Stresses in reinforcing rings due to axial forces in cylindrical and conical stressed skins

At the ends of a monocoque fuselage concentrated axial forces in the skin must generally be taken up. Such axial forces must also be taken up in the case of other members where axial forces from the neighboring stressed skin construction must be considered. In order to take up these axial forces two bulkheads or reinforcing frames may be arranged at the positions where the forces are applied. If these bulkheads are in the form of rings, bending moments are set up in them. In the present paper computations are performed for obtaining the value of these bending moments

Absolute quantification of human liver phosphorus-containing metabolites in vivo using an inhomogeneous spoiling magnetic field gradient

Purpose Absolute concentrations of high-energy phosphorus (31P) metabolites in liver provide more important insight into physiologic status of liver disease compared to resonance integral ratios. A simple method for measuring absolute concentrations of 31P metabolites in human liver is described. The approach uses surface spoiling inhomogeneous magnetic field gradi-ent to select signal from liver tissue. The technique avoids issues caused by respiratory motion, chemical shift dispersion associated with linear magnetic field gradients, and increased tissue heat deposition due to radiofrequency absorption, especially at high field strength. Methods Amethod to localize signal from liver was demonstrated using superficial and highly non-uniform magnetic field gradients, which eliminate signal(s) from surface tissue(s) located between the liver and RF coil. A double standard method was implemented to determine absolute 31P metabolite concentrations in vivo. 8 healthy individuals were examined in a 3

Can smartphone wireless ECGs be used to accurately assess ECG intervals in pediatrics? A comparison of mobile health monitoring to standard 12-lead ECG

BACKGROUND:Arrhythmias in children are often paroxysmal, complicating the ability to capture the abnormal rhythm on routine ECG during an outpatient visit. The Alivecor Kardia Mobile (KM) device is a wireless mobile health (mHealth) device that generates a single lead ECG tracing with a FDA-approved algorithm for detection of atrial fibrillation in adults. OBJECTIVE:The goal of this study is to assess the accuracy of interval measurements on KM tracings by directly comparing to standard 12-lead ECGs in pediatric patients. METHODS:This single center, prospective study enrolled pediatric outpatients, age 20ms with 4/9 (44%) having a conduction disorder and 2/9 (22%) having marked sinus arrhythmia. Bland-Altman method of agreement demonstrated strong agreement for QRSd and QTc. The AF algorithm reported 4/30 (13%) false positive "possible AF" diagnoses (rhythm over-read on KM demonstrated n = 3 marked sinus arrhythmia, n = 1 sinus rhythm with aberrated PACs) resulting in a specificity of 87%. CONCLUSION:The Alivecor Kardia device produces accurate single lead ECG tracings in both healthy children and children with cardiac disease or rhythm abnormalities across the pediatric spectrum. This mHealth application provides an accurate, non-invasive, real-time approach for ambulatory ECG monitoring in children and adolescents

In vivo creatine kinase reaction kinetics at rest and stress in type II diabetic rat heart

The effects of type II diabetes on cardiac creatine kinase (CK) enzyme activity and/or flux are unknown. We therefore measured steady‐state phosphocreatine (PCr) and adenosine triphosphate (ATP) content and forward CK reaction kinetic parameters in Zucker Diabetic Fatty (ZDF) rat hearts, a type II diabetes research model. At baseline the PCr to ATP ratio (PCr/ATP) was significantly lower in diabetic heart when compared with matched controls (1.71 ± 0.21 vs. 2.26 ± 0.24, P < 0.01). Furthermore, the forward CK reaction rate constant (k(f)) was higher in diabetic animals (0.52 ± 0.09 s(−1) vs. 0.35 ± 0.06 s(−1), P < 0.01) and CK flux calculated as a product of PCr concentration ([PCr]) and k(f) was similar between two groups (4.32 ± 1.05 μmol/g/s vs. 4.94 ± 1.23 μmol/g/s, P = 0.20). Dobutamine administration resulted in similar increases in heart rate (~38%) and k(f) (~0.12 s(−1)) in both groups. No significant change in PCr and ATP content was observed with dobutamine. In summary, our data showed reduced PCr/ATP in diabetic myocardium as an indicator of cardiac energy deficit. The forward CK reaction rate constant is elevated at baseline which might reflect a compensatory mechanics to support energy flux through the CK shuttle and maintain constant ATP supply. When hearts were stimulated similar increase in k(f) was observed in both groups thus it seems that CK shuttle does not limit ATP supply for the range of workload studied

Complex interplay between the lipin 1 and the hepatocyte nuclear factor 4 alpha (HNF4alpha) pathways to regulate liver lipid metabolism

Lipin 1 is a bifunctional protein that serves as a metabolic enzyme in the triglyceride synthesis pathway and regulates gene expression through direct protein-protein interactions with DNA-bound transcription factors in liver. Herein, we demonstrate that lipin 1 is a target gene of the hepatocyte nuclear factor 4α (HNF4α), which induces lipin 1 gene expression in cooperation with peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) through a nuclear receptor response element in the first intron of the lipin 1 gene. The results of a series of gain-of-function and loss-of-function studies demonstrate that lipin 1 coactivates HNF4α to activate the expression of a variety of genes encoding enzymes involved in fatty acid catabolism. In contrast, lipin 1 reduces the ability of HNF4α to induce the expression of genes encoding apoproteins A4 and C3. Although the ability of lipin to diminish HNF4α activity on these promoters required a direct physical interaction between the two proteins, lipin 1 did not occupy the promoters of the repressed genes and enhances the intrinsic activity of HNF4α in a promoter-independent context. Thus, the induction of lipin 1 by HNF4α may serve as a mechanism to affect promoter selection to direct HNF4α to promoters of genes encoding fatty acid oxidation enzymes

Multiparametric immunoimaging maps inflammatory signatures in murine myocardial infarction models

In the past 2 decades, research on atherosclerotic cardiovascular disease has uncovered inflammation to be a key driver of the pathophysiological process. A pressing need therefore exists to quantitatively and longitudinally probe inflammation, in preclinical models and in cardiovascular disease patients, ideally using non-invasive methods and at multiple levels. Here, we developed and employe

Genomic and metabolic disposition of non-obese Type 2 Diabetic rats to increased myocardial fatty acid metabolism

Lipotoxicity of the heart has been implicated as a leading cause of morbidity in Type 2 Diabetes Mellitus (T2DM). While numerous reports have demonstrated increased myocardial fatty acid (FA) utilization in obese T2DM animal models, this diabetic phenotype has yet to be demonstrated in non-obese animal models of T2DM. Therefore, the present study investigates functional, metabolic, and genomic differences in myocardial FA metabolism in non-obese type 2 diabetic rats. The study utilized Goto-Kakizaki (GK) rats at the age of 24 weeks. Each rat was imaged with small animal positron emission tomography (PET) to estimate myocardial blood flow (MBF) and myocardial FA metabolism. Echocardiograms (ECHOs) were performed to assess cardiac function. Levels of triglycerides (TG) and non-esterified fatty acids (NEFA) were measured in both plasma and cardiac tissues. Finally, expression profiles for 168 genes that have been implicated in diabetes and FA metabolism were measured using quantitative PCR (qPCR) arrays. GK rats exhibited increased NEFA and TG in both plasma and cardiac tissue. Quantitative PET imaging suggests that GK rats have increased FA metabolism. ECHO data indicates that GK rats have a significant increase in left ventricle mass index (LVMI) and decrease in peak early diastolic mitral annular velocity (E’) compared to Wistar rats, suggesting structural remodeling and impaired diastolic function. Of the 84 genes in each the diabetes and FA metabolism arrays, 17 genes in the diabetes array and 41 genes in the FA metabolism array were significantly up-regulated in GK rats. Our data suggest that GK rats’ exhibit increased genomic disposition to FA and TG metabolism independent of obesity

Sexual dimorphism in myocardial acylcarnitine and triglyceride metabolism

Figure S1. Concentrations of non-esterified fatty acid moieties in NOD and Wistar rats by sex. (PPTX 163 kb

The EXERRT Trial: EXErcise to Regadenoson in Recovery Trial : a Phase 3b, Open-label, Parallel Group, Randomized, Multicenter Study to Assess Regadenoson Administration Following an Inadequate Exercise Stress Test as Compared to Regadenoson Without Exercise for Myocardial Perfusion Imaging Using a SPECT Protocol

BACKGROUND: This study assessed the non-inferiority and safety of regadenoson administration during recovery from inadequate exercise compared with administration without exercise. METHODS: Patients unable to achieve adequate exercise stress were randomized to regadenoson 0.4 mg either during recovery (Ex-Reg) or 1 hour after inadequate exercise (Regadenoson) (MPI1). All patients also underwent non-exercise regadenoson MPI 1-14 days later (MPI2). The number of segments with reversible perfusion defects (RPDs) detected using single photon emission computerized tomography imaging was categorized. The primary analysis evaluated the majority agreement rate between Ex-Reg and Regadenoson groups. RESULTS: 1,147 patients were randomized. The lower bound of the 95% confidence interval of the difference in agreement rates (-6%) was above the -7.5% non-inferiority margin, demonstrating non-inferiority of Ex-Reg to Regadenoson. Adverse events were numerically less with Ex-Reg (MPI1). In the Ex-Reg group, one patient developed an acute coronary syndrome and another had a myocardial infarction following regadenoson after exercise. Upon review, both had electrocardiographic changes consistent with ischemia prior to regadenoson. CONCLUSIONS: Administering regadenoson during recovery from inadequate exercise results in comparable categorization of segments with RPDs and with careful monitoring appears to be well tolerated in patients without signs/symptoms of ischemia during exercise and recovery

Resting myocardial perfusion quantification with CMR arterial spin labeling at 1.5 T and 3.0 T

<p>Abstract</p> <p>Background</p> <p>The magnetic resonance technique of arterial spin labeling (ASL) allows myocardial perfusion to be quantified without the use of a contrast agent. This study aimed to use a modified ASL technique and <it>T</it>₁regression algorithm, previously validated in canine models, to calculate myocardial blood flow (MBF) in normal human subjects and to compare the accuracy and repeatability of this calculation at 1.5 T and 3.0 T. A computer simulation was performed and compared with experimental findings.</p> <p>Results</p> <p>Eight subjects were imaged, with scans at 3.0 T showing significantly higher <it>T</it>₁values (<it>P </it>< 0.001) and signal-to-noise ratios (SNR) (<it>P </it>< 0.002) than scans at 1.5 T. The average MBF was found to be 0.990 ± 0.302 mL/g/min at 1.5 T and 1.058 ± 0.187 mL/g/min at 3.0 T. The repeatability at 3.0 T was improved 43% over that at 1.5 T, although no statistically significant difference was found between the two field strengths. In the simulation, the accuracy and the repeatability of the MBF calculations were 61% and 38% higher, respectively, at 3.0 T than at 1.5 T, but no statistically significant differences were observed. There were no significant differences between the myocardial perfusion data sets obtained from the two independent observers. Additionally, there was a trend toward less variation in the perfusion data from the two observers at 3.0 T as compared to 1.5 T.</p> <p>Conclusion</p> <p>This suggests that this ASL technique can be used, preferably at 3.0 T, to quantify myocardial perfusion in humans and with further development could be useful in the clinical setting as an alternative method of perfusion analysis.</p