The acute effects of light on murine sleep during the dark phase: importance of melanopsin for maintenance of light‐induced sleep

Light exerts a direct effect on sleep and wakefulness in nocturnal and diurnal animals, with a light pulse during the dark phase suppressing locomotor activity and promoting sleep in the former. In the present study, we investigated this direct effect of light on various sleep parameters by exposing mice to a broad range of illuminances (0.2–200 μW/cm²; equivalent to 1–1000 lux) for 1 h during the dark phase (zeitgeber time 13–14). Fitting the data with a three‐parameter log model indicated that ～0.1 μW/cm² can generate half the sleep response observed at 200 μW/cm². We observed decreases in total sleep time during the 1 h following the end of the light pulse. Light reduced the latency to sleep from ~30 min in darkness (baseline) to ~10 min at the highest intensity, although this effect was invariant across the light intensities used. We then assessed the role of melanopsin during the rapid transition from wakefulness to sleep at the onset of a light pulse and the maintenance of sleep with a 6‐h 20 μW/cm² light pulse. Even though the melanopsin knockout mice had robust induction of sleep (~35 min) during the first hour of the pulse, it was not maintained. Total sleep decreased by almost 65% by the third hour in comparison with the first hour of the pulse in mice lacking melanopsin, whereas only an 8% decrease was observed in wild‐type mice. Collectively, our findings highlight the selective effects of light on murine sleep, and suggest that melanopsin‐based photoreception is primarily involved in sustaining light‐induced sleep.     

CRIPTO overexpression promotes mesenchymal differentiation in prostate carcinoma cells through parallel regulation of AKT and FGFR activities

Members of the EGF-CFC (Cripto, FRL-1, Cryptic) protein family are increasingly recognized as key mediators of cell movement and cell differentiation during vertebrate embryogenesis. The founding member of this protein family, CRIPTO, is overexpressed in various human carcinomas. Yet, the biological role of CRIPTO in this setting remains unclear. Here, we find CRIPTO expression as especially high in a subgroup of primary prostate carcinomas with poorer outcome, wherein resides cancer cell clones with mesenchymal traits. Experimental studies in PCa models showed that one notable function of CRIPTO expression in prostate carcinoma cells may be to augment PI3K/AKT and FGFR1 signaling, which promotes epithelial-mesenchymal transition and sustains a mesenchymal state. In the observed signaling events, FGFR1 appears to function parallel to AKT, and the two pathways act cooperatively to enhance migratory, invasive and transformation properties specifically in the CRIPTO overexpressing cells. Collectively, these findings suggest a novel molecular network, involving CRIPTO, AKT, and FGFR signaling, in favor of the emergence of mesenchymal-like cancer cells during the development of aggressive prostate tumors.     

Imaging the right heart pulmonary circulation unit: Insights from advanced ultrasound techniques

The right heart pulmonary circulation unit (RH‐PCU) is a key determinant of prognosis in several cardiorespiratory diseases. Although right heart catheterization is considered the gold standard for pulmonary hemodynamic assessment, a comprehensive cardiovascular ultrasound approach is an essential step in the diagnostic–prognostic clinical pathway of patients with suspect or overt pulmonary hypertension. The exponential development of advanced ultrasound techniques (strain, 3‐dimensional echocardiography and lung ultrasound) has led to new insights into the evaluation of RH‐PCU structure and function, overcoming some limitations of standard Doppler echocardiography. In the near future, exercise Doppler echocardiography may become a useful technique for detecting a latent stage of pulmonary hypertension and for evaluating right ventricular contractile reserve.     

Impact of Filling Gas on Subharmonic Emissions of Phospholipid Ultrasound Contrast Agents

Subharmonic signals backscattered from gas-filled lipid-shelled microbubbles have generated significant research interest because they can improve the detection and sensitivity of contrast-enhanced ultrasound imaging. However, the emission of subharmonic signals is strongly characterized by a temporal dependence, the origins of which have not been sufficiently elucidated. The features that influence subharmonic emissions need to be identified not only to better develop next-generation microbubble contrast agents, but also to develop more efficient subharmonic imaging (SHI) modes and therapeutic strategies. We examined the effect of microbubble filling gas on subharmonic emissions. Phospholipid shelled-microbubbles with different gaseous compositions such as sulfur hexafluoride (SF₆), octafluoropropane (C₃F₈) or decafluorobutane (C₄F₁₀), nitrogen (N₂)/C₄F₁₀ or air were insonated using a driving frequency of 10 MHz and peak negative pressure of 450 kPa, and their acoustic responses were tracked by monitoring both second harmonic and subharmonic emissions. Microbubbles were first acoustically characterized with their original gas and then re-characterized after substitution of the original gas with air, SF₆ or C₄F₁₀. A measureable change in intensity of the subharmonic emissions with a 20- to 40-min delayed onset and increasing subharmonic emissions of the order 12–18 dB was recorded for microbubbles filled with C₄F₁₀. Substitution of C₄F₁₀ with air eliminated the earlier observed delay in subharmonic emissions. Significantly, substitution of SF₆ for C₄F₁₀ successfully triggered a delay in the subharmonic emissions of the resultant agents, whereas substitution of C₄F₁₀ for SF₆ eliminated the earlier observed suppression of subharmonic emissions, clearly suggesting that the type of filling gas contained in the microbubble agent influences subharmonic emissions in a time-dependent manner. Because our agents were dispersed in air-stabilized phosphate-buffered saline, these results suggest that the diffusivity of the gas from the agent to the surrounding medium is correlated with the time-dependent evolution of subharmonic emissions.     

Hybrid Interventional Procedures in Congenital Heart Disease

The evolution of congenital cardiac surgery has seen significant innovative advances in collaborative efforts between congenital cardiac surgeons and interventionalists to provide the least invasive intervention with the greatest hemodynamic benefit for patients with congenital heart disease. This review looks at how this collaborative approach has evolved and is being applied to treat a number of congenital conditions across the age ranges.