Morphology of the Leather Defect Light Flecks and Spots

The skin histology and the scanning electron microscope morphology of the hide defect light flecks and spots after tanning were studied in 11 steers infested with biting lice (Damalinia bovis). Nine steers from herds free of lice were used as controls. Skin biopsies from 6 of the animals in the lice infested group showed mild to moderate hyperkeratosis and moderate perivascular to diffuse dermatitis with infiltration of mainly mononuclear cells and some eosinophilic granulocytes. The steers were slaughtered at an age of 18 to 23 months. Light flecks and spots occurred on all examined hides from the infested group after tanning. No examined hides from the control group demonstrated similar damage. Both light microscopic examination of sections of tanned hide with light flecks and spots and scanning electron microscopy of the same defects showed superficial grain loss and craters with a irregular fibre base encircled by smooth and intact grain

Moderate and heavy metabolic stress interval training improve arterial stiffness and heart rate dynamics in humans

Traditional continuous aerobic exercise training attenuates age-related increases of arterial stiffness, however, training studies have not determined whether metabolic stress impacts these favourable effects. Twenty untrained healthy participants (n = 11 heavy metabolic stress interval training, n = 9 moderate metabolic stress interval training) completed 6 weeks of moderate or heavy intensity interval training matched for total work and exercise duration. Carotid artery stiffness, blood pressure contour analysis, and linear and non-linear heart rate variability were assessed before and following training. Overall, carotid arterial stiffness was reduced (p  0.05). This study demonstrates the effectiveness of interval training at improving arterial stiffness and autonomic function, however, the metabolic stress was not a mediator of this effect. In addition, these changes were also independent of improvements in aerobic capacity, which were only induced by training that involved a high metabolic stress

Choice of generic antihypertensive drugs for the primary prevention of cardiovascular disease - A cost-effectiveness analysis

<p>Abstract</p> <p>Background</p> <p>Hypertension is one of the leading causes of cardiovascular disease (CVD). A range of antihypertensive drugs exists, and their prices vary widely mainly due to patent rights. The objective of this study was to explore the cost-effectiveness of different generic antihypertensive drugs as first, second and third choice for primary prevention of cardiovascular disease.</p> <p>Methods</p> <p>We used the Norwegian Cardiovascular Disease model (NorCaD) to simulate the cardiovascular life of patients from hypertension without symptoms until they were all dead or 100 years old. The risk of CVD events and costs were based on recent Norwegian sources.</p> <p>Results</p> <p>In single-drug treatment, all antihypertensives are cost-effective compared to no drug treatment. In the base-case analysis, the first, second and third choice of antihypertensive were calcium channel blocker, thiazide and angiotensin-converting enzyme inhibitor. However the sensitivity and scenario analyses indicated considerable uncertainty in that angiotensin receptor blockers as well as, angiotensin-converting enzyme inhibitors, beta blockers and thiazides could be the most cost-effective antihypertensive drugs.</p> <p>Conclusions</p> <p>Generic antihypertensives are cost-effective in a wide range of risk groups. There is considerable uncertainty, however, regarding which drug is the most cost-effective.</p

Targeting miR-423-5p reverses exercise training–induced HCN4 channel remodeling and sinus bradycardia

Rationale: Downregulation of the pacemaking ion channel, HCN4 (hyperpolarization-activated cyclic nucleotide gated channel 4), and the corresponding ionic current, If, underlies exercise training–induced sinus bradycardia in rodents. If this occurs in humans, it could explain the increased incidence of bradyarrhythmias in veteran athletes, and it will be important to understand the underlying processes. Objective: To test the role of HCN4 in the training-induced bradycardia in human athletes and investigate the role of microRNAs (miRs) in the repression of HCN4. Methods and Results: As in rodents, the intrinsic heart rate was significantly lower in human athletes than in nonathletes, and in all subjects, the rate-lowering effect of the HCN selective blocker, ivabradine, was significantly correlated with the intrinsic heart rate, consistent with HCN repression in athletes. Next-generation sequencing and quantitative real-time reverse transcription polymerase chain reaction showed remodeling of miRs in the sinus node of swim-trained mice. Computational predictions highlighted a prominent role for miR-423-5p. Interaction between miR-423-5p and HCN4 was confirmed by a dose-dependent reduction in HCN4 3′-untranslated region luciferase reporter activity on cotransfection with precursor miR-423-5p (abolished by mutation of predicted recognition elements). Knockdown of miR-423-5p with anti-miR-423-5p reversed training-induced bradycardia via rescue of HCN4 and If. Further experiments showed that in the sinus node of swim-trained mice, upregulation of miR-423-5p (intronic miR) and its host gene, NSRP1, is driven by an upregulation of the transcription factor Nkx2.5. Conclusions: HCN remodeling likely occurs in human athletes, as well as in rodent models. miR-423-5p contributes to training-induced bradycardia by targeting HCN4. This work presents the first evidence of miR control of HCN4 and heart rate. miR-423-5p could be a therapeutic target for pathological sinus node dysfunction in veteran athletes

Heart failure patients demonstrate impaired changes in brachial artery blood flow and shear rate pattern during moderate-intensity cycle exercise

New Findings What is the central question of this study? We explored whether heart failure (HF) patients demonstrate different exercise-induced brachial artery shear rate patterns compared with control subjects. What is the main finding and its importance? Moderate-intensity cycle exercise in HF patients is associated with an attenuated increase in brachial artery anterograde and mean shear rate and skin temperature. Differences between HF patients and control subjects cannot be explained fully by differences in workload. HF patients demonstrate a less favourable shear rate pattern during cycle exercise compared with control subjects. Repeated elevations in shear rate (SR) in conduit arteries, which occur during exercise, represent a key stimulus to improve vascular function. We explored whether heart failure (HF) patients demonstrate distinct changes in SR in response to moderate-intensity cycle exercise compared with healthy control subjects. We examined brachial artery SR during 40 min of cycle exercise at a work rate equivalent to 65% peak oxygen uptake in 14 HF patients (65 ± 7 years old, 13 men and one woman) and 14 control subjects (61 ± 5 years old, 12 men and two women). Brachial artery diameter, SR and oscillatory shear index (OSI) were assessed using ultrasound at baseline and during exercise. The HF patients demonstrated an attenuated increase in mean and anterograde brachial artery SR during exercise compared with control subjects (time × group interaction, P = 0.003 and P 0.05). In conclusion, HF patients demonstrate a less favourable SR pattern during cycle exercise than control subjects, characterized by an attenuated mean and anterograde SR and by increased OSI

Chronic CaMKII inhibition blunts the cardiac contractile response to exercise training

Activation of the multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a critical role modulating cardiac function in both health and disease. Here, we determined the effect of chronic CaMKII inhibition during an exercise training program in healthy mice. CaMKII was inhibited by KN-93 injections. Mice were randomized to the following groups: sham sedentary, sham exercise, KN-93 sedentary, and KN-93 exercise. Cardiorespiratory function was evaluated by ergospirometry during treadmill running, echocardiography, and cardiomyocyte fractional shortening and calcium handling. The results revealed that KN-93 alone had no effect on exercise capacity or fractional shortening. In sham animals, exercise training increased maximal oxygen uptake by 8% (p < 0.05) compared to a 22% (p < 0.05) increase after exercise in KN-93 treated mice (group difference p < 0.01). In contrast, in vivo fractional shortening evaluated by echocardiography improved after exercise in sham animals only: from 25 to 32% (p < 0.02). In inactive mice, KN-93 reduced rates of diastolic cardiomyocyte re-lengthening (by 25%, p < 0.05) as well as Ca2+ transient decay (by 16%, p < 0.05), whereas no such effect was observed after exercise training. KN-93 blunted exercise training response on cardiomyocyte fractional shortening (63% sham vs. 18% KN-93; p < 0.01 and p < 0.05, respectively). These effects could not be solely explained by the Ca2+ transient amplitude, as KN-93 reduced it by 20% (p < 0.05) and response to exercise training was equal (64% sham and 47% KN-93; both p < 0.01). We concluded that chronic CaMKII inhibition increased time to 50% re-lengthening which were recovered by exercise training, but paradoxically led to a greater increase in maximal oxygen uptake compared to sham mice. Thus, the effect of chronic CaMKII inhibition is multifaceted and of a complex nature

Even low level of physical activity is associated with reduced mortality among people with metabolic syndrome, a population based study (the HUNT 2 study, Norway)

<p>Abstract</p> <p>Background</p> <p>Low levels of physical activity may increase the risk of developing metabolic syndrome, a cluster of metabolic factors that are associated with the risk of premature death. It has been suggested that physical activity may reduce the impact of factors associated with metabolic syndrome, but it is not known whether physical activity may reduce mortality in people with metabolic syndrome.</p> <p>Methods</p> <p>In a prospective study of 50,339 people, 13,449 had metabolic syndrome at baseline and were followed up for ten years to assess cause-specific mortality. The population was divided into two age groups: those younger than 65 years of age and those older than age 65. Information on their physical activity levels was collected at baseline.</p> <p>Results</p> <p>Metabolic syndrome was associated with higher mortality from all causes (hazard ratio (HR) 1.35, 95% confidence interval (95% CI) 1.20 to 1.52) and from cardiovascular causes (HR 1.78, 95% CI 1.39 to 2.29) in people younger than 65 years old than among other populations. In older people, there was no overall association of metabolic syndrome with mortality. People with metabolic syndrome who reported high levels of physical activity at baseline were at a reduced risk of death from all causes compared to those who reported no physical activity, both in the younger age group (HR 0.52, 95% CI 0.37 to 0.73) and in the older age group (HR 0.59, 95% CI 0.47 to 0.74).</p> <p>Conclusion</p> <p>Among people with metabolic syndrome, physical activity was associated with reduced mortality from all causes and from cardiovascular causes. Compared to inactivity, even low levels of physical activity were associated with reduced mortality.</p

Novel role for thioredoxin reductase-2 in mitochondrial redox adaptations to obesogenic diet and exercise in heart and skeletal muscle

Increased fatty acid availability and oxidative stress are physiological consequences of exercise (Ex) and a high-fat, high-sugar (HFHS) diet. Despite these similarities, the global effects of Ex are beneficial, whereas HFHS diets are largely deleterious to the cardiovascular system. The reasons for this disparity are multifactorial and incompletely understood. We hypothesized that differences in redox adaptations following HFHS diet in comparison to exercise may underlie this disparity, particularly in mitochondria. Our objective in this study was to determine mechanisms by which heart and skeletal muscle (red gastrocnemius, RG) mitochondria experience differential redox adaptations to 12 weeks of HFHS diet and/or exercise training (Ex) in rats. Surprisingly, both HFHS feeding and Ex led to contrasting effects in heart and RG, in that mitochondrial H2O2 decreased in heart but increased in RG following both HFHS diet and Ex, in comparison to sedentary animals fed a control diet. These differences were determined to be due largely to increased antioxidant/anti-inflammatory enzymes in the heart following the HFHS diet, which did not occur in RG. Specifically, upregulation of mitochondrial thioredoxin reductase-2 occurred with both HFHS and Ex in the heart, but only with Ex in RG, and systematic evaluation of this enzyme revealed that it is critical for suppressing mitochondrial H2O2 during fatty acid oxidation. These findings are novel and important in that they illustrate the unique ability of the heart to adapt to oxidative stress imposed by HFHS diet, in part through upregulation of thioredoxin reductase-2. Furthermore, upregulation of thioredoxin reductase-2 plays a critical role in preserving the mitochondrial redox status in the heart and skeletal muscle with exercise.Funding from the National Institutes of Health, United State

Cost effectiveness of pediatric pneumococcal conjugate vaccines: a comparative assessment of decision-making tools

BACKGROUND: Several decision support tools have been developed to aid policymaking regarding the adoption of pneumococcal conjugate vaccine (PCV) into national pediatric immunization programs. The lack of critical appraisal of these tools makes it difficult for decision makers to understand and choose between them. With the aim to guide policymakers on their optimal use, we compared publicly available decision-making tools in relation to their methods, influential parameters and results. METHODS: The World Health Organization (WHO) requested access to several publicly available cost-effectiveness (CE) tools for PCV from both public and private provenance. All tools were critically assessed according to the WHO's guide for economic evaluations of immunization programs. Key attributes and characteristics were compared and a series of sensitivity analyses was performed to determine the main drivers of the results. The results were compared based on a standardized set of input parameters and assumptions. RESULTS: Three cost-effectiveness modeling tools were provided, including two cohort-based (Pan-American Health Organization (PAHO) ProVac Initiative TriVac, and PneumoADIP) and one population-based model (GlaxoSmithKline's SUPREMES). They all compared the introduction of PCV into national pediatric immunization program with no PCV use. The models were different in terms of model attributes, structure, and data requirement, but captured a similar range of diseases. Herd effects were estimated using different approaches in each model. The main driving parameters were vaccine efficacy against pneumococcal pneumonia, vaccine price, vaccine coverage, serotype coverage and disease burden. With a standardized set of input parameters developed for cohort modeling, TriVac and PneumoADIP produced similar incremental costs and health outcomes, and incremental cost-effectiveness ratios. CONCLUSIONS: Vaccine cost (dose price and number of doses), vaccine efficacy and epidemiology of critical endpoint (for example, incidence of pneumonia, distribution of serotypes causing pneumonia) were influential parameters in the models we compared. Understanding the differences and similarities of such CE tools through regular comparisons could render decision-making processes in different countries more efficient, as well as providing guiding information for further clinical and epidemiological research. A tool comparison exercise using standardized data sets can help model developers to be more transparent about their model structure and assumptions and provide analysts and decision makers with a more in-depth view behind the disease dynamics. Adherence to the WHO guide of economic evaluations of immunization programs may also facilitate this process. Please see related article: http://www.biomedcentral.com/1741-7007/9/55