Objective: The present in vitro study was designed to ascertain whether the presence of sinuses of Valsalva in the aortic root were able to regulate the valve effective orifice area and modulate the gradient across the valve independently from root compliance. Methods: Four different root configurations were prepared. Of the 4, 2 were silicon configurations with the same compliance, 1 with and 1 without sinuses of Valsalva, in which a 25-mm Solo stentless aortic valve was sutured inside. The other 2 configurations were obtained by substituting the upper part of the root with a straight Dacron graft or with a Valsalva graft in a remodeling fashion to reproduce the surgical situation. All roots were mounted in a pulse duplicator to measure the pressure decrease across the valve and effective orifice area at different cardiac outputs. Results: With increasing cardiac output up to 7 L/min, an increase in the pressure decrease across the valve was evident in both configurations without sinuses of Valsalva (7.90 AE 1.7 and 11 mm Hg AE 0.1 mm Hg, respectively) but not in those with sinuses (2.87 AE 0.5 and 2.42 mm Hg AE 0.5 mm Hg). Similarly, with increasing cardiac output, the effective orifice area increased significantly only in the roots with sinuses (5.13 AE 0.5 and 5.47 AE 0.5 vs 3.06 AE 0.3 and 2.50 cm 2 AE 0.02 cm 2 , respectively). Conclusions: When the cardiac output is increased to greater than the resting physiologic values, the presence of sinuses of Valsalva, independently of root compliance, prevents an increase in the pressure decrease across the valve by way of an increase of the effective orifice area.

Although it is well known that antiretroviral drugs (ARVs) across the placenta in different extents, few data are available concerning the impact of the transplacental passage of ARVs on newborn outcome. The aim of this study is to evaluate the transplacental diffusion of ARVs and the clinical assessment of the newborn. Mother and cord lopinavir, nelfinavir, atazanavir and nevirapine plasma levels were determined by high-performance liquid chromatography. Newborn gestational age, weight, and Apgar score were recorded. Cord-to-mother ratio (C:M) was calculated to estimate the placental passage of ARVs. Preterm birth was defined as delivery at <37 weeks of gestation and low birth weight was defined as a birth weight of <2500g. Twenty-six HIV-infected pregnant women were enrolled. Nevirapine presented the highest C:M ratio (0.60 +/- 0.19), the C:M ratio of nelfinavir and atazanavir was 0.37 +/- 0.38 and 0.20 +/- 0.14, respectively. The lopinavir level in the cord was undetectable. The observed prevalence rate of neonatal low birth weight and preterm delivery was 19,2% (n = 5) and 15.4% (n = 4), respectively. A significant linear regression analysis was reported between the C:M ratio and newborn birth weight (p = 0.01). Although the role of highly active antiretroviral therapy (HAART) in preventing mother-to-child transmission is indisputable, these data indicate a pharmacological rationale to the association between birth weight and highly active antiretroviral therapy during pregnancy.

The study was partly funded with research grants from the University of Catania. None of the authors have any conflicting interests to declare.

In the past two decades, relevant advances have been made in the generation of engineered cardiac constructs to be used as functional in vitro models for cardiac research or drug testing, and with the ultimate but still challenging goal of repairing the damaged myocardium. To support cardiac tissue generation and maturation in vitro , the application of biomimetic physical stimuli within dedicated bioreactors is crucial. In particular, cardiac-like mechanical stimulation has been demonstrated to promote development and maturation of cardiac tissue models. Here, we developed an automated bioreactor platform for tunable cyclic stretch and in situ monitoring of the mechanical response of in vitro engineered cardiac tissues. To demonstrate the bioreactor platform performance and to investigate the effects of cyclic stretch on construct maturation and contractility, we developed 3D annular cardiac tissue models based on neonatal rat cardiac cells embedded in fibrin hydrogel. The constructs were statically pre-cultured for 5 days and then exposed to 4 days of uniaxial cyclic stretch (sinusoidal waveform, 10% strain, 1 Hz) within the bioreactor. Explanatory biological tests showed that cyclic stretch promoted cardiomyocyte alignment, maintenance, and maturation, with enhanced expression of typical mature cardiac markers compared to static controls. Moreover, in situ monitoring showed increasing passive force of the constructs along the dynamic culture. Finally, only the stretched constructs were responsive to external electrical pacing with synchronous and regular contractile activity, further confirming that cyclic stretching was instrumental for their functional maturation. This study shows that the proposed bioreactor platform is a reliable device for cyclic stretch culture and in situ monitoring of the passive mechanical response of the cultured constructs. The innovative feature of acquiring passive force measurements in situ and along the culture allows monitoring the construct maturation trend without interrupting the culture, making the proposed device a powerful tool for in vitro investigation and ultimately production of functional engineered cardiac constructs.