Vertical and Horizontal Transmission of Cell Fusing Agent Virus in Aedes aegypti.

Cell fusing agent virus (CFAV) is an insect-specific flavivirus (ISF) found in Aedes aegypti mosquitoes. ISFs have demonstrated the ability to modulate the infection or transmission of arboviruses such as dengue, West Nile, and Zika viruses. It is thought that vertical transmission is the main route for ISF maintenance in nature. This has been observed with CFAV, but there is evidence of horizontal and venereal transmission in other ISFs. Understanding the route of transmission can inform strategies to spread ISFs to vector populations as a method of controlling pathogenic arboviruses. We crossed individually reared male and female mosquitoes from both a naturally occurring CFAV-positive Ae. aegypti colony and its negative counterpart to provide information on maternal, paternal, and horizontal transmission. RT-PCR was used to detect CFAV in individual female pupal exuviae and was 89% sensitive, but only 42% in male pupal exuviae. This is a possible way to screen individuals for infection without destroying the adults. Female-to-male horizontal transmission was not observed during this study. However, there was a 31% transmission rate from mating pairs of CFAV-positive males to negative female mosquitoes. Maternal vertical transmission was observed with a filial infection rate of 93%. The rate of paternal transmission was 85% when the female remained negative, 61% when the female acquired CFAV horizontally, and 76% overall. Maternal and paternal transmission of CFAV could allow the introduction of this virus into wild Ae. aegypti populations through male or female mosquito releases, and thus provides a potential strategy for ISF-derived arbovirus control. IMPORTANCE Insect-specific flaviviruses (ISFs), are a group of nonpathogenic flaviviruses that only infect insects. ISFs can have a high prevalence in mosquito populations, but their transmission routes are not well understood. The results of this study confirm maternal transmission of cell fusing agent virus (CFAV) and demonstrate that paternal transmission is also highly efficient. Horizontal transmission of CFAV was also observed, aided by evaluation of the pupal infection status before mating with an infected individual. This technique of detecting infection in discarded pupae exuviae has not been evaluated previously and will be a useful tool for others in the field of studying viral transmission in mosquitoes. Identifying these routes of transmission provides information about how CFAV could be maintained in wild populations of mosquitoes and can aid future studies focusing on interactions of CFAV with their hosts and other viruses that infect mosquitoes.

Left ventricular function and geometry in fetuses with severe tricuspid regurgitation.

OBJECTIVE: Neonatal congenital tricuspid valve (TV) dysplasia and/or displacement (Ebstein's malformation) with severe tricuspid regurgitation (TR) is a challenging condition in which outcomes are frequently poor. Little is known about left ventricular (LV) function during the perinatal period in patients with congenital TV disease. The objective of this study was to evaluate LV function in fetuses with congenital TV anomalies associated with significant TR. METHODS: Serial fetal echocardiograms in 16 fetuses with congenital TV dysplasia and/or displacement (five neonatal survivors and 11 fetal or neonatal deaths) were reviewed. LV stroke volume, LV end-diastolic volume (LVEDV), LV end-diastolic dimension (LVIDd), the LV eccentricity index, thoracic and cardiac areas and the cardiothoracic area ratio (CTAR), the right atrium area index, and LV longitudinal strains were compared according to gestational age and clinical outcome. RESULTS: The gestational age-adjusted LVEDV (Z-score) was lower in late gestation (-1.2 ± 1.2 at last examination ≥ 28 weeks) than earlier in gestation (0.3 ± 1.5 at last examination < 28 weeks) and LV output was lower than reported late-gestation normal values. LV short-axis dimension correlated with LV volume and CTAR. LV mid-septal strain was lower than the normal average of fetal mid-septal strain and correlated with the LV eccentricity index. Among these parameters, only the LV eccentricity index differed between survivors and non-survivors. CONCLUSION: LV function and anatomy are abnormal in fetuses with severe congenital TV anomalies and may be important contributors to outcome.

Changes in left heart hemodynamics after technically successful in-utero aortic valvuloplasty.

OBJECTIVE: Severe aortic stenosis in the mid-gestation fetus can progress to hypoplastic left heart syndrome (HLHS). @ In-utero aortic valvuloplasty is an innovative therapy to promote left ventricular growth and function and potentially to prevent HLHS. This study evaluated the effects of mid-gestation fetal balloon aortic valvuloplasty on subsequent fetal left ventricular function and left heart Doppler characteristics. METHODS: We reviewed fetuses with aortic stenosis that underwent attempted in-utero aortic valvuloplasty between 2000 and 2006. Pre-intervention and the latest post-intervention fetal echocardiograms were analyzed to characterize changes in left heart function and Doppler characteristics in utero. RESULTS: Forty-two fetuses underwent attempted aortic valvuloplasty during the study period, 12 of which were excluded from analysis secondary to inadequate follow-up data, termination or fetal demise. Study fetuses (n = 30) underwent pre-intervention echocardiography at a median gestational age of 23 weeks, and were followed for a median of 66 +/- 23 days post-intervention. In 26 fetuses, aortic valvuloplasty was technically successful. Among these 26, left heart physiology was abnormal pre-intervention and improved or normalized after intervention in most cases: biphasic mitral inflow was present in 5/25 (20%) cases pre-intervention and in 21/23 (91%) post-intervention (P < 0.001); moderate or severe mitral regurgitation was present in 14/26 (54%) cases pre-intervention and in 5/23 (22%) post-intervention (P = 0.02); bidirectional flow across the patent foramen ovale was present in 0/26 cases pre-intervention and in 6/25 (24%) post-intervention (P = 0.01); antegrade flow in the transverse arch was present in 0/25 cases pre-intervention and in 17/26 (65%) post-intervention (P < 0.001). The left ventricular ejection fraction increased from 19 +/- 10% pre-intervention to 39 +/- 14% post-intervention (P < 0.001). These changes were not observed in control fetuses (n = 18). CONCLUSION: Fetal aortic valvuloplasty, when technically successful, improves left ventricular systolic function and left heart Doppler characteristics.

A new quantitative method for the diagnosis of right ventricular hypertensive disorders in 3 dimensions.

UNLABELLED: A new 3-dimensional (3D) method is described for the diagnosis of normal and hypertensive right ventricular (RV) conditions on the basis of similarity of RV structure to models of normal average shape or hypertensive average shape. Right ventricular quantification in multiple views (coronal, sagittal, and transverse) was obtained by measuring tangent angle differences (TADs) between RV tracings and average shapes at 128 points around the ventricular contour in each view. The TAD measurements of all views were then combined to quantify the closest 3D fit of the ventricle to a normal or hypertensive model. RESULTS: In 24 lamb casts measured in vitro, an accurate diagnosis was obtained in 11 of 12 normotensive casts (specificity 92%) and 11 of 12 hypertensive casts (sensitivity 92%). CONCLUSION: Accurate 3D diagnosis of in vitro normotensive and hypertensive RV conditions can be realized by measuring the TADs between the ventricle and average-shaped models.

The influence of semicircular canal morphology on endolymph flow dynamics. An anatomically descriptive mathematical model.

The classic Steinhausen/Groen mathematical description of endolymph flow in a toroidal semicircular canal is extended to the case where the size, shape, and curvature of the canal lumen change continuously through the duct, utricle, and ampulla. The resulting second-order differential equation has three coefficients, unlike the equation of a torsion pendulum, which has only two. The salient anatomical parameters which determine endolymph motion are: the length of the central streamline occupying the center of the canal lumen; the area enclosed by this streamline as projected into the plane of rotation; the average inverse cross-sectional area of the lumen (taken around the central streamline); and the average inverse squared cross-sectional area, weighted by a local wall shape factor. These parameters are evaluated and the average displacement of the face of the cupula is estimated for the human, guinea pig, and rat, based on new anatomical data presented in companion papers. The model predicts that the dynamic range of human average cupula motion lies between 520 A and 10 microns.