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Right ventricular (RV) function is the predominant determinant of survival in patients with pulmonary arterial hypertension (PAH). In preclinical models, pharmacological activation of BMP (bone morphogenetic protein) signaling with FK506 (tacrolimus) improved RV function by decreasing RV afterload. FK506 therapy further stabilized three patients with end-stage PAH. Whether FK506 has direct effects on the pressure-overloaded right ventricle is yet unknown. We hypothesized that increasing cardiac BMP signaling with FK506 improves RV structure and function in a model of fixed RV afterload after pulmonary artery banding (PAB). Direct cardiac effects of FK506 on the microvasculature and RV fibrosis were studied after surgical PAB in wild-type and heterozygous Bmpr2 mutant mice. RV function and strain were assessed longitudinally via cardiac magnetic resonance imaging during continuous FK506 infusion. Genetic lineage tracing of endothelial cells (ECs) was performed to assess the contribution of ECs to fibrosis. Molecular mechanistic studies were performed in human cardiac fibroblasts and ECs. In mice, low BMP signaling in the right ventricle exaggerated PAB-induced RV fibrosis. FK506 therapy restored cardiac BMP signaling, reduced RV fibrosis in a BMP-dependent manner independent from its immunosuppressive effect, preserved RV capillarization, and improved RV function and strain over the time course of disease. Endothelial mesenchymal transition was a rare event and did not significantly contribute to cardiac fibrosis after PAB. Mechanistically, FK506 required ALK1 in human cardiac fibroblasts as a BMPR2 co-receptor to reduce TGFβ1-induced proliferation and collagen production. Our study demonstrates that increasing cardiac BMP signaling with FK506 improves RV structure and function independent from its previously described beneficial effects on pulmonary vascular remodeling.

Introduction Due to the disproportionate impact of COVID-19 on communities of color, racial disparities in maternal mortality and morbidity are likely to increase. However, neighborhood and social support factors have yet to be discussed as potential mechanisms by which COVID-19 can exacerbate racial disparities. Methods We examined literature on the role of neighborhood factors and social support on maternal health outcomes and provided analytical perspective on the potential impacts of COVID-19 on Black birthing people. Results Even prior to the pandemic, Black individuals were disproportionately impacted by psychosocial stress. However, the compounding effect of pre-existing and current pandemic psychosocial stressors may be a mechanism by which racial disparities are exacerbated and result in higher rates of maternal mortality and morbidity in Black women. Conclusion We recommend continued monitoring of data related to racial disparities in maternal mortality and morbidity throughout the pandemic. Given that Black women may be disproportionately impacted by psychosocial stress, it is necessary for leadership structures and communities to recognize the potential for worsening disparities and intervene.

BACKGROUND: The COVID-19 pandemic is creating ventilator shortages in many countries that is sparking a conversation about placing multiple patients on a single ventilator. However, on March 26, 2020, six leading medical organizations released a joint statement warning clinicians that attempting this technique could lead to poor outcomes and high mortality. Nevertheless, hospitals around the United States and abroad are considering this technique out of desperation (eg, New York), but there is little data to guide their approach. The overall objective of this study is to utilize a computational model of mechanically ventilated lungs to assess how patient-specific lung mechanics and ventilator settings impact lung tidal volume (VT). METHODS: We developed a lumped-parameter computational model of multiple patients connected to a shared ventilator and validated it against a similar experimental study. We used this model to evaluate how patient-specific lung compliance and resistance would impact VT under 4 ventilator settings of pressure control level, PEEP, breathing frequency, and inspiratory:expiratory ratio. RESULTS: Our computational model predicts VT within 10% of experimental measurements. Using this model to perform a parametric study, we provide proof-of-concept for an algorithm to better match patients in different hypothetical scenarios of a single ventilator shared by > 1 patient. CONCLUSIONS: Assigning patients to preset ventilators based on their required level of support on the lower PEEP/higher F IO 2 scale of the National Institute of Health’s National Heart, Lung, and Blood Institute ARDS Clinical Network (ARDSNet), secondary to lung mechanics, could be used to overcome some of the legitimate concerns of placing multiple patients on a single ventilator. We emphasize that our results are currently based on a computational model that has not been validated against any preclinical or clinical data. Therefore, clinicians considering this approach should not look to our study as an exact estimate of predicted patient VT values.

Pulmonary hypertension (PH) is a progressive disease that is characterized by a gradual increase in both resistive and reactive pulmonary arterial (PA) impedance. Previous studies in a rodent model of PH have shown that reducing the hemodynamic load in the left lung (by banding the left PA) reverses this remodeling phenomenon. However, banding a single side of the pulmonary circulation is not a viable clinical option, so-using in silico modeling–we evaluated if the banding effect can be recreated by replacing the proximal vasculature with a compliant synthetic PA. We developed a computational model of the pulmonary circulation by combining a one-dimensional model of the proximal vasculature with a zero-dimensional line transmission model to the 12th generation. Using this model, we performed four simulations: (1) Control; (2) PH; (3) PH with a stenosis in the left PA; and (4) PH with proximal vessel compliance returned to Control levels. Simulations revealed that vascular changes associated with PH result in an increase in pulse pressure (PP), maximum pressure (Pmax), maximum wall shear stress (WSS), and maximum circumferential stress (σθθ) relative to controls, in the distal circulation. Banding the left PA reduced these measurements of hemodynamic stress in the left lung, but increases them in the right lung. Furthermore, left PA banding increased reactive PA impedance. However, returning the proximal PA compliance to Control levels simultaneously decreased all measures of hemodynamic stress in both lungs, and returned reactive PA impedance to normal levels. In conclusion, if future in vivo studies support the idea of hemodynamic unloading as an effective therapy for PH, this can be surgically achieved by replacing the proximal PA with a compliant prosthesis, and it will have the added benefit of reducing reactive right ventricular afterload.

AimsVentricular–vascular coupling, the ratio between the right ventricle’s contractile state (Ees) and its afterload (Ea), may be a useful metric in the management of paediatric pulmonary arterial hypertension (PAH). In this study we assess the prognostic capacity of the ventricular–vascular coupling ratio (Ees/Ea) derived using right ventricular (RV) pressure alone in children with PAH.MethodsOne hundred and thirty paediatric patients who were diagnosed with PAH via right heart catheterisation were retrospectively reviewed over a 10-year period. Maximum RV isovolumic pressure and end-systolic pressure were estimated using two single-beat methods from Takeuchi et al (Ees/Ea_(Takeuchi)) and from Kind et al (Ees/Ea_(Kind)) and used with an estimate of end-systolic pressure to compute ventricular–vascular coupling from pressure alone. Patients were identified as either idiopathic/hereditary PAH or associated PAH (IPAH/HPAH and APAH, respectively). Haemodynamic data, clinical functional class and clinical worsening outcomes—separated into soft (mild) and hard (severe) event categories—were assessed. Adverse soft events included functional class worsening, syncopal event, hospitalisation due to a proportional hazard-related event and haemoptysis. Hard events included death, transplantation, initiation of prostanoid therapy and hospitalisation for atrial septostomy and Pott’s shunt. Cox proportional hazard modelling was used to assess whether Ees/Ea was predictive of time-to-event.ResultsIn patients with IPAH/HPAH, Ees/Ea_(Kind) and Ees/Ea_(Takeuchi) were both independently associated with time to hard event (p=0.003 and p=0.001, respectively) and when adjusted for indexed pulmonary vascular resistance (p=0.032 and p=0.013, respectively). Neither Ees/Ea_(Kind) nor Ees/Ea_(Takeuchi) were associated with time to soft event. In patients with APAH, neither Ees/Ea_(Kind) nor Ees/Ea_(Takeuchi) were associated with time to hard event or soft event.ConclusionsEes/Ea derived from pressure alone is a strong independent predictor of adverse outcome and could be a potential powerful prognostic tool for paediatric PAH.

Aims The temporal sequence of events underlying functional right ventricular (RV) recovery after improvement of pulmonary hypertension-associated pressure overload is unknown. We sought to establish a novel mouse model of gradual RV recovery from pressure overload and use it to delineate RV reverse-remodelling events. Methods and results Surgical pulmonary artery banding (PAB) around a 26-G needle induced RV dysfunction with increased RV pressures, reduced exercise capacity and caused liver congestion, hypertrophic, fibrotic, and vascular myocardial remodelling within 5 weeks of chronic RV pressure overload in mice. Gradual reduction of the afterload burden through PA band absorption (de-PAB)—after RV dysfunction and structural remodelling were established—initiated recovery of RV function (cardiac output and exercise capacity) along with rapid normalization in RV hypertrophy (RV/left ventricular + S and cardiomyocyte area) and RV pressures (right ventricular systolic pressure). RV fibrotic (collagen, elastic fibres, and vimentin+ fibroblasts) and vascular (capillary density) remodelling were equally reversible; however, reversal occurred at a later timepoint after de-PAB, when RV function was already completely restored. Microarray gene expression (ClariomS, Thermo Fisher Scientific, Waltham, MA, USA) along with gene ontology analyses in RV tissues revealed growth factors, immune modulators, and apoptosis mediators as major cellular components underlying functional RV recovery. Conclusion We established a novel gradual de-PAB mouse model and used it to demonstrate that established pulmonary hypertension-associated RV dysfunction is fully reversible. Mechanistically, we link functional RV improvement to hypertrophic normalization that precedes fibrotic and vascular reverse-remodelling events.

Background: In pulmonary arterial hypertension (PAH), right ventricular (RV) failure is the main cause of mortality. Non-invasive estimation of ventricular-vascular coupling ratio (VVCR), describing contractile response to afterload, could be a valuable tool for monitoring clinical course in children with PAH. This study aimed to test two hypotheses: VVCR by cardiac magnetic resonance (VVCRCMR) correlates with conventional VVCR by right heart catheterization (VVCRRHC) and both correlate with disease severity.Methods and results: Twenty-seven patients diagnosed with idiopathic and associated PAH without post-tricuspid shunt, who underwent RHC and CMR within 17 days at two specialized centers for pediatric PAH were retrospectively studied. Clinical functional status and hemodynamic data were collected. Median age at time of MRI was 14.3 years (IQR: 11.1-16.8), median PVRi 7.6 WU x m(2) (IQR: 4.1-12.2), median mPAP 40 mm Hg (IQR: 28-55) and median WHO-FC 2 (IQR: 2-3). VVCRCMR, defined as stroke volume/end-systolic volume ratio was compared to VVCRRHC by single-beat pressure method using correlation and Bland-Altman plots. VVCRCMR and VVCRRHC showed a strong correlation (r = 0.83, p Conclusions: Non-invasively measured VVCRCMR is feasible in pediatric PAH and comparable to invasively assessed VVCRRHC. Both correlate with functional and hemodynamic measures of disease severity. The role of VVCR assessed by CMR and RHC in clinical decision-making and follow-up in pediatric PAH warrants further clinical investigation. (C) 2019 Elsevier B.V. All rights reserved.

Despite different developmental and pathological processes affecting lung vascular remodeling in both patient populations, differences in 4D MRI findings between children and adults with PAH have not been studied. The purpose of this study was to compare flow hemodynamic state, including flow-mediated shear forces, between pediatric and adult patients with PAH matched by severity of pulmonary vascular resistance index (PVRi). Adults ( n = 10) and children ( n = 10) with PAH matched by pulmonary vascular resistance index (PVRi) and healthy adult ( n = 10) and pediatric ( n = 10) subjects underwent comprehensive 4D-flow MRI to assess peak systolic wall shear stress (WSSmax) measured in the main (MPA), right (RPA), and left pulmonary arteries (LPA), viscous energy loss (EL) along the MPA-RPA and MPA-LPA tract, and qualitative analysis of secondary flow hemodynamics. WSSmax was decreased in all pulmonary vessels in children with PAH when compared with the same age group (all P < 0.05). Similarly, WSSmax was decreased in all pulmonary vessels in adult PAH patients when compared with healthy adult subjects (all P < 0.01). Average EL was increased in adult patients with PAH when compared with the same age group along both MPA-RPA ( P = 0.020) and MPA-LPA ( P = 0.025) tracts. There were no differences in EL indices between adults and pediatric patients. Children and adult patients with PAH have decreased shear hemodynamic forces. However, pathological flow hemodynamic formations appear to be more consistent in adult patients, whereas flow hemodynamic abnormalities appear to be more variable in children with PAH for comparable severity of PVRi. NEW & NOTEWORTHY Both children and adult patients with PAH have decreased shear hemodynamic forces inside the pulmonary arteries associated with the degree of vessel dilation and stiffness. These differences also exist between healthy normotensive children and adults. However, pathological flow hemodynamic formations appear to more uniform in adult patients, whereas in children with PAH flow, hemodynamic abnormalities appear to be more variable. Pathological flow formations appear not to have a major effect on viscous energy loss associated with the flow conduction through proximal pulmonary arteries.

Background The role of interventricular mechanics in pediatric pulmonary arterial hypertension (PAH) and its relation to right ventricular (RV) dysfunction has been largely overlooked. Here, we characterize the impact of maintained pressure overload in the RV–pulmonary artery (PA) axis on myocardial strain and left ventricular (LV) mechanics in pediatric PAH patients in comparison to a preclinical PA-banding (PAB) mouse model. We hypothesize that the PAB mouse model mimics important aspects of interventricular mechanics of pediatric PAH and may be beneficial as a surrogate model for some longitudinal and interventional studies not possible in children. Methods Balanced steady-state free precession (bSSFP) cardiovascular magnetic resonance (CMR) images of 18 PAH and 17 healthy (control) pediatric subjects were retrospectively analyzed using CMR feature-tracking (FT) software to compute measurements of myocardial strain. Furthermore, myocardial tagged-CMR images were also analyzed for each subject using harmonic phase flow analysis to derive LV torsion rate. Within 48 h of CMR, PAH patients underwent right heart catheterization (RHC) for measurement of PA/RV pressures, and to compute RV end-systolic elastance (RV_Ees, a measure of load-independent contractility). Surgical PAB was performed on mice to induce RV pressure overload and myocardial remodeling. bSSFP-CMR, tagged CMR, and intra-cardiac catheterization were performed on 12 PAB and 9 control mice (Sham) 7 weeks after surgery with identical post-processing as in the aforementioned patient studies. RV_Ees was assessed via the single beat method. Results LV torsion rate was significantly reduced under hypertensive conditions in both PAB mice (p = 0.004) and pediatric PAH patients (p es in PAB (r = 0.91, p = 0.05) and PAH subjects (r = 0.51, p = 0.04). In order to compare combined metrics of LV torsion rate and strain parameters principal component analysis (PCA) was used. PCA revealed grouping of PAH patients with PAB mice and control subjects with Sham mice. Similar to LV torsion rate, LV global peak circumferential, radial, and longitudinal strain were significantly (p Conclusions The PAB mouse model resembles PAH-associated myocardial mechanics and may provide a potential model to study mechanisms of RV/LV interdependency.

Background Pulmonary arterial hypertension (PAH) manifests with progressive right ventricular (RV) dysfunction, which eventually impairs the left ventricular function. We hypothesized that 4‐dimensional–flow magnetic resonance imaging can detect flow hemodynamic changes associated with efficient intracardiac flow during noninvasive inhaled nitric oxide (iNO) challenge in children with PAH. Methods and Results Children with PAH (n=10) underwent 2 same‐day separate iNO challenge tests using: (1) 4‐dimensional–flow magnetic resonance imaging and (2) standard catheterization hemodynamics. Intracardiac flow was evaluated using the particle tracking 4‐flow component analysis technique evaluating the direct flow , retained inflow , delayed ejection flow , and residual volume . Respective flow hemodynamic changes were compared with the corresponding catheterization iNO challenge results. The RV analysis revealed decreased direct flow in patients with PAH when compared with controls ( P P P =0.004) and increased proportion of the residual volume ( P =0.014). There was an increase in the RV direct flow during iNO delivery ( P =0.009), with parallel decrease in the residual volume ( P =0.008). Conclusions Children with PAH have abnormal biventricular flow associated with impaired diastolic filling. The flow efficiency is significantly improved in the RV on iNO administration with no change in the left ventricle. The changes in the RV flow have occurred despite the minimal change in catheterization hemodynamics, suggesting that flow hemodynamic evaluation might provide more quantitative insights into vasoreactivity testing in PAH.

Background The clinical mitigation of intracranial hypertension due to traumatic brain injury requires timely knowledge of intracranial pressure to avoid secondary injury or death. Noninvasive intracranial pressure (nICP) estimation that operates sufficiently fast at multihour timescales and requires only common patient measurements is a desirable tool for clinical decision support and improving traumatic brain injury patient outcomes. However, existing model-based nICP estimation methods may be too slow or require data that are not easily obtained. Objective This work considers short- and real-time nICP estimation at multihour timescales based on arterial blood pressure (ABP) to better inform the ongoing development of practical models with commonly available data. Methods We assess and analyze the effects of two distinct pathways of model development, either by increasing physiological integration using a simple pressure estimation model, or by increasing physiological fidelity using a more complex model. Comparison of the model approaches is performed using a set of quantitative model validation criteria over hour-scale times applied to model nICP estimates in relation to observed ICP. Results The simple fully coupled estimation scheme based on windowed regression outperforms a more complex nICP model with prescribed intracranial inflow when pulsatile ABP inflow conditions are provided. We also show that the simple estimation data requirements can be reduced to 1-minute averaged ABP summary data under generic waveform representation. Conclusions Stronger performance of the simple bidirectional model indicates that feedback between the systemic vascular network and nICP estimation scheme is crucial for modeling over long intervals. However, simple model reduction to ABP-only dependence limits its utility in cases involving other brain injuries such as ischemic stroke and subarachnoid hemorrhage. Additional methodologies and considerations needed to overcome these limitations are illustrated and discussed.

Ziel: In diesem Film beschreiben wir unsere Technik der roboter-assistierten radikalen en bloc Zystektomie und Nephroureterektomie mit anschließender Harnableitung bei Patienten mit muskelinvasivem Urothelkarzinom der Harnblase und simultanem Urothelkarzinom der oberen Harnwege oder funktionsloser[zum vollständigen Text gelangen Sie über die oben angegebene URL], 46. Gemeinsame Tagung der Bayerischen Urologenvereinigung und der Österreichischen Gesellschaft für Urologie und Andrologie

In einem 15-minütigen Vortrag wird der Einsatz der Dualen Konsole des Da Vinci Xi Systems an der Urologie des Landesklinikums Wiener Neustadt dargestellt. Beginnend mit einem Überblick über die Möglichkeiten die eine Duale Konsole mit sich bringt, wird im Weiteren das Ausbildungskonzept[zum vollständigen Text gelangen Sie über die oben angegebene URL], 46. Gemeinsame Tagung der Bayerischen Urologenvereinigung und der Österreichischen Gesellschaft für Urologie und Andrologie

Pulmonary hypertension (PH) results in right ventricular (RV) pressure overload and eventual failure. Current research efforts have focused on the RV while overlooking the left ventricle (LV), which is responsible for mechanically assisting the RV during contraction. The objective of this study is to evaluate the biomechanical and gene expression changes occurring in the LV due to RV pressure overload in a mouse model. Nine male mice were divided into two groups: (a) pulmonary arterial banding (PAB, N = 4) and (b) sham surgery (Sham, N = 5). Tagged and steady‐state free precision cardiac MRI was performed on each mouse at 1, 4, and 7 weeks after surgery. At/week7, the mice were euthanized following right/left heart catheterization with RV/LV tissue harvested for histology and gene expression (using RT‐PCR) studies. Compared to Sham mice, the PAB group revealed a significantly decreased LV and RV ejection fraction, and LV maximum torsion and torsion rate, within the first week after banding. In the PAB group, there was also a slight but significant increase in LV perivascular fibrosis, which suggests elevated myocardial stress. LV fibrosis was also accompanied with changes in gene expression in the hypertensive group, which was correlated with LV contractile mechanics. In fact, principal component (PC) analysis of LV gene expression effectively separated Sham and PAB mice along PC2. Changes in LV contractile mechanics were also significantly correlated with unfavorable changes in RV contractile mechanics, but a direct causal relationship was not established. In conclusion, a purely biomechanical insult of RV pressure overload resulted in biomechanical and transcriptional changes in both the RV and LV. Given that the RV relies on the LV for contractile energy assistance, considering the LV could provide prognostic and therapeutic targets for treating RV failure in PH., Right ventricular (RV) failure is a common endpoint in pulmonary hypertension. While most clinical and research efforts are focused on the RV, our research shows that the left ventricle undergoes bio‐mechanical and gene‐expression changes in response to RV pressure overload.

The COVID-19 pandemic is creating ventilator shortages in many countries that is sparking a conversation about placing multiple people on a single ventilator. However, on March 26th the American College of Chest Physicians (CHEST), along with other leading medical organizations, released a joint statement warning clinicians that attempting this technique could lead to poor outcomes and high mortality. Nevertheless, several hospitals around the United States and abroad are turning to this technique out of desperation (e.g. New York), but little data exists to guide their approach. The overall objective of this study is to utilize a computational model of mechanically ventilated lungs to assess how patient-specific lung mechanics and ventilator settings impact lung tidal volume (Vt).MethodsWe developed a single compartment computational model of four patients connected to a shared ventilator and validated it against a similar experimental study. We used this model to evaluate how patient-specific lung compliance (C) and resistance (R) would impact Vt under 5 ventilator settings of pre-set PIP, PEEP, and I:E ratio (suggested by Farkas, J.D. MD as an approach by hospitals to manage multiple patients on a single ventilator).ResultsOur computational model predicts Vt within 10% of experimental measurements. Using this model to perform a parametric study, we provide proof-of-concept for an algorithm to better match patients in different hypothetical scenarios of a single ventilator shared by more than one patient.ConclusionsAssigning patients to pre-set ventilators based on their lung mechanics could be used to overcome some of the legitimate concerns of placing multiple patients on a single ventilator. We emphasize that our results are currently based on a computational model that has not been validated against any pre-clinical/clinical data. Therefore, clinicians considering this approach should not look to our study as an exact estimate of predicted patient tidal volumes.

Pulmonary hypertension may arise as a complication of chronic lung disease typically associated with tissue hypoxia, as well as infectious agents or injury eliciting a type 2 immune response. The onset of pulmonary hypertension in this setting (classified as Group 3) often complicates treatment and worsens prognosis of chronic lung disease. Chronic lung diseases such as chronic obstructive lung disease (COPD), emphysema, and interstitial lung fibrosis impair airflow and alter lung elastance in addition to affecting pulmonary vascular hemodynamics that may culminate in right ventricle dysfunction. To date, functional endpoints in murine models of chronic lung disease have typically been limited to separately measuring airway and lung parenchyma physiology. These approaches may be lengthy and require a large number of animals per experiment. Here, we provide a detailed protocol for combined assessment of airway physiology with cardiovascular hemodynamics in mice. Ultimately, a comprehensive overview of pulmonary function in murine models of injury and disease will facilitate the integration of studies of the airway and vascular biology necessary to understand underlying pathophysiology of Group 3 pulmonary hypertension.

The right ventricle and left ventricle are physically coupled through the interventricular septum. Therefore, changes in the geometry and mechanics of one ventricle can directly affect the function of the other. In treatment of pediatric pulmonary arterial hypertension, the left ventricle is often overlooked, with clinical focus primarily on improving right ventricular function. Pediatric pulmonary arterial hypertension represents a disease distinct from adult pulmonary arterial hypertension based on etiology and survival rates. We aimed to assess left ventricular torsion rate in pediatric pulmonary arterial hypertension and its role in right ventricular dysfunction. Cardiac magnetic resonance images with tissue tagging were prospectively acquired for 18 pediatric pulmonary arterial hypertension (WHO class I) patients and 17 control subjects with no known cardiopulmonary disease. The pulmonary arterial hypertension cohort underwent cardiac magnetic resonance within 48 hours of clinically indicated right heart catheterization. Using right heart catheterization data, we computed single beat estimation of right ventricular end-systolic elastance (as a measure of right ventricular contractility) and ventricular vascular coupling ratio (end-systolic elastance/arterial afterload). Left ventricular torsion rate was quantified from harmonic phase analysis of tagged cardiac magnetic resonance images. Ventricular and pulmonary pressures and pulmonary vascular resistance were derived from right heart catheterization data. Right ventricular ejection fraction and interventricular septum curvature were derived from cardiac magnetic resonance. Left ventricular torsion rate was significantly reduced in pulmonary arterial hypertension patients compared to control subjects (1.40 ± 0.61° vs. 3.02 ± 1.47°, P

Objective Central aortic stiffness and chronic obstructive pulmonary disease (COPD) are associated with increased incidence of devastating aortopathies. However, the exact mechanism leading to elevated aortic stiffness in patients with COPD is unknown. The purpose of this study was to quantify flow and shear hemodynamic indices, known markers of vascular remodeling, in the thoracic aorta of patients with mild to moderate COPD (n = 16) and to compare these results with an age-matched control group (n = 10). Methods Four-dimensional flow magnetic resonance imaging has been applied to measure hemodynamic wall shear stress (WSS) at four specific planes along the ascending aorta, aortic arch, and proximal descending aorta for all subjects. Peak systolic WSS and time-averaged WSS, which respectively reflect magnitude and temporal shear variability, were calculated at standardized planes. Aortic deformation was measured by means of relative area change (RAC) at the midlevel of the ascending and descending aorta. Results Compared with controls, patients with COPD had significantly reduced RAC in the mid ascending aorta (9% vs 18%; P P = .0206). Peak systolic WSS in COPD patients was significantly reduced in all considered planes, with the most dramatic difference occurring in the descending aorta (0.46 vs 0.86 N/m 2 ; P Conclusions Reduced flow shear metrics assessed at specific aortic regions correlated with RAC, a marker of aortic stiffness. Reduced hemodynamic WSS may then contribute to central aortic stiffening and perpetuate the risk for development of severe aortopathy.

This article presents an analysis of literature data of the study of exogenous and endogenous etiologic risk factors for the progression of urolithiasis in elderly and senile patients, the clinical course, modern treatment methods and tactics for managing patients of this age group. It was noted that patients of the older age group require special attention both in the choice of treatment tactics and in further observation due to a decrease in the functional reserves of the renal parenchyma and the presence of concomitant diseases. In the diagnosis and treatment of urolithiasis in elderly patients are preferred to use non-invasive methods. (For citation: Agenosov MP, Kagan OF, Kheyfets VKh. Peculiarities of clinical course of urolithiasis in patients of elderly and senile age. Urologicheskie vedomosti. 2017;7(4):53-59. doi: 10.17816/uroved7453-59).

AIMS: To investigate the possibility that vorticity assessed by four-dimensional flow cardiac magnetic resonance (4D-Flow CMR) in the left ventricle of patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) is a potential marker of early LV diastolic dysfunction (LVDD) and more sensitive than standard echocardiography, and whether changes in vorticity are associated with quantitative computed tomography (CT) and clinical markers of COPD, and right ventricular (RV) echocardiographic markers indicative of ventricular interdependency. METHODS AND RESULTS: Sixteen COPD patients with presumptive LVDD and 10 controls underwent same-day 4D-Flow CMR and Doppler echocardiography to quantify early and late diastolic vorticity as well as standard evaluation for LVDD. Furthermore, all patients underwent detailed CT analysis for COPD markers including percent emphysema and air trapping. The 4D-Flow CMR derived diastolic vorticity measures were correlated with CT measures, standard clinical and CMR markers, and echocardiographic diastolic RV metrics. Early diastolic vorticity was significantly reduced in COPD patients (P

Ziel: In diesem Film beschreiben wir unsere Technik der roboter-assistierten radikalen Zystektomie mit intrakorporaler Harnableitung mit Verwendung des „EndoWrist Staplers“ für das daVinci Xi System bei Patienten mit muskelinvasivem Urothelkarzinom der Harnblase. Methoden: Alle[zum vollständigen Text gelangen Sie über die oben angegebene URL], 45. Gemeinsame Tagung der Österreichischen Gesellschaft für Urologie und Andrologie und der Bayerischen Urologenvereinigung

Pulmonary hypertension (PH) is a degenerative disease characterized by progressively increased right ventricular (RV) afterload that leads to ultimate functional decline. Recent observational studies have documented a decrease in left ventricular (LV) torsion during ejection, with preserved LV ejection fraction (EF) in pediatric and adult PH patients. The objective of this study was to develop a computational model of the biventricular heart and use it to evaluate changes in LV torsion mechanics in response to mechanical, structural, and hemodynamic changes in the RV free wall. The heart model revealed that LV torsion and apical rotation were decreased when increasing RV mechanical rigidity and during re-orientation of RV myocardial fibers, both of which have been demonstrated in PH. Furthermore, structural changes to the RV appear to have a notable impact on RV EF, but little influence on LV EF. Finally, RV pressure overload exponentially increased LV myocardial stress. The computational results found in this study are consistent with clinical observations in adult and pediatric PH patients, which reveal a decrease in LV torsion with preserved LV EF. Furthermore, discovered causes of decreased LV torsion are consistent with RV structural adaptations seen in PH rodent studies, which might also explain suspected stress-induced changes in LV myocardial gene and protein expression.

Objective To evaluate a multicentre series of robot-assisted partial nephrectomy (RAPN) performed for the treatment of large angiomyolipomas (AMLs). Patients and methods Between 2005 and 2016, 40 patients with large or symptomatic AMLs underwent RAPN at five academic centres in the USA. Patient demographics, AML characteristics, operative and postoperative clinical outcomes were recorded and analysed. Surgical outcomes were compared between patients who underwent selective arterial embolisation (SAE) before RAPN and patients who did not undergo pre-RAPN SAE. Results The median (interquartile range [IQR]) tumour diameter was 7.2 (5-8.5) cm, and the median (IQR) nephrometry score was 9 (7-10). Six patients (15%) had a history of tuberous sclerosis and 11 (28%) had previously undergone SAE. The median (IQR) operative time and warm ischaemia time was 207 (180-231) and 22.5 (16-28) min, respectively. A non-clamping technique was used in eight (20%) patients. The median (IQR) estimated blood loss was 200 (100-245) mL, and four patients (10%) received blood transfusion postoperatively. One intraoperative complication occurred (2.5%), and seven postoperative complications occurred in six patients (15%). During a median (IQR) follow-up of 8 (1-15) months, none of the patients developed AML-related symptoms. The median estimated glomerular filtration rate preservation rate was 95%. There were no differences in operative or perioperative outcomes between patients who underwent SAE before RAPN and those who did not. Conclusions Robot-assisted partial nephrectomy appears to be a safe primary or secondary (post-SAE) treatment for large AMLs, with a favourable perioperative morbidity profile and excellent functional preservation. Longer follow-up is required to fully evaluate therapeutic efficacy.

Purpose To develop an estimate of pulmonary vascular resistance (PVR) using blood flow measurements from 3D velocity-encoded phase contract magnetic resonance imaging (here termed 4D MRI). Materials and Methods In all, 17 patients with pulmonary hypertension (PH) and five controls underwent right heart catheterization (RHC), 4D and 2D Cine MRI (1.5T) within 24 hours. MRI was used to compute maximum spatial peak systolic vorticity in the main pulmonary artery (MPA) and right pulmonary artery (RPA), cardiac output, and relative area change in the MPA. These parameters were combined in a four-parameter multivariate linear regression model to arrive at an estimate of PVR. Agreement between model predicted and measured PVR was also evaluated using Bland–Altman plots. Finally, model accuracy was tested by randomly withholding a patient from regression analysis and using them to validate the multivariate equation. Results A decrease in vorticity in the MPA and RPA were correlated with an increase in PVR (MPA: R2 = 0.54, P < 0.05; RPA: R2 = 0.75, P < 0.05). Expanding on this finding, we identified a multivariate regression equation that accurately estimates PVR (R2 = 0.94, P < 0.05) across severe PH and normotensive populations. Bland–Altman plots showed 95% of the differences between predicted and measured PVR to lie within 1.49 Wood units. Model accuracy testing revealed a prediction error of ∼20%. Conclusion A multivariate model that includes MPA relative area change and flow characteristics, measured using 4D and 2D Cine MRI, offers a promising technique for noninvasively estimating PVR in PH patients. J. MAGN. RESON. IMAGING 2016;44:914–922.

A drop of lipid lateral self-diffusion coefficient at the liquid-gel phase transition in lipid membranes is calculated. So far this drop was missing theoretical description. Our microscopic model captures so-called subdiffusion regime, which takes place on 1 ps--100 ns timescale and reveals a jump of self-diffusion coefficient. Calculation of the jump is based on our recent study of liquid-gel phase transition. Subdiffusive regime is described within the free volume theory. Calculated values of self-diffusion coefficient are in agreement with quasielastic neutron scattering measurements. Self-diffusion coefficient is found to be composed of two factors: one is related to an area per lipid change at the phase transition, and the other one is due to an order of magnitude change in the stiffness of entropic repulsive potential.

Computational fluid dynamics (CFD) modeling of the pulmonary vasculature has the potential to reveal continuum metrics associated with the hemodynamic stress acting on the vascular endothelium. It is widely accepted that the endothelium responds to flow-induced stress by releasing vasoactive substances that can dilate and constrict blood vessels locally. The objectives of this study are to examine the extent of patient specificity required to obtain a significant association of CFD output metrics and clinical measures in models of the pulmonary arterial circulation, and to evaluate the potential correlation of wall shear stress (WSS) with established metrics indicative of right ventricular (RV) afterload in pulmonary hypertension (PH). Right heart catheterization (RHC) hemodynamic data and contrast-enhanced computed tomography (CT) imaging were retrospectively acquired for 10 PH patients and processed to simulate blood flow in the pulmonary arteries. While conducting CFD modeling of the reconstructed patient-specific vasculatures, we experimented with three different outflow boundary conditions to investigate the potential for using computationally derived spatially averaged wall shear Stress (SAWSS) as a metric of RV afterload. SAWSS was correlated with both pulmonary vascular resistance (PVR) (R2 = 0.77, P < 0.05) and arterial compliance (C) (R2 = 0.63, P < 0.05), but the extent of the correlation was affected by the degree of patient specificity incorporated in the fluid flow boundary conditions. We found that decreasing the distal PVR alters the flow distribution and changes the local velocity profile in the distal vessels, thereby increasing the local WSS. Nevertheless, implementing generic outflow boundary conditions still resulted in statistically significant SAWSS correlations with respect to both metrics of RV afterload, suggesting that the CFD model could be executed without the need for complex outflow boundary conditions that require invasively obtained patient-specific data. A preliminary study investigating the relationship between outlet diameter and flow distribution in the pulmonary tree offers a potential computationally inexpensive alternative to pressure based outflow boundary conditions.

Pulmonary hypertension (PH) is a devastating disease affecting approximately 15-50 people per million, with a higher incidence in women. PH mortality is mostly attributed to right ventricle (RV) failure, which results from RV hypotrophy due to an overburdened hydraulic workload. The objective of this study is to correlate wall shear stress (WSS) with hemodynamic metrics that are generally accepted as clinical indicators of RV workload and are well correlated with disease outcome. Retrospective right heart catheterization data for 20 PH patients were analyzed to derive pulmonary vascular resistance (PVR), arterial compliance (C), and an index of wave reflections (Γ). Patient-specific contrast-enhanced computed tomography chest images were used to reconstruct the individual pulmonary arterial trees up to the seventh generation. Computational fluid dynamics analyses simulating blood flow at peak systole were conducted for each vascular model to calculate WSS distributions on the endothelial surface of the pulmonary arteries. WSS was found to be decreased proportionally with elevated PVR and reduced C. Spatially averaged WSS (SAWSS) was positively correlated with PVR (R (2) = 0.66), C (R (2) = 0.73), and Γ (R (2) = 0.5) and also showed promising preliminary correlations with RV geometric characteristics. Evaluating WSS at random cross sections in the proximal vasculature (main, right, and left pulmonary arteries), the type of data that can be acquired from phase-contrast magnetic resonance imaging, did not reveal the same correlations. In conclusion, we found that WSS has the potential to be a viable and clinically useful noninvasive metric of PH disease progression and RV health. Future work should be focused on evaluating whether SAWSS has prognostic value in the management of PH and whether it can be used as a rapid reactivity assessment tool, which would aid in selection of appropriate therapies.

Multiple modalities exist for training urologic surgeons in robotic surgery. These include dry and wet lab exercises, virtual reality and augmented reality simulators and animal and cadaver models. The learning curve associated with various robotic surgical procedures is variable, and training curricula aim to help novice surgeons most effectively overcome the steep part of the curve. While a standardized training protocol or credentialing process does not currently exist, multiple innovative training curricula have been developed with the intent of creating a comprehensive and effective learning environment in which to master the skills necessary for performing robotic procedures, and are explored in this chapter.

Background Qualitative and quantitative flow hemodynamic indexes have been shown to reflect right ventricular ( RV ) afterload and function in pulmonary hypertension ( PH ). We aimed to quantify flow hemodynamic formations in pulmonary arteries using 4‐dimensional flow cardiac magnetic resonance imaging and the spatial velocity derivatives helicity and vorticity in a heterogeneous PH population. Methods and Results Patients with PH (n=35) and controls (n=10) underwent 4‐dimensional flow magnetic resonance imaging study for computation of helicity and vorticity in the main pulmonary artery ( MPA ), the right pulmonary artery, and the RV outflow tract. Helicity and vorticity were correlated with standard RV volumetric and functional indexes along with MPA stiffness assessed by measuring relative area change. Patients with PH had a significantly decreased helicity in the MPA (8 versus 32 m/s 2 ; P 2 ; P RV outflow tract– MPA unit (15 versus 42 m/s 2 ; P P P RV ejection fraction (0.865; P P P =0.0008), and relative area change measured at the MPA (0.789; P Conclusions The flow hemodynamic character in patients with PH assessed via quantitative analysis is considerably different when compared with healthy and normotensive controls. A strong association between helicity in pulmonary arteries and ventricular‐vascular coupling suggests a relationship between the mechanical and flow hemodynamic domains.

We sought to compare pulmonary flow hemodynamic indices obtained by Fick and thermodilution catheterization techniques with phase-contrast MRI (PC-MRI) in children with diverse etiologies of pulmonary arterial hypertension (PAH). Calculation of pulmonary flow ( $${\dot{\text{Q}}}_{\text{p}}$$ ) using the Fick principle in most catheter laboratories relies on an estimate of oxygen consumption which may limit its reliability. Flow hemodynamic indices acquired from thirty patients with PAH who underwent successful same-day PC-MRI and catheterization were evaluated for absolute and percent bias. Comparison of $${\dot{\text{Q}}}_{\text{p}}$$ between PC-MRI and Fick revealed poor agreement with an absolute bias of 0.96 ± 0.53 L/min/m2 and percent bias of 27.7 ± 19.6%. Same analysis between PC-MRI and thermodilution revealed better agreement as demonstrated by absolute bias 0.64 ± 0.47 L/min/m2 and percent bias 16.8 ± 12.3%. Retrospectively calculated $${\dot{\text{V}}}_{{{\text{O}}_{2} }}$$ from PC-MRI and LaFarge equations revealed poor agreement, with an absolute bias of 33.4 ± 21.6 mL/min/m2 and percent bias of 25.8 ± 12.6%. We found that Fick-derived flow hemodynamics dramatically differs from PC-MRI computed metrics in children with PAH. The non-invasive nature of PC-MRI and short acquisition time is ideal for pediatric flow evaluation and may offer a novel route of absolute flow and resistance assessment when combined with cardiac catheterization.

Introduction and Objective: The folate receptor (FR) protein is upregulated in numerous epithelial malignancies while having limited expression on normal tissues. This overexpression of FR in renal-cell carcinoma (RCC) can be exploited by attaching nearly any therapeutic or imaging agent for delivery to cancer cells. In one of its first applications, platinum-resistant ovarian cancer, folate was used to deliver pegylated liposomal doxorubicin (a folate-linked vinca alkaloid) and improved progression-free survival versus standard treatment. RCCs are thought to be the second highest FR-expressing cancer. OTL-38 is a folate analogue conjugated with a fluorescent dye that emits light in the near infrared spectrum. This longer wavelength allows for deeper penetration of the fluorescent light through tissues with the potential to better image tumors beneath adipose tissue or deeper into organ parenchyma. We are currently conducting a pilot, phase 2, nonrandomized study in patients with RCC, scheduled to undergo primary, partial, or radical nephrectomy. The aim is to explore the use of OTL-38 and fluorescence imaging to observe RCC at the margins of resection in partial nephrectomy and in lymph node(s) or other metastases for radical nephrectomy. Methods: Currently two patients have participated in the trial to date with an accrual target of 20 patients. The first was a 67-year-old male with an incidental 2.2 cm right-sided renal mass, and the second was a 70-year-old male with an enlarging 2 cm renal mass. Per protocol, both patients were administered OTL-38 in the preoperative area 1 hour before the procedure. Subsequently, both procedures were performed with robotic assistance as per normal routine with the use of Firefly fluorescence to aid in observation of OTL-38 uptake. Results: Intraoperative guidance through OTL-38 demonstrated minimal to no uptake of the OTL-38 as seen by Firefly fluorescence (green color). Surprisingly, the normal renal parenchyma showed strong uptake of OTL-38 as seen by Firefly fluorescence. Both pathology reports revealed conventional clear cell RCC. Immunohistochemistry slides of the tumor revealed only mild staining for folate. In contrast, immunohistochemistry slides of the normal renal parenchyma in the surgical margin revealed a strongly positive stain for folate. Conclusions: In conclusion, our first two patients' renal tumors did not stain strongly for folate; however, the normal renal parenchyma did, which served as an intraoperative guide to confirm a negative margin. Further study of patients will reveal whether folate receptors are, in fact, predominant or not in renal cell cancer. No competing financial interests exist. Runtime of video: 5 mins Presented at the World Congress of Endourology 2016 in Capetown, South Africa.

The utility of considering right ventricular (RV) contractility and afterload as independent entities and summarising their balance or “coupling” using single beat methods has become widely appreciated [1–3]. Typically expressed as the ratio of end-systolic ventricular elastance (Ees, a load-independent measure of contractility), to arterial elastance (Ea, a lumped parameter measure of afterload) data suggest that when Ees/Ea reaches a critical threshold, the risk of cardiovascular decompensation begins to rise [4]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Heerdt reports other from RVMetrics, LLC, outside the submitted work; In addition, Dr. Heerdt has a patent Right ventricular monitoring device pending. Conflict of interest: Dr. Kheyfets has nothing to disclose. Conflict of interest: Dr. Charania has nothing to disclose. Conflict of interest: Dr. Elassal has nothing to disclose. Conflict of interest: Dr. Singh has nothing to disclose.

Postcircumcision bleeding can be the presenting symptom of a coagulopathy. A blood dyscrasia that is known but not documented in association with circumcision is neonatal alloimmune thrombocytopenia (NAIT). A 2-day-old male infant presented with postcircumcision bleeding. Platelet count was 5000 per microliter of blood. The child was treated conservatively with hematoma improvement. Few studies exist involving patients with coagulopathies who undergo circumcision. Our patient is the first to present with prolonged postcircumcision bleeding as the initial presentation of NAIT. NAIT and other coagulopathies that present as prolonged postcircumcision bleeding can often be managed successfully with conservative management.

Are researchers correct to assume individuals who walk during leisure-time do so mostly in their neighborhood? To address this question, we examined relationships between leisure-time walking and boundaries of participant- and researcher-defined neighborhoods. Door-to-door interviews were completed with 415 adults residing in a Midwestern, U.S. city. Participants self-reported physical activity and drew on a map their perceived neighborhoods and their typical leisure-time walking routes. We found that 134 participants walked in their neighborhoods at least once during the past week on the route they drew. Routes were used for 82.9% of the leisure-time walks and 67.9% of the route was within perceived neighborhood boundaries. Almost all of the routes (98.2%) were within a straight-line 2,000 m buffer around participants’ homes. The present study suggests leisure-time walking is neighborhood-based and certain researcher-defined areas are adequate when exploring this behavior. Route characteristics described in this study may have implications for initiatives promoting neighborhood walking.

The objective of this work is to develop a robust method for human abdominal aortic aneurysm (AAA) centerline detection that can contribute to the accurate computation of features for the prediction of AAA rupture risk. A semiautomatic algorithm is proposed for detecting the lumen centerline in contrast-enhanced abdominal computed tomography images based on online adaboost classifiers, which does not require prior image segmentation. The algorithm was developed and applied to thirty ruptured and thirty unruptured AAA image data sets and the tortuosities of the detected centerline were measured to assess the correlation between AAA tortuosity and the binary ruptured and unruptured labels. The lumen of each data set was segmented manually by a trained radiologist and the resulting centerlines of each data set were defined as the gold standard to evaluate the accuracy of the algorithm and to compare it against two widely used segmentation techniques. The average mean relative accuracy of the offline adaboost classifier is 91.9% with a standard deviation of 1.6%; for the online adaboost classifier it is 93.6% with a standard deviation of 1.9% (p

Upon its FDA approval in 2000, the da Vinci surgical system has permanently changed the landscape of minimally invasive surgery. However, the most effective method to train surgical trainees in this modern modality is not known. This chapter explores the various aspects inherent to the evolution of robotic surgical training.

Background/Objectives. The objective of this study was to evaluate the utility of circulating miRNAs as biomarkers of vascular function in pediatric pulmonary hypertension.Method. Fourteen pediatric pulmonary arterial hypertension patients underwent simultaneous right heart catheterization (RHC) and blood biochemical analysis. Univariate and stepwise multivariate linear regression was used to identify and correlate measures of reactive and resistive afterload with circulating miRNA levels. Furthermore, circulating miRNA candidates that classified patients according to a 20% decrease in resistive afterload in response to oxygen (O2) or inhaled nitric oxide (iNO) were identified using receiver-operating curves.Results. Thirty-two circulating miRNAs correlated with the pulmonary vascular resistance index (PVRi), pulmonary arterial distensibility, and PVRi decrease in response to O2and/or iNO. Multivariate models, combining the predictive capability of multiple promising miRNA candidates, revealed a good correlation with resistive (r=0.97,P2−tailed<0.0001) and reactive (r=0.86,P2−tailed<0.005) afterloads. Bland-Altman plots showed that 95% of the differences between multivariate models and RHC would fall within 0.13 (mmHg−min/L)m2and 0.0085/mmHg for resistive and reactive afterloads, respectively. Circulating miR-663 proved to be a good classifier for vascular responsiveness to acute O2and iNO challenges.Conclusion. This study suggests that circulating miRNAs may be biomarkers to phenotype vascular function in pediatric PAH.

In pulmonary hypertension (PH) diagnosis and management, many useful functional markers have been proposed that are unfeasible for clinical implementation. For example, assessing right ventricular (RV) contractile response to a gradual increase in pulmonary arterial (PA) impedance requires simultaneously recording RV pressure and volume, and under different afterload/preload conditions. In addition to clinical applications, many research projects are hampered by limited retrospective clinical data and could greatly benefit from simulations that extrapolate unavailable hemodynamics. The objective of this study was to develop and validate a 0D computational model, along with a numerical implementation protocol, of the RV–PA axis. Model results are qualitatively compared with published clinical data and quantitatively validated against right heart catheterization (RHC) for 115 pediatric PH patients. The RV–PA circuit is represented using a general elastance function for the RV and a three-element Windkessel initial value problem for the PA. The circuit mathematically sits between two reservoirs of constant pressure, which represent the right and left atriums. We compared Pmax, Pmin, mPAP, cardiac output (CO), and stroke volume (SV) between the model and RHC. The model predicted between 96% and 98% of the variability in pressure and 98–99% in volumetric characteristics (CO and SV). However, Bland Altman plots showed the model to have a consistent bias for most pressure and volumetric parameters, and differences between model and RHC to have considerable error. Future studies will address this issue and compare specific waveforms, but these initial results are extremely promising as preliminary proof of concept of the modeling approach.

Background— Left ventricular dysfunction, mediated by ventricular interdependence, has been associated with negative outcomes in children with pulmonary arterial hypertension (PAH). Considering the dilation of the pulmonary arteries as a paramount sign of PAH, we hypothesized that the ascending aorta will present signs of apparent stiffness in children with PAH and that this effect may be because of mechanical interaction with the dilated main pulmonary artery (MPA). Methods and Results— Forty-two children with PAH and 26 age- and size-matched controls underwent comprehensive cardiac magnetic resonance evaluation. Assessment of aortic stiffness was evaluated by measuring pulse wave velocity, aortic strain, and distensibility. Children with PAH had significantly increased pulse wave velocity in the ascending aorta (3.4 versus 2.3 m/s for PAH and controls, respectively; P =0.001) and reduced aortic strain (23% versus 29%; P P =0.02). Indexed MPA diameter correlated with pulse wave velocity ( P =0.04) and with aortic strain ( P =0.02). The ratio of MPA to aortic size correlated with pulse wave velocity ( P =0.0098), strain ( P =0.0099), and distensibility ( P =0.015). Furthermore, aortic relative area change was associated with left ventricular ejection fraction ( P =0.045) and ventricular–vascular coupling ratio ( P =0.042). Conclusions— Pediatric PAH patients have increased apparent ascending aortic stiffness, which was strongly associated with the degree of MPA distension. We speculate that distension of the MPA may play a major role in limiting full aortic expansion during systole, which modulates left ventricular performance and impacts systemic hemodynamics in pediatric PAH.

Our objective was to determine whether left ventricular (LV) vorticity (ω), the local spinning motion of a fluid element, correlated with markers of ventricular interdependency in pulmonary hypertension (PH). Maladaptive ventricular interdependency is associated with interventricular septal shift, impaired LV performance, and poor outcomes in PH patients, yet the pathophysiologic mechanisms underlying fluid-structure interactions in ventricular interdependency are incompletely understood. Because conformational changes in chamber geometry affect blood flow formations and dynamics, LV ω may be a marker of LV-RV (right ventricular) interactions in PH. Echocardiography was performed for 13 PH patients and 10 controls for assessment of interdependency markers, including eccentricity index (EI), and biventricular diastolic dysfunction, including mitral valve (MV) and tricuspid valve (TV) early and late velocities (E and A, respectively) as well as MV septal and lateral early tissue Doppler velocities (e'). Same-day 4-dimensional cardiac magnetic resonance was performed for LV E (early)-wave ω measurement. LV E-wave ω was significantly decreased in PH patients (P = 0.008) and correlated with diastolic EI (Rho = -0.53, P = 0.009) as well as with markers of LV diastolic dysfunction, including MV E(Rho = 0.53, P = 0.011), E/A (Rho = 0.56, P = 0.007), septal e' (Rho = 0.63, P = 0.001), and lateral e' (Rho = 0.57, P = 0.007). Furthermore, LV E-wave ω was associated with indices of RV diastolic dysfunction, including TV e' (Rho = 0.52, P = 0.012) and TV E/A (Rho = 0.53, P = 0.009). LV E-wave ω is decreased in PH and correlated with multiple echocardiographic markers of ventricular interdependency. LV ω may be a novel marker for fluid-tissue biomechanical interactions in LV-RV interdependency.

The capacity of a new drug containing ultra-low doses of antibodies to cannabinoid receptor type 1 (Dietressa) to reduce body weight gain in mice on a high-calorie diet was evaluated, possible mechanisms of drug action were analyzed, and its safety (abuse potential in the reaction of self-stimulation) was evaluated. Dietressa was not inferior to sibutramine in reducing body weight gain in mice and exhibited no abuse potential.

We compared two modifications of Vogel conflict test and assessed anxyolitic activity of two drugs: diazepam (benzodiazepine anxiolitic) and tenoten (ultra-low doses of antibodies to S-100 protein) in both modifications of the test. It was found that the intensity of anxiolitic effect of the drugs depends on the conditions of Vogel test.

Experiments on different models for sexual behavior (seasonal and age-related inhibition of sexual function, animals with initially reduced sexual function) showed that ultra-low doses of anti-NO-synthase antibodies (Impaza) stimulate sexual motivation and copulative behavior in rats. The effects of the drug on different aspects of sexual behavior depend on the chosen model.

Kardos, a preparation containing ultralow doses of antibodies to C-terminal fragment of type 1 receptor of angiotensin II, intragastrically administered to SHR rats with hereditary hypertension for 28 days reduced blood pressure by 14.8%. Kardos was not inferior to losartan and, in contrast to the latter reduced HR by 9.4%.