Cytokines (IL-1 beta, IL-6, IL-8, IL-10, IL-12p70 and TNF alpha) were analyzed by flow cytometry from serum samples collected within 50 minutes of race completion. Cardiac troponin (cTnI) and B-type natriuretic peptide were combined with an echocardiographic assessment of cardiac function, and a composite of cTnI > 0.04 mu g/L, BNP increase > 10 ng/L and a decrease in right ventricular ejection (RVEF) > 10% were prospectively defined as evidence of myocardial dysfunction. Results Relative to baseline, IL-6 IL-8 and IL-10 increased 8.5-, 2.9-, and 7.1-fold, respectively, P

It would seem that the “oft forgotten ventricle” can be forgotten no longer. For many decades, we have looked to the left ventricle (LV) as the major determinant of a patient’s cardiac health and prognosis, but a study in this issue of iJACC by Park et al. [(1)][1] reminds us that the right

The performance of various low-level motion estimation methods applied to fluorescence labelled growing cellular structures imaged using confocal laser scanning microscopy is investigated. This is a challenging and unusual domain for motion estimation methods. A selection of methods are discussed that can be contrasted in terms of how much spatial or temporal contextual information is used. The Lucas Kanade feature tracker, a spatially and temporally localised method, was, as one would expect, accurate around resolvable structure. It was not able to track the smaller, repetitive cell structure in the root tip and was somewhat prone to identifying spurious features. This approach is improved by developing a full multi-frame, robust, Bayesian method, and it is demonstrated that by using extra frames with motion constraints reduces such errors. Next, spatially global methods are discussed, including robust variational smoothing and Markov Random Field (MRF) modelling. A key conclusion that is drawn from investigation of these methods is that generic low-level (robust) smoothing functions do not provide good results in this application and that this is probably due to the large regions with little stable structure. Furthermore, contrary to recently reported successes, graph cuts and loopy belief propagation for MAP estimation of the MRF labels provided often poor and inconsistent estimates. The results suggest the need for greater emphasis on temporal smoothing for generic low-level motion estimation tools and more task specific, spatial constraints, perhaps in the form of high level models in order to accurately recover motion from such data. Finally, the form of the estimated growth is briefly discussed and related to contemporary biological models. We hope that this paper will assist non-specialists in applying state-of-the-art methods to this form of data.

Motion estimation from confocal scanning laser microscope images of growing plant cell structures presents interesting challenges; motion exhibits multiple local discontinuities and noise is non-isotropic and non-Gaussian. A method is presented for estimating motion of cell networks based on a physically motivated, part-based model of cell boundary structure. Each part models the shape and appearance of a localised image region and can undergo constrained non-rigid deformation. This enables motion discontinuities between parts to be modelled. Parts are coupled in order to improve localisation and increase computational efficiency. Results from applying MCMC show accurate localisation of the structure across multiple frames. The form of the model assists biologists in interpreting growth.

a Department of Cardiology, Royal Perth Hospital, Perth, Australia b University of Western Australia, School of Medicine and Pharmacology, Perth, Australia c Neurovascular Hypertension & Kidney Disease Laboratory, Baker IDI Heart & Diabetes Institute, Australia d Heart Centre, Alfred Hospital, Melbourne, Australia e Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia