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Summary Here, we evaluate the efficacy of cryopreserved human embryonic stem cell (hESC)-derived corneal endothelial cells (CECs) to form a functional monolayer of corneal endothelium (CE) in rabbits and monkeys. We injected cryopreserved hESC-derived CECs into the anterior chamber of rabbits and monkeys either immediately after mechanical scraping of the central CE or a few days later when corneal edema developed. All preclinical models developed deturgesced and clear corneas following the injection of cryopreserved hESC-derived CECs and remained comparable to the corneas of the untreated eye. Confocal scanning microscopy confirmed an intact structure of hexagonal/polygonal cells and immunohistochemical analysis illustrated a monolayer expressing barrier and pump function proteins in the regenerated CE. The necropsy examination confirmed no remarkable change in multiple tissues assessed for teratoma formation. In conclusion, our data demonstrate the efficacy of cryopreserved hESC-derived CECs to form a functional CE on the denuded Descemet's membrane., Highlights • RNA-Seq confirmed similar transcriptomes of non-cryopreserved and cryopreserved hESC-derived CECs. • All preclinical models developed clear corneas following the injection of cryopreserved hESC-derived CECs. • The transparency of the regenerated corneas remained comparable to the corneas of the untreated eye. • Necropsy examination confirmed no remarkable change and/or teratoma formation in all preclinical models., In this article, Ali and colleagues show that intracameral injection of cryopreserved hESC-derived CECs can form a functional CE in rabbits and monkeys.

The indices of the pump function of the heart in teenagers with scoliosis of the 3d 4 th degree in rest and during stress test are studied. Disorders of the pump function of the heart take place in rest: the heart rate signficantly increases. During physical exercise in patients with scoliosis the increase of minute blood volume is less pronounced than in healthy persons and is realized by the increase of the heart rate and not by the stroke blood volume. It is less economical form of adaptation of the pump function of the heart to physical exercise. The functional reserves for increasing the minute blood volume, volumetric circulation rate in the response to physical exercise are decreased

Left ventricular septal pacing (LVSP) and left bundle branch pacing (LBBP) have been introduced to maintain or correct interventricular and intraventricular (dys)synchrony. LVSP is hypothesised to produce a fairly physiological sequence of activation, since in the left ventricle (LV) the working myocardium is activated first at the LV endocardium in the low septal and anterior free-wall regions. Animal studies as well as patient studies have demonstrated that LV function is maintained during LVSP at levels comparable to sinus rhythm with normal conduction. Left ventricular activation is more synchronous during LBBP than LVSP, but LBBP produces a higher level of intraventricular dyssynchrony compared to LVSP. While LVSP is fairly straightforward to perform, targeting the left bundle branch area may be more challenging. Long-term effects of LVSP and LBBP are yet to be determined. This review focuses on the physiology and practicality of LVSP and provides a guide for permanent LVSP implantation.

The adverse effects of ventricular dyssynchrony induced by right ventricular (RV) pacing has led to alternative pacing strategies, such as biventricular, His bundle (HBP), LV septal (LVSP) and left bundle branch pacing (LBBP). Given the overlap, LVSP and LBBP are also collectively referred to as left bundle branch area pacing (LBBAP). Although among these alternative pacing sites HBP is theoretically the ideal strategy as it maintains a physiological ventricular activation, its application requires more skills and is associated with the most complications. LBBAP, where the ventricular pacing lead is advanced through the interventricular septum to its left side, creates ventricular activation that is only slightly more dyssynchronous. Preliminary studies have shown that LBBAP is feasible, safe and encounters less limitations than HBP. Further studies are needed to differentiate between LVSP and LBBP with regard to acute functional and long-term clinical outcome.

Background: We recently demonstrated that a novel intra-ventricular membrane pump (IVMP) was able to increase the pump function of isolated beating porcine hearts. In follow-up, we now investigated the impact of the IVMP on myocardial oxygen consumption and total mechanical efficiency (TME) and assessed the effect of IVMP-support in acutely failing hearts. Methods: In 10 ex vivo beating porcine hearts, we studied hemodynamic parameters, as well as arterial and coronary venous oxygen content. We assessed cardiac power (CP), myocardial oxygen consumption (MVO2), and TME (CP divided by MVO2) under baseline conditions and during IVMP-support. Additionally, five isolated hearts were subjected to global hypoxia to investigate the effects of IVMP-support on CP under conditions of acute heart failure. Results: Under physiological conditions, baseline CP was 0.36 ± 0.10 W, which increased to 0.65 ± 0.16 W during IVMP-support (increase of 85% ± 24, p Conclusion: IVMP-support improved mechanical efficiency under physiological conditions, as the marked increase in cardiac performance only resulted in a modest increase in oxygen consumption. Moreover, the IVMP rapidly restored cardiac performance under conditions of acute pump failure. These observations warrant further study, to evaluate the effects of IVMP-support in in vivo animal models of acute cardiac pump failure.

Distal renal tubular acidosis is a rare renal tubular disorder characterized by hyperchloremic metabolic acidosis and impaired urinary acidification. Mutations in three genes (ATP6V0A4, ATP6V1B1 and SLC4A1) constitute a monogenic causation in 58–70% of familial cases of distal renal tubular acidosis. Recently, mutations in FOXI1 have been identified as an additional cause. Therefore, we hypothesized that further monogenic causes of distal renal tubular acidosis remain to be discovered. Panel sequencing and/or whole exome sequencing was performed in a cohort of 17 families with 19 affected individuals with pediatric onset distal renal tubular acidosis. A causative mutation was detected in one of the three “classical” known distal renal tubular acidosis genes in 10 of 17 families. The seven unsolved families were then subjected to candidate whole exome sequencing analysis. Potential disease causing mutations in three genes were detected: ATP6V1C2, which encodes another kidney specific subunit of the V-type proton ATPase (1 family); WDR72 (2 families), previously implicated in V-ATPase trafficking in cells; and SLC4A2 (1 family), a paralog of the known distal renal tubular acidosis gene SLC4A1. Two of these mutations were assessed for deleteriousness through functional studies. Yeast growth assays for ATP6V1C2 revealed loss-of-function for the patient mutation, strongly supporting ATP6V1C2 as a novel distal renal tubular acidosis gene. Thus, we provided a molecular diagnosis in a known distal renal tubular acidosis gene in 10 of 17 families (59%) with this disease, identified mutations in ATP6V1C2 as a novel human candidate gene, and provided further evidence for phenotypic expansion in WDR72 mutations from amelogenesis imperfecta to distal renal tubular acidosis.

espanolIntroduccion: La miocardiopatia del cirrotico es la disfuncion sistolica y/o diastolica del ventriculo izquierdo en reposo o estres, en ausencia de otras condiciones cardiovasculares que lo explique, y que empeora el pronostico post trasplante u otros procedimientos quirurgicos hepaticos. Objetivo: El objetivo del estudio fue caracterizar la funcion auricular izquierda con speckle tracking en pacientes cirroticos. Material y metodos: Se incluyeron 99 pacientes consecutivos con cirrosis hepatica de diferente etiologia. A todos pacientes se les realizo estudio ecocardiografico en reposo con medicion de la funcion ventricular y auricular isquierda con tecnicas tradicionales, mediciones tridimensionales y speckle tracking. Resultados: La mediana de edad fue de 50.9 anos y 40% de los pacientes fueron hombres. No se observaron alteraciones de la funcion sistolica del ventriculo izquierdo. El 27% de los pacientes presento disfuncion diastolica y dilatacion de la auricula izquierda, esta ultima con incremento significativo segun el estadio Child y se observaron alteraciones de la funcion de bomba de la auricula izquierda en el 29% de los casos. Conclusion: Los pacientes cirroticos presentan disfuncion diastolica ventricular izquierda y alteraciones de la funcion sistolica de la auricula izquierda medida por speckle tracking. EnglishBackground: Cirrhotic cardiomyopathy is the systolic and/or diastolic dysfunction of the left ventricle at rest or stress, in the absence of other cardiovascular conditions, and worsens the prognosis after transplant or other liver surgical procedures. Objective: The aim of the study was to characterize left atrial function with speckle tracking in cirrhotic patients. Methods: Ninety-nine consecutive patients with liver cirrhosis of different etiology were included in the study. All patients underwent rest echocardiographic evaluation with measurement of left ventricular and atrial function using traditional techniques, three-dimensional measurements and speckle tracking. Results: Median age was 50.9 years and 40% were men. No alterations of left ventricular systolic function were observed. Twenty-seven percent of patients had diastolic dysfunction and dilatation of the left atrium, the latter with a significant increase according to the Child stage and left atrial pump function was altered in 29% of cases. Conclusion: Cirrhotic patients present left ventricular diastolic dysfunction and alterations of left atrial systolic function measured by speckle tracking.

Background An increasing number of patients living with chronic ischemic cardiomyopathy (ICM) are potential candidates for cell therapy, including adipose tissue-derived mesenchymal stromal cells (ASC). However, proper assessment of clinical effects in relation to cellular effector mechanisms, such as angiogenesis, is currently lacking. Purpose To investigate the prognostic value of assessing angiogenesis non-invasively using novel PET imaging in terms of functional outcome after cell therapy in a homologous animal model of ICM. Methods Myocardial infarction was induced by permanent ligation of the left anterior descending coronary artery. Four weeks after infarction, the rats were scanned with [18F]-FDG and echocardiography, and based on left ventricular ejection fraction (LVEF) and infarct size randomized to allogeneic ASC treatment (n=14) or saline (n=9). Animals were treated using echo-guided trans-thoracic intramyocardial injections. Follow-up echocardiography was performed four weeks after treatment. Angiogenesis was assessed non-invasively using the [68Ga]-NODAGA-E[(cRGDyK)]2 (RGD) PET-tracer before treatment and two weeks after the treatment (Figure). The output was RGD-uptake by maximum standardized uptake value (SUVmax). Results RGD-uptake in the infarct area significantly decreased in the saline group (p=0.04), while this decline was not significant in the ASC group (p=0.58). There was no effect on LVEF of the cell therapy in this study (p=0.70). When the rats were grouped by RGD-uptake post treatment, the high RGD-uptake group (n=8) improved LVEF compared to the rats with medium or low RGD-uptake (n=15, p=0.04) irrespective of the treatment. This could indicate that non-invasive detection of a high degree of myocardial angiogenesis measured using RGD is predictive of improvement in cardiac pump function in ICM. Conclusions Following injection of ASC or saline, a high RGD-uptake precluded improvement in pump function. This is the first evidence of how uptake of the novel RGD tracer relates to changes in pump function in ICM and the results could affect the design of future clinical trials using regenerative therapy for ICM patients. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Aase and Ejnar Danielsens FondDoctor Sofus Carl Emil Friis and wife Olga Doris Friis' Scholarship Study design, RGD-uptake, and results

Exercise training (ET) is an important tool in the management of patients with chronic venous insufficiency (CVI). The objective of this article was to discuss the effects of ET on the calf pump, functional parameters, and quality of life of patients with mild and advanced CVI. A systematic review was conducted and eleven studies were included. In patients with mild CVI, ET was effective for improving venous reflux, muscle strength, ankle range of motion, and quality of life. In advanced CVI patients, ET increased ejection fraction, reduced residual volume fraction, and improved muscle strength and ankle range of motion, but did not change venous reflux indices or quality of life. It is concluded that ET is effective for improving calf pump function, muscle strength, and ankle range of motion in CVI. In patients with mild CVI, additional benefits were observed in quality of life. Resumo O treinamento físico é uma importante ferramenta no tratamento de pacientes com insuficiência venosa crônica. O objetivo foi discutir os efeitos do tratamento físico na bomba da panturrilha, os parâmetros funcionais e a qualidade de vida de pacientes com insuficiência venosa crônica leve e avançada. Uma revisão sistemática foi realizada, e 11 estudos foram incluídos. Na insuficiência venosa crônica leve, o treinamento físico foi eficaz na melhora do refluxo venoso, da força muscular, da amplitude de movimento do tornozelo e da qualidade de vida. Na insuficiência venosa crônica avançada, o treinamento físico aumentou a fração de ejeção, reduziu a fração de volume residual e melhorou a força muscular e amplitude de movimento do tornozelo, sem alterações nos índices de refluxo venoso e na qualidade de vida. Conclui-se que o treinamento físico é eficaz na melhoria da bomba da panturrilha, da força muscular e da amplitude de movimento do tornozelo na insuficiência venosa crônica. Em pacientes com insuficiência venosa crônica leve, foram encontrados benefícios adicionais na qualidade de vida.

Errors in healthcare are a leading cause of death in the United States. Equipment usability and user interfaces remain an area not fully elucidated. Infusion pumps play a vital role in care delivery, often essential for critical therapies. While pump function is comparatively simple, their programming, configuration, and form provide opportunity for error. Our purpose was to assess qualities nurses identified as important to pump operation by electronic survey. A self-developed usability survey was distributed to a random sample of 500 nurses, stratified by unit type and employed at the large academic quaternary care hospital. The overall response rate was 48% (n = 240). Descriptive and inferential statistics describe the responses and represent more than 5500 weekly infusions. Nurses described confident use of the system with some differences by unit type. Ninety percent of respondents indicated they have omitted use of the dose error reduction system, which should raise safety concerns. Users reported issues with the user interface and error prevention systems. Qualitative items elicited suggestions for improving aspects of the pump. Employing a usability survey in a clinical area proved to be a simple, inexpensive way to gather more information on the use and potential improvements of infusion pumps.

© American Heart Association, Inc. All rights reserved. Unauthorized use prohibited., The myocardium consists of numerous cell types embedded in organized layers of ECM (extracellular matrix) and requires an intricate network of blood and lymphatic vessels and nerves to provide nutrients and electrical coupling to the cells. Although much of the focus has been on cardiomyocytes, these cells make up, The authors acknowledge the following sources: National Institutes of Health (NIH) Grants HL113530 and HL-78825; the Hungarian National Research, Development, and Innovation Office (OTKA KH_17 125570, NVKP 16-1-2016-0017 National Heart Program, and VEKOP-2.3.2-16-2016-00002) and the Higher Education Institutional Excellence Programme of the Ministry of Human Capacities in Hungary, within the framework of the Therapeutic Development thematic programme of the Semmelweis University; G. Harold and Leila Y. Mathers Charitable Foundation and Universidad Catolica San Antonio de Murcia (UCAM); the ISCIII and FEDER (TerCel DTS15/00095, PI16/01123, and RD16/0011/0005) and ERANET II Cofund under H2020 (Nanoreheart); the Ministerio de Economía, Industria y Competitividad (SAF2017-84324- C2-R), Fundació La MARATÓ de TV3 (201502, 201516), CIBER Cardiovascular (CB16/11/00403), and AdvanceCat 2014.

Three main mechanisms contribute to global right ventricular (RV) function: longitudinal shortening, radial displacement of the RV free wall (bellows effect), and anteroposterior shortening (as a consequence of left ventricular contraction). Since the importance of these mechanisms may vary in different cardiac conditions, a technology being able to assess their relative influence on the global RV pump function could help to clarify the pathophysiology and the mechanical adaptation of the chamber. Previously, we have introduced our 3D echocardiography (3DE)-based solution—the Right VentrIcular Separate wall motIon quantificatiON (ReVISION) method—for the quantification of the relative contribution of the three aforementioned mechanisms to global RV ejection fraction (EF). Since then, our approach has been applied in several clinical scenarios, and its strengths have been demonstrated in the in-depth characterization of RV mechanical pattern and the prognostication of patients even in the face of maintained RV EF. Recently, various new features have been implemented in our software solution to enable the convenient, standardized, and more comprehensive analysis of RV function. Accordingly, in our current technical paper, we aim to provide a detailed description of the latest version of the ReVISION method with special regards to the volumetric partitioning of the RV and the calculation of longitudinal, circumferential, and area strains using 3DE datasets. We also report the results of the comparison between 3DE- and cardiac magnetic resonance imaging-derived RV parameters, where we found a robust agreement in our advanced 3D metrics between the two modalities. In conclusion, the ReVISION method may provide novel insights into global and also segmental RV function by defining parameters that are potentially more sensitive and predictive compared to conventional echocardiographic measurements in the context of different cardiac diseases.

Left atrial (LA) enlargement is present in the majority of adult heart transplant (HT) recipients. We used speckle-tracking echocardiography to investigate whether LA phasic function in HT patients is altered and explored its relationship to HT-related clinical variables. This study evaluated LA function in 112 clinically well HT patients and 40 healthy controls. Clinical data included recipient age at HT, donor age, ischemia time, left ventricular function, and biochemical indicators. Atrial deformation and volume indices were measured with two-dimensional and three-dimensional speckle-tracking echocardiography, respectively. Components of phasic atrial function were calculated and correlations to clinical variables were explored. Compared with controls, HT patients had worse LA reservoir, conduit, and pump function. LA reservoir function of the bicaval group was better than the biatrial group, but differences did not persist after adjustment for potential confounders. Among patients with HT, those with lower LAS-peak had an older recipient age, larger LA volume, as well as worse left ventricular systolic function than those patients with higher LAS-peak. However, E/e', biochemical indicators and donor-related information were similar across the quartiles of LA function. In HT cohort, we observed impairment in all phases of LA function, and LA reservoir function was decreased independent of surgical technique. LAS-peak was associated with worse left ventricular systolic function, which suggested that LA function may play an important role in HT patients.

Summary:. Treatment outcomes for lower extremity lymphedema (LEL) using multiple lymphaticovenular anastomoses (LVA) are still uncertain. Classification of progression of lymphedema by disease staging is a potential preoperative predictor of the efficacy of treatment, but it is difficult to judge progression of lymphedema objectively. Recent studies have indicated that lymph pump dysfunction, which reflects lymph transportation capacity, is associated with lymphedema progression. Indocyanine green (ICG) lymphography, a minimally invasive modality for pathophysiological assessment of lymphedema, can be used for rapid and objective measurement of ICG velocity (ICGv) and transit time to the knee (TTk), which are parameters of lymph transportation capacity, over a certain period. In the current study, we analyzed the relationship between these parameters and outcomes for LEL treated by multiple LVA. Thirty-four consecutive patients who underwent multiple LVA and ICG lymphography were enrolled in the study. The relationship of ICGv and TTk with the efficacy of treatment by LVA (LEL index reduction) was investigated using Pearson correlation coefficient analysis. LEL index reduction was more strongly correlated with ICGv than with TTk, whereas it was weakly correlated with both quantification methods of lymph pump function (r > 0.6). Both ICGv and TTk are objective and simple parameters that can measure lymph pump functions quickly. Lymph pump function, especially calculated with ICGv, might help predict the treatment efficacy and objective evaluation after therapeutic intervention using multiple LVA.

Background It is a challenging problem to differentiate obstructive hydronephrosis from noninvasive evaluation of renal pelvis and ureteral motility in patients. The purpose of this study was to explore the value of 640-slice dynamic volume CT (DVCT) in the quantitative measurement of upper urinary tract (UUT) pump function after acute unilateral lower ureteral obstruction in pigs. Methods In this study, a perfusion pig model was constructed by constant pressure perfusion testing of the renal pelvis and left nephrostomy. The perfusion and pressure measuring devices were connected to create a state of no obstruction and acute obstruction of the lower part of the left ureter. After successful modelling, continuous dynamic volume scanning of the bilateral renal excretion phase was performed with 640-slice DVCT, and pump functions of the renal pelvis and part of the upper ureter were calculated and analysed. No obstruction or acute obstruction of the lower part of the left ureter was observed. Pump functions of the renal pelvis and part of the upper ureter were determined. Results The results showed that after LUUT fistulostomy, the time difference between the average UUT volume and positive volume value increased gradually, and the calculated flow velocity decreased, which was significantly different from that of the RUUT. The volume difference of the LUUT increased significantly in mild obstruction. In the bilateral control, the volume change rate of the LUUT increased with mild obstruction and decreased with severe obstruction, and there was a significant difference between the left and right sides. Conclusion The continuous dynamic volume scan and measurement of 640-slice DVCT can obtain five pump function datasets of UUT in pigs with acute lower ureteral obstruction.

Background: Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome characterized by heart failure symptoms and signs, but normal or near-normal left ventricular ejection fraction (LV-EF). There are objective evidences of left ventricular systolic/diastolic dysfunctions and alteration of left atrial (LA) structure and functions. However, limited data are available on the association of LA functions with the severity of HFpEF. Methods: We assessed and analyzed LA/LV structure and functions in 61 patients with HFpEF with 2D echocardiography and two-dimensional speckle tracking echocardiographic technology (2D-STE). LA triphasic functions in subgroups with different classification of cardiac functions (NYHA II – IV) were compared. The correlation analysis of LA triphasic functions with LV systolic/diastolic functions was made with Pearson test. Results: Patients with HFpEF had impaired LV systolic/diastolic functions, and impaired LA triphasic functions compared with control subjects. LA global longitudinal strain (LA-GLS) and the left atrial systolic strain rate (LA-mSRs, reflecting LA reservoir function) were positively correlated with global LV longitudinal strain (LV-GLS) and E/e’; the longitudinal strain rate of the left atrium at the early diastole (LA-mSRe, reflecting LA conduit function) and the longitudinal strain rate of the left atrium at the late diastole (LA-mSRa, reflecting LA pump function) were inversely correlated with the LV-GLS and E/e’. The LA function is closely related with the NYHA classification in patients with HFpEF. Conclusion: LA phasic functions were significantly impaired in patients with HFpEF. It can be used as a marker for scaling the severity of HFpEF.

Nasolacrimal duct obstruction is commonly managed through dacryrocysorhinostomy (DCR), either through an external or endoscopic approach. Historically, the external approach was thought to have a higher success rate than the endoscopic approach. However, the literature now suggests that the endoscopic approach has comparable success with many advantages, such as avoidance of a cutaneous incision, preservation of the orbicularis oculi pump function, decreased operative time, and the ability to address concomitant intranasal pathology that may be contributing to the nasolacrimal duct obstruction, such as septal deviation or nasal polyposis. Despite the overall high success rate of both external and endoscopic DCR, there is an approximately 10% failure rate reported in the literature. These failures may be secondary to a variety of causes, such as inappropriate osteotomies, scarring, nasal pathology, functional failure, or proximal stenosis of the canalicular system. When failure occurs, revision endoscopic DCR or conjunctivodacryocystorhinostomy are important tools to readdress patient symptoms. When performed, meticulous surgical technique combined with a thorough knowledge of the anatomy of the nasolacrimal system is essential to optimize success.

The endothelial cell is a critical structure within the cornea and is responsible for maintaining corneal clarity through its pump function. Endothelial cells are lost over time naturally but can be injured medically, surgically, or as a part of various dystrophies. Monitoring of endothelial cells can be performed clinically or more formally with specular microscopy. In cases of significant compromise, endothelial cells can be transplanted by various endothelial keratoplasty techniques. The future pipeline is bright for possible endothelial cell regeneration and rehabilitation. This article reviews these topics in depth to provide a comprehensive look at the structure and function of the endothelial cell, etiologies of endothelial cell damage, detailed review of iatrogenic causes of endothelial cell loss, and management strategies.

Preventing the introduction of air while a mechanical circulatory support device is being implanted is critical for successful outcomes. A substantial amount of air may be introduced into the circulation during the pump-to-outflow and/or pump-to-inflow port connection, which can be detrimental to optimal pump function and long-term survival. We have developed a novel connecting sleeve that enables an airless connection of the continuous-flow total artificial heart to the conduits. Herein, we describe the device design and surgical techniques evaluated in vivo.

Heart failure (HF) has traditionally been defined by symptoms of fluid accumulation and poor perfusion, but it is now recognized that specific HF classifications hold prognostic and therapeutic relevance. Specifically, HF with reduced ejection fraction is characterized by reduced left ventricular systolic pump function and dilation and HF with preserved ejection fraction is characterized primarily by abnormal left ventricular filling (diastolic failure) with relatively preserved left ventricular systolic function. These forms of HF are distributed equally among patients with HF and likely require distinctly different strategies to mitigate the morbidity, mortality, and medical resource utilization of this disease. In particular, HF is a significant medical issue within the US Department of Veterans Affairs (VA) hospital system and constitutes a major translational research priority for the VA. Because a common underpinning of both HF with reduced ejection fraction and HF with preserved ejection fraction seems to be changes in the structure and function of the myocardial extracellular matrix, a conference was convened sponsored by the VA, entitled, "Targeting Myocardial Fibrosis in Heart Failure" to explore the extracellular matrix as a potential therapeutic target and to propose specific research directions. The conference was conceptually framed around the hypothesis that although HF with reduced ejection fraction and HF with preserved ejection fraction clearly have distinct mechanisms, they may share modifiable pathways and biological mediators in common. Inflammation and extracellular matrix were identified as major converging themes. A summary of our discussion on unmet challenges and possible solutions to move the field forward, as well as recommendations for future research opportunities, are provided.

3',5'-Cyclic guanosine monophosphate (cGMP) is a ubiquitous second messenger, which critically regulates cardiac pump function and protects from the development of cardiac hypertrophy by acting in various subcellular microdomains. Although clinical studies testing the potential of cGMP elevating drugs in patients suffering from cardiac disease showed promising results, deeper insight into the local actions of these drugs at the subcellular level are indispensable to inspire novel therapeutic strategies. Detailed information on the spatio-temporal dynamics of cGMP production and degradation can be provided by the use of fluorescent biosensors that are capable of monitoring this second messenger at different locations inside the cell with high temporal and spatial resolution. In this review, we will summarize how these emerging new tools have improved our understanding of cardiac cGMP signaling in health and disease, and attempt to anticipate future challenges in the field.

HeartMate II left ventricular assist device controllers provide data including pulsatility index, reflecting the relationship between pump function and hemodynamics. We propose that a higher pulsatility index at hospital discharge following implant may be associated with less vascular congestion and improved clinical outcomes. A retrospective analysis of 40 patients (age 59.2 ± 10.3 years) supported with the HeartMate II devices was conducted. Data revealed moderate Pearson correlations between pulsatility index at discharge and right atrial pressure, pulmonary artery systolic pressure, pulmonary artery diastolic pressure, mean pulmonary arterial pressure, and pulmonary capillary wedge pressure, respectively, post-surgery (median of 377 days), demonstrating a stronger relationship when analyzed for the EPC controller (n = 28) only (r = −.57, p

Contains fulltext : 229186.pdf (Publisher’s version ) (Closed access) The adverse effects of ventricular dyssynchrony induced by right ventricular (RV) pacing has led to alternative pacing strategies, such as biventricular, His bundle (HBP), LV septal (LVSP) and left bundle branch pacing (LBBP). Given the overlap, LVSP and LBBP are also collectively referred to as left bundle branch area pacing (LBBAP). Although among these alternative pacing sites HBP is theoretically the ideal strategy as it maintains a physiological ventricular activation, its application requires more skills and is associated with the most complications. LBBAP, where the ventricular pacing lead is advanced through the interventricular septum to its left side, creates ventricular activation that is only slightly more dyssynchronous. Preliminary studies have shown that LBBAP is feasible, safe and encounters less limitations than HBP. Further studies are needed to differentiate between LVSP and LBBP with regard to acute functional and long-term clinical outcome.

The nematode Caenorhabditis elegans is a filter feeder, which lives in various viscous habitats such as soil, the intestines of slugs, and rotting materials such as fruits and stems. C. elegans draws in suspensions of bacteria and separates bacteria from water using the pharyngeal pump. Although these worms often live in highly viscous habitats, it is still unclear how they survive in these environments by eating bacteria. In this study, we investigated the effects of suspension viscosity on the survival rate of malnutritioned worms by combining live imaging and scaling analyses. We found that survival rate decreased with increases in viscosity because the high viscosity suppressed the amount of food ingested. The same tendency was found in two feeding defective mutants, eat-6(ad467) and eat-6(ad997). We also found that the high viscosity weakened pump function, but the velocities in the pharynx were not zero, even in the most viscous suspensions. Finally, we estimated the amount of ingested food using scaling analyses, which provided a master curve of the experimental survival rates. These results illustrate that the survival rate of C. elegans worms is strongly dependent on the ingested bacteria per unit time associated with physical environments, such as the viscosity of food suspensions and the number density of bacteria. The pump function of the C. elegans pharynx is not completely lost even in fluids that have 105 times higher viscosity than water, which may contribute to their ability to survive around the world in highly viscous environments.

Funding Acknowledgements “This work was supported by a grant of Ministery of Research and Innovation, CNCS-UEFISCDI, project number PN-III-P1-1-TE-2016-0669, within PNCDI III” Background Differentiation between heart failure with preserved ejection fraction (HFpEF) and isolated diastolic dysfunction (DD) at rest is crucial, since the prognosis is different. Symptoms are often non-specific, while NTproBNP might not be available. Increased NTproBNP is predicted by none of the currently used transthoracic echocardiographic (TTE) parameters. However, assessment of left atrial (LA) function by speckle tracking echocardiography (STE) might be a potential new marker of increased LV filling pressure. Aim. To assess LA function by STE in HFpEF and DD, on top of the currently used TTE parameters, in order to establish the added value of LA deformation in the diagnosis of HFpEF. Methods 70 patients were enrolled prospectively: 40 with HFpEF (68 ± 9 yrs) and 30 with DD (60 ± 10 yrs). TTE was used to assess LV ejection fraction (LVEF), E/E’ ratio, left atrial volume index (LAVi), and systolic pulmonary arterial pressure (sPAP). STE was used to assess LA functions: reservoir function by strain from MVC to MVO (LASr) and positive strain rate (LASRr), conduit function by strain from MVO to onset of atrial contraction (LAScd) and early negative strain rate during conduit phase (LASRcd), and LA pump function by negative strain at MVC (LASct) and late negative strain rate during atrial contraction phase (LASRct). NTproBNP was measured in all patients. Results HFpEF patients had significantly higher LVEF, NTproBNP, E/E’ ratio, and sPAP, but similar LAVi compared to DD, suggesting higher LV filling pressure (Table). LA reservoir and conduit function were similar. However, LA pump function was significantly lower in HFpEF, expressed by LASRct (Tabel). NTproBNP correlated with E/E’ ratio, sPAP, and LASRct (all r = 0.44, p 125pg/ml was LASRct (r = 0.60, r2 =0.30, p 125pg/ml (Figure). Conclusion LA pump function is the only predictor of NTproBNP > 125pg/ml. This parameter should be incorporated in the current protocols for the diagnosis of HFpEF. Group (N) NTproBNP ng/ml LVEF (%) E/E’ sPAP (mmHg) LAVi (ml/m2) LASr (%) LASRr LAScd (%) LASRcd LASRct HFpEF (40) 329 ± 383 62 ± 6 10.4 ± 2.7 34 ± 11 40 ± 9 25 ± 4 1.28 ± 0.3 11.6 ± 5.5 -1.37 ± 0.5 -1.07 ± 0.6 DD (30) 37 ± 26 57 ± 8 7.5 ± 1.8 23 ± 7 39 ± 11 26 ± 6 1.26 ± 0.3 11.2 ± 3.6 -1.5 ± 0.6 -1.76 ± 0.7 P value 0.001 0.008 Abstract 409 Figure.

Many types of neurologic injury are known to affect the cardiovascular system. Both rhythm and pump function can be dramatically affected. In this chapter, we review the cardiovascular changes that can be seen after neurologic injury and the specific neurologic diseases most commonly associated with those changes. This chapter covers hypertension, cardiomyopathy, shock, arrhythmias, and myocardial ischemia. These neurocardiogenic changes are important to diagnose, understand, and manage in order to simultaneously optimize neurologic recovery and cardiovascular function. Recognition of these neurocardiovascular connections can help neurointensivists and cardiologists best understand the underlying driving forces behind hemodynamic instabilities that can be seen in patients after acute neurologic injury.

To date, no viable therapeutic options exist for the effective and sustained reversal of cardiac failure, other than heart transplantation and mechanical circulatory assist devices. Therefore, divergent strategies aiming at the de novo formation of contractile tissue, as a prerequisite for the restoration of cardiac pump function, are currently being pursued. Clinical trials involving the transplantation of somatic progenitor cells failed. The search for alternative cell-based strategies to combat the consequences of ischemic injury has sparked widespread interest in the genetic and pharmacologic reprogramming of fibroblasts into cardiomyocytes, harnessing the abundant in vivo pool of cardiac fibroblasts. Here, we provide a comprehensive overview of in vitro and in vivo cardiac reprogramming studies identified in an extensive literature search. We systematically review and evaluate feasibility, efficiency, and reproducibility of the different technologies currently being explored. Finally, we discuss potential safety issues deduced from preclinical studies and identify obstacles that must be overcome before clinical translation.-Klose, K., Gossen, M., Stamm, C. Turning fibroblasts into cardiomyocytes: technological review of cardiac transdifferentiation strategies.

BACKGROUND Dacryocystorhinostomy (DCR) is the gold standard surgical treatment for nasolacrimal duct obstruction. External DCR is the traditional approach (EXT-DCR); however, the advent of minimally invasive surgeries and the development of optic fiber and laser technologies have made it possible to perform laser transcanalicular DCR (T-DCR), a minimally invasive procedure. This study measured the fluorescein transit time (FTT) after EXT-DCR or T-DCR to evaluate the lacrimal drainage and lacrimal pump function after these two types of DCR. SUBJECTS AND METHODS A cross-sectional study of 50 patients who underwent EXT-DCR (EXT-DCR Group) or T-DCR (T-DCR Group), who were anatomically patent upon irrigation, with a minimum 6 months of follow up. The patients' FTT was measured; it was defined as the time from the instillation of the dye into conjunctival sac to its free flow from the rhinostomy site. This evaluation was performed through nasal endoscopy performed intranasally with a blue filter that enabled the faster detection of fluorescein from the ostium site. The mean FTTs of the two groups were compared using the two-sided Student's unpaired t-test. Other variables such as sex, age, previous lacrimal sac size, and the site and shape of the rhinostomy were evaluated to determine their possible relationships with FTT. RESULTS The EXT-DCR group had 80% female patients at a mean age of 58 years. The T-DCR group had the same percentage of female patients (80%) and a mean age of 56 years. The mean FTT group was 47.48 sec in the EXT-DCR and 33.04 sec in the T-DCR group. Functional success was 88% in both groups. CONCLUSION FTT in the DCR-T Group was significantly lower than in the EXT-DCR Group. No other variables exhibited a statistically significant correlation with FTT. Lacrimal drainage was found to be better after T-DCR than after EXT-DCR, results which show that this procedure could prevent lacrimal pump damage.

Corneal endothelium is a single layer of hexagonal cells that maintains the corneal transparency and thickness through its barrier and pump function. For the treatment of corneal endothelial dysfunction, the transplantation of tissue-engineered corneal endothelium and direct injection of cultured corneal endothelial cells were developed because of the severe shortage of donor cornea worldwide. However, the technique difficulty or safety risk still remained. In this study, we report a novel mini-sheet injection for the cultured corneal endothelial cell transplantation and compare with the effects of single-cell injection in rabbit model. Compared with the reported single-cell injection, mini sheets promoted the adhesion and tight junction formation after injection. Rabbit corneal clarity and thickness were rapidly recovered after 7 days of mini-sheet injection, compared with 14 days of single-cell injection. Moreover, typical endothelial morphology was observed as early as 7 days after the mini-sheet injection, whereas until 21 days after the single-cell injection. These results demonstrate that the novel mini-sheet injection of corneal endothelial cells exhibited rapid adhesion, tight junction formation, and corneal clarity recovery, which may represent a more efficient method for the transplantation of cultured corneal endothelial cells.

The complex nature of interaction between the heart and the circulation was well recognized among the early nineteenth-century physiologists, and despite numerous technical challenges associated with “opening of the circuit,” attempts were made to investigate the mechanical behavior of the heart itself. The ideas that led to the development and application of this radical experiment played a key role in the understanding of the mechanical and energetic function of the heart which remains incomplete. Further discussed are: recirculating and non-recirculating isolated heart preparations; Otto Frank’s and Ernest Starling’s isolated heart preparations and original formulation of the “law of the heart”; similarity between the isolated heart preparation and the hydraulic ram as a unique model of heart’s mechanical action; quantification of ventricular pump function by the “three element Windkessel”; the “physiological enigma” of the high myocardial basal metabolic rate and its low mechanical efficiency; length-dependent activation of the cardiac muscle and the reformulation of the “law of the heart” in terms of myocardial energetics; and the conceptual drawbacks of the total artificial hearts and relative success of the ventricular assist and continuous flow devices.

Coronary artery disease (CAD) develops when coronary arteries are unable to supply oxygen-rich blood to the heart due to the accumulation of cholesterol plaque on the inner walls of the arteries. Chronic insufficient blood flow leads to the complications, including angina and heart failure. In addition, acute plaque rupture may lead to vessel occlusion, causing a heart attack. Thus, it is encouraged to have regular check-ups to diagnose CAD early and avert complications. The electrocardiogram (ECG) is a widely used diagnostic tool to study the electrical activity of the heart. However, ECG signals are highly chaotic, complex, and non-stationary in their behaviour. It is laborious, and requires expertise, to visually interpret these signals. Hence, the computer-aided detection system (CADS) is developed to assist clinicians to interpret the ECG signals fast and reliably. In this work, we have employed sixteen entropies to extract the various hidden signatures from ECG signals of normal healthy persons as well as patients with CAD. We observed that the majority of extracted entropy features showed lower values for CAD patients compared to normal subjects. We believe that there is one possible reason which could be the decreased in the variability of ECG signals is associated with reduced heart pump function.

Growing concerns have been expressed regarding cardiovascular performance in modern farm pigs, which has been proposed as a critical factor contributing to the reduced adaptability of modern pigs to stress. Here we tested the hypothesis that cardiac dimensions and pump function in modern heavy farm pigs are disproportionally low for their body weight, and investigated potential underlying mechanisms. The results from the present study indeed demonstrate disproportionally low values for stroke volume and cardiac output in pigs with bodyweights over 150 kg. Importantly, these low values were not the result of impaired left ventricular (LV) systolic contractile function, but were due to a disproportionally small LV end-diastolic volume. The latter was associated with changes in determinants of LV passive stiffness, including (i) an increase in LV myocardial collagen, (ii) a shift from the compliant N2BA titin isoform towards the stiff N2B, and (iii) a marked elevation of aortic blood pressure. Taken together, these results demonstrate reduced pumping capacity of the hearts of heavy modern pigs, due to structural abnormalities in the LV myocardium.