Imaging of Myocardial Fatty Acid Oxidation

Myocardial fuel selection is a key feature of the health and function of the heart, with clear links between myocardial function and fuel selection and important impacts of fuel selection on ischemia tolerance. Radiopharmaceuticals provide uniquely valuable tools for in vivo, non-invasive assessment of these aspects of cardiac function and metabolism. Here we review the landscape of imaging probes developed to provide noninvasive assessment of myocardial fatty acid oxidation (MFAO). Also, we review the state of current knowledge that myocardial fatty acid imaging has helped establish of static and dynamic fuel selection that characterizes cardiac and cardiometabolic disease and the interplay between fuel selection and various aspects of cardiac function

Increasing learners' satisfaction/intention to adopt more e-learning

Purpose: E-learning is an organisationally risky investment given the cost and poor levels of adoption by users. In order to gain a better understanding of this problem, a study was conducted into the use of e-learning in a rail organisation. Design/methodology/approach: Using an online survey, employees of a rail-sector organisation were questioned about their use and likelihood of adoption of e-learning. This study explores the factors that affect the way in which learners experience and perceive such systems. Using statistical analysis, twelve hypotheses are tested and explored. Relationships between learning satisfaction, intention to adopt and the characteristics of e-learning systems were established. Findings: The study found that e-learning characteristics can buffer the relationship between learner characteristics and intention to adopt further e-learning in the future. Further, we found that high levels of support can compensate individuals who are low in technological efficacy to adopt e-learning. Research limitations/implications: The cross-sectional design of the study and its focus on measuring intention to adopt as opposed to actual adoption are both limitations. Future research using longitudinal design and research employing a time lag design measuring actual adoption as well as intention are recommended. Practical implications: From a practical perspective, organizations can focus on the actual content and authenticity of the learning experience delivered by the e-learning system to significantly impact how employees will perceive and use e-learning in the future. Low technological efficacy individuals tend not to adopt new technology. Instead of changing individuals’ personalities, organizations can implement supportive policies and practices which would lead to higher e-learning adoption rate among low efficacy individuals. Originality/value: The study integrates technology adoption and learning literatures in developing enablers for e-learning in organizations. Further, this study collects data from rail employees, and therefore the findings are practical to an industry

Indenyl rhodium N-Heterocyclic carbene complexes for catalytic C-H borylation

Metal-catalysed C-H activation offers the ability to access key synthetic targets in more straightforward reactions than previously used methods. However, undirected activation pathways face issues of selectivity and low rates of reaction that make substituting simple hydrocarbons difficult. Indenyl (Ind) and fluorenyl ligands offer increased reactivity compared to cyclopentadienyl groups, which have been used previously in C-H borylation, and combining these donors with electron-donating NHC ligands was investigated for the borylation of arenes and alkanes. Additionally, the effects of tethered systems were explored to see whether the catalytic ability is enhanced. [Rh(Ind)(SIPr)(C2H4)], [Rh(Ind)(SIPr)(COE)] and [Rh(Ind)(SIPr)(CO)] (SIPr = 1,3- bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene, COE = cis-cyclooctene) were synthesised and characterised by multinuclear NMR spectroscopy and X-ray diffraction. Only the ethylene and cyclooctene complexes were found to be reactive under photolytic conditions and towards silanes. Photolysis led to the loss of coordinated alkenes and the formation of a cyclometallated species due to C-H activation of the NHC substituents. With reducing silanes or hydrogen, a rhodium dihydride complex was observed, that is hypothesised to form via the reaction of the cyclometallated species, while less reducing silanes led to the formation of the oxidative addition product. Both [Rh(Ind)(SIPr)(C2H4)] and [Rh(Ind)(SIPr)(COE)] were found to be catalytically competent for the borylation of benzene, while the carbonyl complex was found to be unreactive under these conditions. Borylation of a selection of arenes showed that the selectivity was comparable to previously reported rhodium catalysts, which is dominated by steric effects, however, the reactivity was lower compared to previously reported catalysts such as [RhCp*(C6Me6)]. Borylation of decane and octane showed that the cyclooctene complex was capable of borylating alkanes, albeit in low yields. Stoichiometric experiments monitored by NMR spectroscopy provided evidence that the catalysis proceeds via rhodium boryl hydride species, with the previously identified cyclometallated species also likely to play a role. The synthesis of fluorenyl-tethered saturated-NHC ligands required the development of homobimetallic synergic bases in order to bring about a ring-opening deprotonation of a spirocyclic intermediate. The structure of [Li2(μ2 ‐Ph){μ2 ‐N(SiMe3)2}] was crystallographically characterised as a coordination polymer, and reaction with the spirocyclic compound led to the formation of dialkali metal complexes of a fluorenidetehered NHC ligand that incorporated a bridging amide group. The use of these bimetallic complexes as ligand transfer reagents gave rhodium carbonyl and ethene complexes in low yields. Initial testing of these complexes in the borylation of benzene found that the carbonyl species was inactive while the ethene complex was less active than the related monodentate species. Overall, this research has demonstrated that NHC ligands can be used to develop Rhcomplexes capable of C-H activation, the oxidative addition of silanes and the catalytic borylation of hydrocarbons. This supports the idea that a [Rh(Ind)(NHC)] fragment (16 electron for η 5 -indenyl, or 14 electron with η 3 -indenyl) can mimic the reactivity of the previously successful [Rh(Cp)(L)] and [Rh(Cp*)] fragments. Although the compounds synthesised in this thesis were not better catalysts than literature examples, they hold much promise because the incorporation of a tuneable NHC ligand on the metal centre can lead to future improvements, especially considering the potential importance of cyclometallated species in C-H activation reactivit

Cardiovascular consequences of metabolic syndrome

The metabolic syndrome (MetS) is defined as the concurrence of obesity-associated cardiovascular risk factors including abdominal obesity, impaired glucose tolerance, hypertriglyceridemia, decreased HDL cholesterol, and/or hypertension. Earlier conceptualizations of the MetS focused on insulin resistance as a core feature, and it is clearly coincident with the above list of features. Each component of the MetS is an independent risk factor for cardiovascular disease and the combination of these risk factors elevates rates and severity of cardiovascular disease, related to a spectrum of cardiovascular conditions including microvascular dysfunction, coronary atherosclerosis and calcification, cardiac dysfunction, myocardial infarction, and heart failure. While advances in understanding the etiology and consequences of this complex disorder have been made, the underlying pathophysiological mechanisms remain incompletely understood, and it is unclear how these concurrent risk factors conspire to produce the variety of obesity-associated adverse cardiovascular diseases. In this review, we highlight current knowledge regarding the pathophysiological consequences of obesity and the MetS on cardiovascular function and disease, including considerations of potential physiological and molecular mechanisms that may contribute to these adverse outcomes

Combination GLP-1 and Insulin Treatment Fails to Alter Myocardial Fuel Selection Versus Insulin Alone in Type 2 Diabetes

Context Glucagon-like peptide-1 (GLP-1) and the clinically available GLP-1 agonists have been shown to exert effects on the heart. It is unclear whether these effects occur at clinically used doses in vivo in humans, possibly contributing to CVD risk reduction. Objective To determine whether liraglutide at clinical dosing augments myocardial glucose uptake alone or in combination with insulin compared to insulin alone in metformin-treated Type 2 diabetes mellitus. Design Comparison of myocardial fuel utilization after 3 months of treatment with insulin detemir, liraglutide, or combination detemir+liraglutide. Setting Academic hospital Participants Type 2 diabetes treated with metformin plus oral agents or basal insulin. Interventions Insulin detemir, liraglutide, or combination added to background metformin Main Outcome Measures Myocardial blood flow, fuel selection and rates of fuel utilization evaluated using positron emission tomography, powered to demonstrate large effects. Results We observed greater myocardial blood flow in the insulin-treated groups (median[25th, 75th percentile]: detemir 0.64[0.50, 0.69], liraglutide 0.52[0.46, 0.58] and detemir+liraglutide 0.75[0.55, 0.77] mL/g/min, p=0.035 comparing 3 groups and p=0.01 comparing detemir groups to liraglutide alone). There were no evident differences between groups in myocardial glucose uptake (detemir 0.040[0.013, 0.049], liraglutide 0.055[0.019, 0.105], detemir+liraglutide 0.037[0.009, 0.046] µmol/g/min, p=0.68 comparing 3 groups). Similarly there were no treatment group differences in measures of myocardial fatty acid uptake or handling, and no differences in total oxidation rate. Conclusions These observations argue against large effects of GLP-1 agonists on myocardial fuel metabolism as mediators of beneficial treatment effects on myocardial function and ischemia protection

Effect of Prolonged Sitting and Breaks in Sitting Time on Endothelial Function

Sitting time (ST) is associated with cardiovascular disease risk factors, whereas breaking ST has been reported to be beneficial for reducing cardiovascular risk. Purpose: The objective of this study is to examine the effects of breaking ST on superficial femoral artery (SFA) endothelial function. Hypotheses: 1) Prolonged sitting would induce endothelial dysfunction and changes in shear forces, and 2) breaking ST with brief periods of activity would prevent attenuation in endothelial function. Methods: Twelve nonobese men (24.2 ± 4.2 yr) participated in two randomized 3-h sitting trials. In the sitting (SIT) trial, subjects were seated on a firmly cushioned chair for 3 h without moving their lower extremities. In the breaking ST trial (ACT), subjects sat similar to the SIT trial but walked on a treadmill for 5 min at 2 mph at 30 min, 1 h 30 min, and 2 h 30 min during the sitting interval. SFA flow-mediated dilation (FMD) was assessed at baseline, 1 h, 2 h, and 3 h in each trial. Statistical analyses were performed using dependent variables SFA FMD and shear rates. Significance was set at P ≤ 0.05. Results: In the SIT trial, there was a significant decline in SFA FMD from baseline to 3 h (baseline, 4.72% ± 3.78%; 1 h, 0.52% ± 0.85%; 2 h, 1.66% ± 1.11%; 3 h, 2.2% ± 2.15; P < 0.05 by ANOVA) accompanied by a decline in mean shear rate and antegrade shear rate but no difference in shear rate (area under the curve). By two-way repeated-measures ANOVA, ACT prevented the sitting-induced decline in FMD (baseline, 4.5% ± 2.3%; 1 h, 5.04% ± 2.85%; 2 h, 5.28% ± 5.05%; 3 h, 6.9% ± 4.5%) along with no decline in shear rates. Conclusion: Three hours of sitting resulted in a significant impairment in shear rate and SFA FMD. When light activity breaks were introduced hourly during sitting, the decline in FMD was prevented

Links Between Optical and X-ray Light in Scorpius X-1

We observed the low-mass X-ray binary Sco X-1 for 12 nights simultaneously using the Rossi X-Ray Timing Explorer and the Otto Struve Telescope at McDonald Observatory at 1 second time resolution. This is among the most comprehensive simultaneous X-Ray/optical data sets of Sco X-1. Evidence of reprocessing was observed in the form of nine positive, near-zero lag peaks in the cross correlation function, eight of which were relatively small and took the shape of piecewise exponential functions. These peaks were initially identified by eye, after which a computational identification scheme was developed to confirm their significance. Based on their short lags (less than 4 seconds), as well as their occurrence on the flaring branch and soft apex, the small cross correlation features are likely to be caused by reprocessing off the outer disc, although the companion could still make a contribution to their tails. The Z track was parameterized using a rank number scheme so that the system's location on the track could be numerically defined. Plotting the results against the optical reveals an increasing step function when moving from the horizontal to the normal to the flaring branch, with differential optical levels at ~0.47, ~0.57, and ~1.1 respectively. An additional correlation between Z track location and the optical was found on the upper flaring branch. An optical intensity histogram reveals a transition region between the normal and flaring branches with only intermediate fluxes.Comment: Accepted for publication in the Monthly Notices of the Royal Astronomical Societ

A rare case of bone marrow infiltration by medulloblastoma in a child.

A seven-year-old boy was previously treated for the primarya posterior fossa tumour, medulloblastoma, with extensive central nervous system metastases including leptomeningeal and intrathecal spinal disease; methylation profiling confirmed a Group 4 tumour. At initial presentation a chemotherapy approach was preferred, due to both his young age and extent of disease; this achieved complete radiological and cytological remission prior to consolidation with high-dose chemotherapy and autologous stem cell rescue. He then experienced an asymptomatic localised posterior fossa relapse on surveillance imaging, treated with complete surgical resection, craniospinal irradiation and maintenance chemotherapy. This chemotherapy was interrupted due to poor count recovery following irradiation, and a bone marrow aspirate and trephine were performed which excluded metastatic medulloblastoma or secondary leukaemia. Alternative maintenance with temozolomide was well tolerated. Unfortunately, end-of-treatment MRI imaging of the neuro-axis revealed an asymptomatic new small enhancing intracranial lesion. An early repeat MRI was performed six weeks later which showed minor progression of the intracranial disease and no intrathecal metastases, but new low T1 signal in multiple vertebral bodies with sparing of T3 and T7 vertebrae (arrows; left image) compared with the imaging performed just six weeks previously. Full blood count revealed Hb 97 g/l, WCC 7.7 x109/l, neutrophils 5.4 x109/l and platelets 204 x109/l. In view of the radiological appearances, bone marrow aspirate and trephine were performed from the posterior iliac crest. Aspirate revealed heavy infiltration with clusters of non-haematopoietic cells, characterized by high nuclear:cytoplasmic ratio, open chromatin and agranular, pale basophilic cytoplasm with vacuolation (right upper image). Trephine immunohistochemistry demonstrated positive staining for synaptophysin, CD56, Neu-N (right lower image), retained INI1 and negative CD99 and desmin, confirming medulloblastoma. Spread of medulloblastoma to the bone marrow is a very rare event. In this case, despite an unremarkable full blood count, radiological changes in the spinal column correlated with easily identified disease in aspirate and trephine samples taken from the posterior iliac crest suggesting widespread marrow infiltration were confirmed by bone marrow examination. Early identification of extracranial metastasis afforded the family and clinicians the opportunity to make informed choices regarding ongoing management

Comparison of β-Cell Function Between Overweight/Obese Adults and Adolescents Across the Spectrum of Glycemia

OBJECTIVE: Type 2 diabetes is a growing health problem among both adults and adolescents. To better understand the differences in the pathogenesis of diabetes between these groups, we examined differences in β-cell function along the spectrum of glucose tolerance. RESEARCH DESIGN AND METHODS: We evaluated 89 adults and 50 adolescents with normal glucose tolerance (NGT), dysglycemia, or type 2 diabetes. Oral glucose tolerance test results were used for C-peptide and insulin/glucose minimal modeling. Model-derived and direct measures of insulin secretion and insulin sensitivity were compared across glycemic stages and between age-groups at each stage. RESULTS: In adolescents with dysglycemia, there was marked insulin resistance (insulin sensitivity index: adolescents, median [interquartile range] 1.8 [1.1-2.4] × 10-4; adults, 5.0 [2.3-9.9]; P = 0.01). The nature of β-cell dysfunction across stages of dysglycemia differed between the groups. We observed higher levels of secretion among adolescents than adults (total insulin secretion: NGT, 143 [103-284] × 10-9/min adolescent vs. 106 [71-127], P = 0.001); adults showed stepwise impairments in static insulin secretion (NGT, 7.5 [4.0-10.3] × 10-9/min; dysglycemia, 5.0 [2.3-9.9]; type 2 diabetes, 0.7 [0.1-2.45]; P = 0.003), whereas adolescents showed diabetes-related impairment in dynamic secretion (NGT, 1,905 [1,630-3,913] × 10-9; dysglycemia, 2,703 [1,323-3,637]; type 2 diabetes, 1,189 [269-1,410]; P = 0.001). CONCLUSIONS: Adults and adolescents differ in the underlying defects leading to dysglycemia, and in the nature of β-cell dysfunction across stages of dysglycemia. These results may suggest different approaches to diabetes prevention in youths versus adults