Securities Regulation: Shareholder Derivative Actions Against Insiders Under Rule 10b-5

After a general examination of Rule 10b-5 in the context of its traditional application, this comment focuses on the recent developments concerning the rule\u27s function as a weapon for the enforcement of controlling insiders\u27 duties to their corporation

A multi-pulse ultrasound technique for imaging of thick-shelled microbubbles demonstrated in vitro and in vivo

Contrast enhanced ultrasound is a powerful diagnostic tool and ultrasound contrast media are based on microbubbles (MBs). The use of MBs in drug delivery applications and molecular imaging is a relatively new field of research which has gained significant interest during the last decade. MBs available for clinical use are fragile with short circulation half-lives due to the use of a thin encapsulating shell for stabilization of the gas core. Thick-shelled MBs can have improved circulation half-lives, incorporate larger amounts of drugs for enhanced drug delivery or facilitate targeting for use in molecular ultrasound imaging. However, methods for robust imaging of thick-shelled MBs are currently not available. We propose a simple multi-pulse imaging technique which is able to visualize thick-shelled polymeric MBs with a superior contrast-to-tissue ratio (CTR) compared to commercially available harmonic techniques. The method is implemented on a high-end ultrasound scanner and in-vitro imaging in a tissue mimicking flow phantom results in a CTR of up to 23 dB. A proof-of-concept study of molecular ultrasound imaging in a soft tissue inflammation model in rabbit is then presented where the new imaging technique showed an enhanced accumulation of targeted MBs in the inflamed tissue region compared to non-targeted MBs and a mean CTR of 13.3 dB for stationary MBs. The presence of fluorescently labelled MBs was verified by confocal microscopy imaging of tissue sections post-mortem.publishedVersio

Assessment of myocardium at risk with contrast enhanced steady-state free precession cine cardiovascular magnetic resonance compared to single-photon emission computed tomography

<p>Abstract</p> <p>Background</p> <p>Final infarct size following coronary occlusion is determined by the duration of ischemia, the size of myocardium at risk (MaR) and reperfusion injury. The reference method for determining MaR, single-photon emission computed tomography (SPECT) before reperfusion, is impractical in an acute setting. The aim of the present study was to evaluate whether MaR can be determined from the contrast enhanced myocardium using steady-state free precession (SSFP) cine cardiovascular magnetic resonance (CMR) performed one week after the acute event in ST-elevation myocardial infarction (STEMI) patients with total coronary occlusion.</p> <p>Results</p> <p>Sixteen patients with STEMI (age 64 ± 8 years) received intravenous 99 m-Tc immediately before primary percutaneous coronary intervention. SPECT was performed within four hours. MaR was defined as the non-perfused myocardial volume derived with SPECT. CMR was performed 7.8 ± 1.2 days after the myocardial infarction using a protocol in which the contrast agent was administered before acquisition of short-axis SSFP cines. MaR was evaluated as the contrast enhanced myocardial volume in the cines by two blinded observers. MaR determined from the enhanced region on cine CMR correlated significantly with that derived with SPECT (r²= 0.78, p < 0.001). The difference in MaR determined by CMR and SPECT was 0.5 ± 5.1% (mean ± SD). The interobserver variability of contrast enhanced cine SSFP measurements was 1.6 ± 3.7% (mean ± SD) of the left ventricle wall volume.</p> <p>Conclusions</p> <p>Contrast enhanced SSFP cine CMR performed one week after acute infarction accurately depicts MaR prior to reperfusion in STEMI patients with total occlusion undergoing primary PCI. This suggests that a single CMR examination might be performed for determination of MaR and infarct size.</p

Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle

SummaryDNA methylation is a covalent biochemical modification controlling chromatin structure and gene expression. Exercise elicits gene expression changes that trigger structural and metabolic adaptations in skeletal muscle. We determined whether DNA methylation plays a role in exercise-induced gene expression. Whole genome methylation was decreased in skeletal muscle biopsies obtained from healthy sedentary men and women after acute exercise. Exercise induced a dose-dependent expression of PGC-1α, PDK4, and PPAR-δ, together with a marked hypomethylation on each respective promoter. Similarly, promoter methylation of PGC-1α, PDK4, and PPAR-δ was markedly decreased in mouse soleus muscles 45 min after ex vivo contraction. In L6 myotubes, caffeine exposure induced gene hypomethylation in parallel with an increase in the respective mRNA content. Collectively, our results provide evidence that acute gene activation is associated with a dynamic change in DNA methylation in skeletal muscle and suggest that DNA hypomethylation is an early event in contraction-induced gene activation

Afternoon exercise is more efficacious than morning exercise at improving blood glucose levels in individuals with type 2 diabetes : a randomised crossover trial

Data availability The data analysed during the current study are available from the corresponding author on reasonable request. Funding The authors are supported by grants from Novo Nordisk Foundation (NNF14OC0011493 and NNF14OC0009941), Swedish Diabetes Foundation (DIA2015-052), Wenner-Gren Foundation, Swedish Research Council (2015-00165), Strategic Research Program in Diabetes at Karolinska Institutet (2009-1068), Stockholm County Council (SLL20150517 and SLL20170159) and Swedish Heart Lung Foundation (20150423).Peer reviewedPublisher PD