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Finger vein recognition methods, as emerging biometric technologies, have attracted increasing attention in identity verification due to their high accuracy and live detection capabilities. However, as privacy protection awareness increases, traditional centralized finger vein recognition algorithms face privacy and security issues. Federated learning, a distributed training method that protects data privacy without sharing data across endpoints, is gradually being promoted and applied. Nevertheless, its performance is severely limited by heterogeneity among datasets. To address these issues, this paper proposes a dual-decoupling personalized federated learning framework for finger vein recognition (DDP-FedFV). The DDP-FedFV method combines generalization and personalization. In the first stage, the DDP-FedFV method implements a dual-decoupling mechanism involving model and feature decoupling to optimize feature representations and enhance the generalizability of the global model. In the second stage, the DDP-FedFV method implements a personalized weight aggregation method, federated personalization weight ratio reduction (FedPWRR), to optimize the parameter aggregation process based on data distribution information, thereby enhancing the personalization of the client models. To evaluate the performance of the DDP-FedFV method, theoretical analyses and experiments were conducted based on six public finger vein datasets. The experimental results indicate that the proposed algorithm outperforms centralized training models without increasing communication costs or privacy leakage risks.

In bivalves and gastropods, ventricle contraction causes a negative pressure in the auricles and increases venous return from the afferent oblique vein (AOV): the constant-volume (CV) mechanism. The flow in the AOV should be a pulsative flow synchronized with the ventricular contraction. The flow in the heart and adjacent vessels of Mytilus galloprovincialis were measured by magnetic resonance imaging to confirm this hypothesis. Under a regular heartbeat, pulsative flows in the AOV and branchial vessels (BVs) were almost completely synchronized with the flow in the aorta, while filling of the ventricle was in the opposite phase. Flows in the BVs were directed to the posterior direction, and a pair of BVs in the gill axes (the efferent BVs) were connected to the AOV. Based on the images of the whole pathway of the AOV in an oblique slice, we confirmed that haemolymph flow was evoked from the efferent BVs and flow into the ventricle via the auricle was completed in a single heartbeat. Therefore, the walls of the AOV and BVs could resist negative transmural pressure caused by the ventricular contraction. In conclusion, the auricle, the AOV and the BVs, including the gill filaments, act as a suction pump. The pulsative venous return is driven by the negative pressure of the AOV as in the CV mechanism, and the negative pressure in the efferent BVs could draw haemolymph from the sinus via the gill and the afferent BVs. Therefore, Mytilus can start and stop its heartbeat as necessary., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Imaging deep haemodynamics non-invasively remains a quest. Although optical imaging techniques can be used to measure blood flow, they are generally limited to imaging within ∼1 mm below the skin's surface. Here we show that such optical diffusion limit can be broken through by leveraging the spatial heterogeneity of blood and its photoacoustic contrast. Specifically, successive single-shot wide-field photoacoustic images of blood vessels can be used to visualize the frame-to-frame propagation of blood and to estimate blood flow speed and direction pixel-wise. The method, which we named photoacoustic vector tomography (PAVT), allows for the quantification of haemodynamics in veins more than 5 mm deep, as we show for regions in the hands and arms of healthy volunteers. PAVT may offer advantages for the diagnosis and monitoring of vascular diseases and for the mapping of the function of the circulatory system., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Aqueous humor (AQH) is a transparent fluid with characteristics similar to those of the interstitial fluid, which fills the eyeball posterior and anterior chambers and circulates in them from the sites of production to those of drainage. The AQH volume and pressure homeostasis is essential for the trophism of the ocular avascular tissues and their normal structure and function. Different AQH outflow pathways exist, including a main pathway, quite well defined anatomically and referred to as the conventional pathway, and some accessory pathways, more recently described and still not fully morphofunctionally understood, generically referred to as unconventional pathways. The conventional pathway is based on the existence of a series of conduits starting with the trabecular meshwork and Schlemm's Canal and continuing with a system of intrascleral and episcleral venules, which are tributaries to veins of the anterior segment of the eyeball. The unconventional pathways are mainly represented by the uveoscleral pathway, in which AQH flows through clefts, interstitial conduits located in the ciliary body and sclera, and then merges into the aforementioned intrascleral and episcleral venules. A further unconventional pathway, the lymphatic pathway, has been supported by the demonstration of lymphatic microvessels in the limbal sclera and, possibly, in the uvea (ciliary body, choroid) as well as by the ocular glymphatic channels, present in the neural retina and optic nerve. It follows that AQH may be drained from the eyeball through blood vessels (TM-SC pathway, US pathway) or lymphatic vessels (lymphatic pathway), and the different pathways may integrate or compensate for each other, optimizing the AQH drainage. The present review aims to define the state-of-the-art concerning the structural organization and the functional anatomy of all the AQH outflow pathways. Particular attention is paid to examining the regulatory mechanisms active in each of them. The new data on the anatomy and physiology of AQH outflow pathways is the key to understanding the pathophysiology of AQH outflow disorders and could open the way for novel approaches to their treatment., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

There is increasing interest in how immune cells in the meninges-the membranes that surround the brain and spinal cord-contribute to homeostasis and disease in the central nervous system 1,2 . The outer layer of the meninges, the dura mater, has recently been described to contain both innate and adaptive immune cells, and functions as a site for B cell development 3-6 . Here we identify organized lymphoid structures that protect fenestrated vasculature in the dura mater. The most elaborate of these dural-associated lymphoid tissues (DALT) surrounded the rostral-rhinal confluence of the sinuses and included lymphatic vessels. We termed this structure, which interfaces with the skull bone marrow and a comparable venous plexus at the skull base, the rostral-rhinal venolymphatic hub. Immune aggregates were present in DALT during homeostasis and expanded with age or after challenge with systemic or nasal antigens. DALT contain germinal centre B cells and support the generation of somatically mutated, antibody-producing cells in response to a nasal pathogen challenge. Inhibition of lymphocyte entry into the rostral-rhinal hub at the time of nasal viral challenge abrogated the generation of germinal centre B cells and class-switched plasma cells, as did perturbation of B-T cell interactions. These data demonstrate a lymphoid structure around vasculature in the dura mater that can sample antigens and rapidly support humoral immune responses after local pathogen challenge., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Mean circulatory filling pressure, venous return curve, and Guyton's graphical analysis are basic concepts in cardiovascular physiology. However, some medical students may not know how to view and interpret or understand them adequately. To deepen students' understanding of the graphical analysis, in place of having to perform live animal experiments, we developed an interactive cardiovascular simulator, as a self-learning tool, as a web application. The minimum closed-loop model consisted of a ventricle, an artery, resistance, and a vein, excluding venous resistance. The simulator consists of three modules: setting (parameters and simulation modes), calculation, and presentation. In the setting module, the user can interactively customize model parameters, compliances, resistance, Emax of the ventricular contractility, total blood volume, and unstressed volume. The hemodynamics are calculated in three phases: filling (late diastole), ejection (systole), and flow (early diastole). In response to the user's settings, the simulator graphically presents the hemodynamics: the pressure-volume relations of the artery, vein, and ventricle, the venous return curves, and the stroke volume curves. The mean filling pressure is calculated at approximately 7 mmHg at the initial setting. The venous return curves, linear and concave, are dependent on the venous compliance. The hemodynamic equilibrium point is marked on the crossing point of venous return curve and the stroke volume curve. Users can interactively do discovery learning, and try and confirm their interests and get their questions answered about hemodynamic concepts by using the simulator., (© 2024. The Author(s).)

Vascular diseases of the legs are highly prevalent and constitute an important part of medical curricula. The understanding of these diseases relies on strongly interwoven aspects of vascular physiology and vascular medicine. We aimed to connect these within a horizontally integrated laboratory class on vascular physiology of the leg that was designed in cooperation between the departments of physiology and vascular surgery. Conceptually, we applied examination techniques of vascular medicine to visualize physiological parameters that are altered by the most frequent diseases. This facilitates integrative discussions on malfunctions, trains diagnostic skills, and bridges to vascular medicine. In four experiments, we use oscillometry and impedance venous occlusion plethysmography to address key aspects of the arterial and venous system of the legs: 1 ) arterial pulse wave, 2 ) arterial systolic blood pressure, 3 ) venous capacitance and venous outflow, and 4 ) reactive hyperemia. After the experiments, physiological vascular function, the associated diseases, their impact on the recorded parameters, and diagnostic options are discussed. To allow reproduction, we describe the course structure and the experimental setup in detail. We present the experimental data of a cohort of medical students and document learning success and student satisfaction. All experiments were feasible and provided robust data on physiologically and clinically relevant vascular functions. The activity was perceived positively by the students and led to a substantial improvement of knowledge. With this work, we offer a template for reproduction or variation of a proven concept of horizontally integrated teaching of vascular physiology of the leg. NEW & NOTEWORTHY This article presents an integrative laboratory class on vascular physiology bridging to vascular medicine. The four experiments rely on oscillometry and venous occlusion plethysmography. We describe in detail this new class regarding structure, experimental setup, and experimental procedure, and we give insight into the applied materials. Moreover, we present the experimental data of 74 students and a quantitative evaluation of the students' learning success and acceptance.

Tissue factor (TF) is an evolutionarily conserved protein necessary for initiation of hemostasis. Zebrafish have two copies of the tissue factor gene (f3a and f3b) as the result of an ancestral teleost fish duplication event (so called ohnologs). In vivo physiologic studies of TF function have been difficult given early lethality of TF knockout in the mouse. We used genome editing to produce knockouts of both f3a and f3b in zebrafish. Since ohnologs arose through sub- or neofunctionalization, they can unmask unknown functions of non-teleost genes and could reveal whether mammalian TF has developmental functions distinct from coagulation. Here we show that a single copy of either f3a or f3b is necessary and sufficient for normal lifespan. Complete loss of TF results in lethal hemorrhage by 2-4 months despite normal embryonic and vascular development. Larval vascular endothelial injury reveals predominant roles for TFa in venous circulation and TFb in arterial circulation. Finally, we demonstrate that loss of TF predisposes to a stress-induced cardiac tamponade independent of its role in fibrin formation. Overall, our data suggest partial subfunctionalization of TFa and TFb. This multigenic zebrafish model has the potential to facilitate study of the role of TF in different vascular beds., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: J.A.S. has been a consultant for Bayer, Takeda, CSL Behring, Sanofi, and HEMA Biologics. All other authors declare they have no competing interests., (Copyright: © 2022 Grzegorski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Immature arteriovenous fistula (AVF) is a critical problem in patients with chronic kidney disease (CKD) after creation. Exercise with 30% maximum voluntary contraction (MVC) encourages vascular functions in other populations. It is unknown which exercise type is superior on maturation in the CKD population. We compare effects of isometric (ISM) and isotonic (IST) hand exercise training, both at 30% MVC, on AVF maturation and grip strength in patients with CKD., Methods: Fifty patients with CKD were randomized into the ISM program or IST program (25 per group). Each group performed exercise program at intensity of 30% MVC every day for 10 weeks. Cephalic vein (CV) and brachial artery diameters, brachial blood flows, and grip strength were measured at weeks 0, 2, 6, and 10 of the program. The number of patients meeting clinical and ultrasound maturation were evaluated at weeks 2, 6, and 10., Results: At weeks 6 and 10 of the programs, the ISM group had greater CV diameters (week 6, 7.1 ± 1.2 vs 6.2 ± 1.0 mm; week 10, 7.1 ± 1.0 vs 6.2 ± 1.1 mm) than the IST group. Compared with the IST group, the ISM group had a higher number of patients meeting ultrasound maturation at weeks 2 (IST/ISM, 8/2), 6 (IST/ISM, 16/8), and 10 (IST/ISM, 21/12), and clinical maturation at week 10 (IST/ISM, 25/18). No adverse events were observed throughout the study., Conclusions: At 30% MVC, ISM is more effective at promoting increases in CV diameter and maturation than IST. Both exercise types are feasible and safe for patients with CKD after AVF creation., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies have established the role of various tissue compartments in the kinetics of inhaled anesthetic uptake and elimination. The role of normal lungs in inhaled anesthetic kinetics is less understood. In juvenile pigs with normal lungs, the authors measured desflurane and sevoflurane washin and washout kinetics at three different ratios of alveolar minute ventilation to cardiac output value. The main hypothesis was that the ventilation/perfusion ratio (VA/Q) of normal lungs influences the kinetics of inhaled anesthetics., Methods: Seven healthy pigs were anesthetized with intravenous anesthetics and mechanically ventilated. Each animal was studied under three different VA/Q conditions: normal, low, and high. For each VA/Q condition, desflurane and sevoflurane were administered at a constant, subanesthetic inspired partial pressure (0.15 volume% for sevoflurane and 0.5 volume% for desflurane) for 45 min. Pulmonary arterial and systemic arterial blood samples were collected at eight time points during uptake, and then at these same times during elimination, for measurement of desflurane and sevoflurane partial pressures. The authors also assessed the effect of VA/Q on paired differences in arterial and mixed venous partial pressures., Results: For desflurane washin, the scaled arterial partial pressure differences between 5 and 0 min were 0.70 ± 0.10, 0.93 ± 0.08, and 0.82 ± 0.07 for the low, normal, and high VA/Q conditions (means, 95% CI). Equivalent measurements for sevoflurane were 0.55 ± 0.06, 0.77 ± 0.04, and 0.75 ± 0.08. For desflurane washout, the scaled arterial partial pressure differences between 0 and 5 min were 0.76 ± 0.04, 0.88 ± 0.02, and 0.92 ± 0.01 for the low, normal, and high VA/Q conditions. Equivalent measurements for sevoflurane were 0.79 ± 0.05, 0.85 ± 0.03, and 0.90 ± 0.03., Conclusions: Kinetics of inhaled anesthetic washin and washout are substantially altered by changes in the global VA/Q ratio for normal lungs., (Copyright © 2021, the American Society of Anesthesiologists. All Rights Reserved.)

The flow patterns of red blood cells through the spleen are intimately linked to clearance of senescent RBCs, with clearance principally occurring within the open flow through the red pulp and slits of the venous sinus system that exists in humans, rats, and dogs. Passage through interendothelial slits (IESs) of the sinus has been shown by MacDonald et al. (Microvasc Res 33:118-134, 1987) to be mediated by the caliber, i.e., slit opening width, of these slits. IES caliber within a given slit of a given sinus section has been shown to operate in an asynchronous manner. Here, we describe a model and simulation results that demonstrate how the supporting forces exerted on the sinus by the reticular meshwork of the red pulp, combined with asymmetrical contractility of stress fibers within the endothelial cells comprising the sinus, describe this vital and intriguing behavior. These results shed light on the function of the sinus slits in species such as humans, rats, and dogs that possess sinusoidal sinuses. Instead of assuming a passive mechanical filtering mechanism of the IESs, our proposed model provides a mechanically consistent explanation for the dynamically modulated IES opening/filtering mechanism observed in vivo. The overall perspective provided is also consistent with the view that IES passage serves as a self-protective mechanism in RBC vesiculation and inclusion removal., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A method motivated by the eye's aqueous veins is described for the imaging and strain calculation within soft biological tissues. A challenge to the investigation of the biomechanics of the aqueous vein-perilimbal sclera tissue complex is resolution of tissue deformations as a function of intraocular pressure and the subsequent calculation of strain (a normalized measure of deformation). The method involves perfusion of the eye with a contrast agent during conduction of non-invasive, optical resolution photoacoustic microscopy. This imaging technique permits three-dimensional displacement measurements of tracked points on the inner walls of the veins which are used in a finite element model to determine the corresponding strains. The methods are validated against two standard strain measurement methods. Representative porcine globe perfusion experiments are presented that demonstrate the power of the method to determine complex strain fields in the veins dependent on intraocular pressure as well as vein anatomy. In these cases, veins are observed to move radially outward during increases in intraocular pressure and to possess significant spatial strain variation, possibly influenced by their branching patterns. To the authors' knowledge, these are the only such quantitative, data driven, calculations of the aqueous vein strains available in the open literature., (© 2021. The Author(s).)

Background: This study aims to determine the phlebotomy and procedural outcomes using a vein assessment tool (VAT) in Double Dose Platelet (DDP) collections by apheresis., Methods: VAT was based on assessing vein visibility, palpation and size with maximum score of 12 and the least being 0 and the scores were graded as adequate and inadequate. A vein-viewer was used for studying cubital vein patterns (type 1-5). Phlebotomy outcome was defined based on need for re-puncture. Procedural outcomes in terms of target yield attained and RBC reinfusion completed. Chi square test and Mann- Whitney U test were used to assess the vein score and pattern against phlebotomy and procedural outcome., Results: Out of 200 DDP collections, the phlebotomy was successful in 88 % with good procedural outcome in 94 % donations. The cut off in VAT scores for successful phlebotomy was ≥8 (AUC: 70 %). Median vein scores of the arm selected for phlebotomy was 9 and graded adequate in 154 (77 %) donations.Odds for successful phlebotomy was 3.7 times higher when donors had an adequate VAT grades(p = 0.003). Procedural outcomes was favourable when at least one arm had adequate VAT grade when compared to both arms being inadequate (98 % vs 82 %; p < 0.001). Phlebotomy failure was more with first time apheresis donors than repeat apheresis donors (p = 0.014)., Conclusion: This study indicated that a VAT score with a cut off of ≥8 had better phlebotomy and procedural outcomes in DDP collections and that donor with at least one arm having the VAT score of ≥8 are preferred for DDP collections., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Personalized tissue engineered vascular grafts are a promising advanced therapy medicinal product alternative to autologous or synthetic vascular grafts utilized in blood vessel bypass or replacement surgery. We hypothesized that an individualized tissue engineered vein (P-TEV) would make the body recognize the transplanted blood vessel as autologous, decrease the risk of rejection and thereby avoid lifelong treatment with immune suppressant medication as is standard with allogenic organ transplantation. To individualize blood vessels, we decellularized vena cava from six deceased donor pigs and tested them for cellular removal and histological integrity. A solution with peripheral blood from the recipient pigs was used for individualized reconditioning in a perfusion bioreactor for seven days prior to transplantation. To evaluate safety and functionality of the individualized vascular graft in vivo, we transplanted reconditioned porcine vena cava into six pigs and analyzed histology and patency of the graft at different time points, with three pigs at the final endpoint 4-5 weeks after surgery. Our results showed that the P-TEV was fully patent in all animals, did not induce any occlusion or stenosis formation and we did not find any signs of rejection. The P-TEV showed rapid recellularization in vivo with the luminal surface covered with endothelial cells. In summary, the results indicate that P-TEV is functional and have potential for use as clinical transplant grafts., (© 2021 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons Ltd.)

Introduction: The consequences on the cervicofacial venous circulation of major cervicofacial vein ligations are poorly known. We aimed to highlight by using Doppler Ultrasound flow differences in the cervicofacial venous network in the case of unilateral or bilateral ligation of main venous collector trunks (external jugular vein [EJV] and internal jugular vein [IJV]) METHODS: A Doppler ultrasound was performed on 10 healthy volunteers, 8 patients with previous bilateral ligation of the EJV, 8 with a unilateral ligation of the EJV, and 8 with a unilateral ligation of the EJV and IJV, after modified radical neck dissection. The diameter, the flow direction and the peak systolic velocity (PSV) of the superficial temporal vein, the facial vein (FV) and the IJV were measured., Results: Healthy patients had a similar right and left PSV for all the veins studied, with always antegrade flows. Patients with previous ligations had some significant right/left differences and retrograde flows., Conclusion: A redistribution of venous blood flow on the contralateral side of the face and neck seems to take place in the case of unilateral ligation of the EJV and/or IJV. Retrograde flows are sometimes observed in the case of previous ligation of the EJV and/or IJV and might compromise the success of venous microanastomoses., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Defining the hemodynamic response to volume therapy is integral to managing critically ill patients with acute circulatory failure, especially in the absence of cardiac index (CI) measurement. This study aimed at investigating whether changes in central venous-to-arterial CO 2 difference (Δ-ΔPCO 2 ) and central venous oxygen saturation (ΔScvO 2 ) induced by volume expansion (VE) are reliable parameters to define fluid responsiveness in sedated and mechanically ventilated septic patients. We prospectively studied 49 critically ill septic patients in whom VE was indicated because of circulatory failure and clinical indices. CI, ΔPCO 2 , ScvO 2 , and oxygen consumption (VO 2 ) were measured before and after VE. Responders were defined as patients with a > 10% increase in CI (transpulmonary thermodilution) after VE. We calculated areas under the receiver operating characteristic curves (AUCs) for Δ-ΔPCO 2 , ΔScvO 2 , and changes in CI (ΔCI) after VE in the whole population and in the subgroup of patients with an increase in VO 2 (ΔVO 2 ) ≤ 10% after VE (oxygen-supply independency). Twenty-five patients were fluid responders. In the whole population, Δ-ΔPCO 2 and ΔScvO 2 were significantly correlated with ΔCI after VE (r =  - 0.30, p = 0.03 and r = 0.42, p = 0.003, respectively). The AUCs for Δ-ΔPCO 2 and ΔScvO 2 to define fluid responsiveness (increase in CI > 10% after VE) were 0.76 (p < 0.001) and 0.68 (p = 0.02), respectively. In patients with ΔVO 2  ≤ 10% (n = 36) after VE, the correlation between ΔScvO 2 and ΔCI was 0.62 (p < 0.001), and between Δ-ΔPCO 2 and ΔCI was - 0.47 (p = 0.004). The AUCs for Δ-ΔPCO 2 and ΔScvO 2 were 0.83 (p < 0.001) and 0.73 (p = 0.006), respectively. In these patients, Δ-ΔPCO 2  ≤ -37.5% after VE allowed the categorization between responders and non-responders with a positive predictive value of 100% and a negative predictive value of 60%. In sedated and mechanically ventilated septic patients with no signs of tissue hypoxia (oxygen-supply independency), Δ-ΔPCO 2 is a reliable parameter to define fluid responsiveness., (© 2021. The Author(s).)

Arteries and veins form in a stepwise process that combines vasculogenesis and sprouting angiogenesis. Despite extensive data on the mechanisms governing blood vessel assembly at the single-cell level, little is known about how collective cell migration contributes to the organization of the balanced distribution between arteries and veins. Here, we use an endothelial-specific zebrafish reporter, arteriobow, to label small cohorts of arterial cells and trace their progeny from early vasculogenesis throughout arteriovenous remodeling. We reveal that the genesis of arteries and veins relies on the coordination of 10 types of collective cell dynamics. Within these behavioral categories, we identify a heterogeneity of collective cell motion specific to either arterial or venous remodeling. Using pharmacological blockade, we further show that cell-intrinsic Notch signaling and cell-extrinsic blood flow act as regulators in maintaining the heterogeneity of collective endothelial cell behavior, which, in turn, instructs the future territory of arteriovenous remodeling., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

The measurement of vascular function in isolated vessels has revealed important insights into the structural, functional, and biomechanical features of the normal and diseased cardiovascular system and has provided a molecular understanding of the cells that constitutes arteries and veins and their interaction. Further, this approach has allowed the discovery of vital pharmacological treatments for cardiovascular diseases. However, the expansion of the vascular physiology field has also brought new concerns over scientific rigor and reproducibility. Therefore, it is appropriate to set guidelines for the best practices of evaluating vascular function in isolated vessels. These guidelines are a comprehensive document detailing the best practices and pitfalls for the assessment of function in large and small arteries and veins. Herein, we bring together experts in the field of vascular physiology with the purpose of developing guidelines for evaluating ex vivo vascular function. By using this document, vascular physiologists will have consistency among methodological approaches, producing more reliable and reproducible results.

The endothelial glycocalyx is a dynamic structure integral to blood vessel hemodynamics and capable of tightly regulating a range of biological processes (ie, innate immunity, inflammation, and coagulation) through dynamic changes in its composition of the brush structure. Evaluating the specific roles of the endothelial glycocalyx under a range of pathophysiologic conditions has been a challenge in vitro as it is difficult to generate functional glycocalyces using commonly employed 2D cell culture models. We present a new multi-height microfluidic platform that promotes the growth of functional glycocalyces by eliciting unique shear stress forces over a continuous human umbilical vein endothelial cell monolayer at magnitudes that recapitulate the physical environment in arterial, capillary and venous regions of the vasculature. Following 72 hours of shear stress, unique glycocalyx structures formed within each region that were distinct from that observed in short (3 days) and long-term (21 days) static cell culture. The model demonstrated glycocalyx-specific properties that match the characteristics of the endothelium in arteries, capillaries and veins, with respect to surface protein expression, platelet adhesion, lymphocyte binding and nanoparticle uptake. With artery-to-capillary-to-vein transition on a continuous endothelial monolayer, this in vitro platform is an improved system over static cell culture for more effectively studying the role of the glycocalyx in endothelial biology and disease., (© 2021 Federation of American Societies for Experimental Biology.)

Background: Arteriovenous fistulae (AVF) are the preferred mode of vascular access for hemodialysis. Before use, AVF remodel by thickening and dilating to achieve a functional conduit via an adaptive process characterized by expression of molecular markers characteristic of both venous and arterial identity. Although signaling via EphB4, a determinant of venous identity, mediates AVF maturation, the role of its counterpart EphrinB2, a determinant of arterial identity, remains unclear. We hypothesize that EphrinB2 signaling is active during AVF maturation and may be a mechanism of venous remodeling., Methods: Aortocaval fistulae were created or sham laparotomy was performed in C57Bl/6 mice, and specimens were examined on Days 7 or 21. EphrinB2 reverse signaling was activated with EphB4-Fc applied periadventitially in vivo and in endothelial cell culture medium in vitro. Downstream signaling was assessed using immunoblotting and immunofluorescence., Results: Venous remodeling during AVF maturation was characterized by increased expression of EphrinB2 as well as Akt1, extracellular signal-regulated kinases 1/2 (ERK1/2), and p38. Activation of EphrinB2 with EphB4-Fc increased phosphorylation of EphrinB2, endothelial nitric oxide synthase, Akt1, ERK1/2, and p38 and was associated with increased diameter and wall thickness in the AVF. Both mouse and human endothelial cells treated with EphB4-Fc increased phosphorylation of EphrinB2, endothelial nitric oxide synthase, Akt1, ERK1/2, and p38 and increased endothelial cell tube formation and migration., Conclusions: Activation of EphrinB2 signaling by EphB4-Fc was associated with adaptive venous remodeling in vivo while activating endothelial cell function in vitro. Regulation of EphrinB2 signaling may be a new strategy to improve AVF maturation and patency., (Published by Elsevier Inc.)

Extracorporeal membrane oxygenation (ECMO) support has a high incidence of both bleeding and thrombotic complications. Despite clear differences in patient characteristics and pathologies between veno-venous (VV) and veno-arterial (VA) ECMO support, anticoagulation practices are often the same across modalities. Moreover, there is very little data on their respective coagulation profiles and comparisons of thrombin generation in these patients. This study compares the coagulation profile and thrombin generation between patients supported with either VV and VA ECMO. A prospective cohort study of patients undergoing VA and VV ECMO at an Intensive care department of a university hospital and ECMO referral centre. In addition to routine coagulation testing and heparin monitoring per unit protocol, thromboelastography (TEG), multiplate aggregometry (MEA), calibrated automated thrombinography (CAT) and von-Willebrand's activity (antigen and activity ratio) were sampled second-daily for 1 week, then weekly thereafter. VA patients had significantly lower platelets counts, fibrinogen, anti-thrombin and clot strength with higher d-dimer levels than VV patients, consistent with a more pronounced consumptive coagulopathy. Thrombin generation was higher in VA than VV patients, and the heparin dose required to suppress thrombin generation was lower in VA patients. There were no significant differences in total bleeding or thrombotic event rates between VV and VA patients when adjusted for days on extracorporeal support. VA patients received a lower median daily heparin dose 8500 IU [IQR 2500-24000] versus VV 28,800 IU [IQR 17,300-40,800.00]; < 0.001. Twenty-eight patients (72%) survived to hospital discharge; comprising 53% of VA patients and 77% of VV patients. Significant differences between the coagulation profiles of VA and VV patients exist, and anticoagulation strategies for patients of these modalities should be different. Further research into the development of tailored anticoagulation strategies that include the mode of ECMO support need to be completed.

Purpose: Intraoperative bleeding from the pelvic venous structures is one of the most serious complications of total pelvic exenteration with distal sacrectomy. The purpose of this study was to investigate the topographic anatomy of these veins and the potential source of the bleeding in cadaver dissections., Methods: We dissected seven cadavers, focusing on the veins in the surgical resection line for total pelvic exenteration with distal sacrectomy., Results: The presacral venous plexus and the dorsal vein complex are thin-walled, plexiform, and situated on the line of resection. The internal iliac vein receives blood from the pelvic viscera and the perineal and the gluteal regions and then crosses the line of resection as a high-flow venous system. It has abundant communications with the presacral venous plexus and the dorsal vein complex., Conclusion: The anatomical features of the presacral venous plexus, the dorsal vein complex, and the internal iliac vein make them highly potential sources of bleeding. Surgical management strategies must consider the anatomy and hemodynamics of these veins carefully to perform this procedure safely.

Background: Delayed identification of infiltration and dysfunction of peripheral intravenous (PIV) access can lead to serious consequences during general anesthesia in children. This preliminary study aimed to describe the application of precordial Doppler ultrasound during general anesthesia in children to detect and confirm the correct PIV access and to evaluate the accuracy of this method., Methods: This was a single-center, preliminary study that was conducted in children (<18 years) who were scheduled for elective surgeries between October 2019 and March 2020. Rater anesthesiologists judged the change in precordial Doppler sound (S test) before and after injection of 0.5 mL/kg of normal saline (NS) via PIV. Blood flow velocity before and after NS injection was recorded, and multiple cutoff points were set to analyze the accuracy of detecting the infiltration and dysfunction of PIV catheter (V test)., Results: The total incidence of peripheral infiltration and dysfunction of PIV catheter was 7/512 (1.4%). In the S test, the sensitivity, specificity, positive and negative likelihood ratios, and area under the receiver-operating characteristic curves (AUCs) were 5/7 (71.4%; 95% confidence interval [CI], 29.0%-96.3%), 490/505 (97.0%; 95% CI, 95.1%-98.3%), 24.0, 0.29, and 0.84, respectively. The V test showed that the reasonable threshold of blood flow velocity change was 1.0 m/s, with sensitivity, specificity, positive and negative likelihood ratios, and AUC of 4/7 (57.1%; 95% CI, 18.4%-90.1%), 489/505 (96.8%; 95% CI, 94.9%-98.2%), 18.0 and 0.44, and 0.84, respectively., Conclusions: This preliminary study demonstrated that precordial Doppler ultrasound is a feasible, easy-to-use, and noninvasive technique with good accuracy to confirm the correct PIV access during general anesthesia in children. However, its accuracy requires further evaluation., Competing Interests: The authors have declared that no competing interests exist.

Sepsis and septic shock remain the leading cause of death in intensive care units. Despite significant improvements in sepsis management, mortality still ranges between 20 and 30%. Novel treatment approaches in order to reduce sepsis-related multiorgan failure and death are urgently needed. Robust animal models allow for one or multiple treatment approaches as well as for testing their effect on physiological and molecular parameters. In this article, a simple animal model is presented. First, general anesthesia is induced in animals either with the use of volatile or by intraperitoneal anesthesia. After placement of an intravenous catheter (tail vein), tracheostomy, and insertion of an intraarterial catheter (tail artery), mechanical ventilation is started. Baseline values of mean arterial blood pressure, arterial blood oxygen saturation, and heart rate are recorded. The injection of lipopolysaccharides (1 milligram/kilogram body weight) dissolved in phosphate-buffered saline induces a strong and reproducible inflammatory response via the toll-like receptor 4. Fluid corrections as well as the application of norepinephrine are performed based on well-established protocols. The animal model presented in this article is easy to learn and strongly oriented towards clinical sepsis treatment in an intensive care unit with sedation, mechanical ventilation, continuous blood pressure monitoring, and repetitive blood sampling. Also, the model is reliable, allowing for reproducible data with a limited number of animals in accordance with the 3R (reduce, replace, refine) principles of animal research. While animal experiments in sepsis research cannot easily replaced, repetitive measurements allow for a reduction of animals and keeping septic animals anesthetized diminishes suffering.

Background: Circulating fatty acid-binding protein 4 (FABP4) is a marker for various diseases. It would be highly useful to have simple and less invasive techniques for the assessment of FABP4 concentrations in the clinical research setting. The purpose of the present study was to assess the concordance of circulating FABP4 concentrations in venous and capillary blood both at rest and immediately after acute exercise in healthy young males., Results: Thirty-eight healthy young male adults aged from 19 to 25 years (mean age, 20.8 ± 1.2 years) were recruited. Paired blood samples were taken from the cubital vein (venous) and fingertip (capillary) blood at rest (resting state) and immediately after incremental exercise (exercising state). Blood samples were analyzed to determine the circulating FABP4 concentration using an enzyme-linked immunosorbent assay. Pearson's correlation coefficients for circulating FABP4 concentrations between venous and capillary blood samples indicated a strong positive correlation in both the resting and exercising state (resting state: r = 0.982, exercising state: r = 0.989, both p < 0.001). The mean FABP4 concentration was similar between venous and capillary blood in the resting state (p = 0.178), whereas it was significantly higher in capillary blood than in venous blood in the exercising state (p < 0.001). Furthermore, Bland-Altman plots showed a non-significant bias (- 0.07 ± 0.61 ng/mL, p = 0.453) in the resting state, whereas a significant bias (- 0.45 ± 0.61 ng/mL, p < 0.001) was observed in the exercising state., Conclusions: These results indicate that capillary blood sampling can slightly overestimate circulating FABP4 concentrations under a physiologically dynamic state. However, the association between the venous and capillary blood in terms of FABP4 concentration was very strong, suggesting that capillary blood sampling can detect changes in FABP4 concentration in both physiologically steady and dynamic states.

We describe here a novel protocol that sequentially combines venous followed by arterial occlusions to determine muscle blood flow and O 2 uptake from a single measurement point using near-infrared spectroscopy (NIRS) during handgrip exercise. NIRS data were obtained from the flexor digitorum superficialis (FDS) muscle on the dominant arm of 15 young, healthy adults (3 women; 26 ± 7 years; 78.6 ± 9.1 kg). Participants completed a series of 15-s static handgrip contractions at 20, 40 and 60% of maximal voluntary contraction (MVC) immediately followed by either a: (i) venous occlusion (VO); (ii); arterial occlusion (AO); or venous then arterial occlusion (COMBO). Each condition was repeated 3 times for each exercise-intensity. The concordance correlation coefficient (CCC) and robust linear mixed effects modeling were used to determine measurement agreement between vascular occlusion conditions. FDS muscle blood flow ([Formula: see text]) and conductance ([Formula: see text]) demonstrated strong absolute agreement between VO and COMBO trials from rest up to 60%MVC, as evidenced by high values for CCC (> 0.82) and a linear relationship between conditions that closely approximated the line-of-identity (perfect agreement). Conversely, although FDS muscle O 2 uptake ([Formula: see text]) displayed "substantial" to "near perfect" agreement between methods across exercise intensities (i.e., CCC > 0.80), there was a tendency for COMBO trials to underestimate [Formula: see text] by up to 7%. These findings indicate that the COMBO method provides valid estimates of [Formula: see text] and, to a slightly lesser extent, [Formula: see text] at rest and during static handgrip exercise up to 60%MVC. Practical implications and suggested improvements of the method are discussed.

Introduction: The ratio of cerebrospinal fluid (CSF) glucose and blood glucose is of major relevance, conducting to the diagnosis of hypoglycorrhachia, which is a sign of neuroinfection, as well as a number of neurological diseases of genetic or neoplastic etiology. Glucose in capillary sample (glucometry) is a low cost, readily available technique, as compared to venous glucose. This study aims to compare glucometry to venous glucose in the diagnosis of hypoglycorrhachia in pediatric population., Methods: Prospective cross-sectional study based on data obtained from lumbar punctures in the period from February 2017 to January 2019 in a specialized pediatric institution in Colombia., Results: 97 patients were analyzed, aged 1 month to 17 years old, mean 7.67 years, 52 (53.61%) were female. 26 (26.8%) were diagnosed with hypoglycorrhachia. Pearson correlation coefficient for absolute venous and capillary glucose was 0.54, and 0.55 for the ratios of CSF glucose/venous glucose and CSF glucose/glucometry, which support a linear correlation between the variables in both, absolute values and ratios. Intraclass correlation coefficient was calculated for both, the venous glucose and glucometry ratios, which was 0.52, revealing a moderate agreement among the tests. Sensitivity and specificity of CSF glucose/glucometry, as compared to gold standard are 73.1% and 60.6% respectively; whereas predictive positive value (PPV) and negative predictive value (NPV), were 40.4% and 86.0%., Conclusion: Glucometry cannot replace the glucose in venous sample in the diagnosis of hypoglycorrhachia in children., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Mixed venous oxygen (O 2 ) saturation ([Formula: see text]) is an important measure for evaluating the sufficiency of cardiac output (CO) relative to whole body O 2 consumption (V̇o 2 ), while clinical use is limited to the required invasive catheterization. According to Fick's equation, V̇o 2 (mL/min) = CO (L/min) × Hb (g/dL) × 1.36 (mL/g) × ([Formula: see text] - [Formula: see text])/10 (Hb = hemoglobin concentration, [Formula: see text] = arterial blood O 2 saturation). Because V̇o 2 , CO, Hb, and [Formula: see text] can be measured noninvasively with expired gas analysis, echocardiography, a simple blood test, and percutaneous O 2 saturation, respectively, [Formula: see text] can be calculated noninvasively. We hypothesized that noninvasively calculated [Formula: see text] shows a significant correlation and agrees well with invasively measured [Formula: see text]. In 47 patients (29 men; mean age, 70 ± 12 yr) who underwent right heart catheterization, [Formula: see text] was directly measured by sampling pulmonary artery blood. Noninvasively calculated [Formula: see text] was also obtained by the method described above. The calculated [Formula: see text] was significantly correlated with the measured [Formula: see text] ( r  = 0.79, P < 0.001) and was significantly smaller than the measured [Formula: see text] (70 ± 5.1 vs. 72.1 ± 4.9%, P < 0.001). Bias at [Formula: see text] was -2.2% (95% confidence interval, -3.2 to -1.1%) with limits of agreement from -9.5 to 5.2%, demonstrating acceptable agreement. The optimal cutoff value of calculated [Formula: see text] was 69% for reduced measured [Formula: see text] < 70% with an area under the curve of 0.94. Reduced calculated [Formula: see text] < 69% indicated a sensitivity of 92.9% and a specificity of 90.9% for reduced measured [Formula: see text] < 70%. Noninvasive [Formula: see text] calculated from echocardiography, expired gas analysis, percutaneous arterial blood O 2 saturation, and hemoglobin level significantly correlated and agreed well with direct [Formula: see text] measured by catheterization. This novel method allows for practical evaluation of [Formula: see text] to assess the sufficiency of CO according to whole body metabolism. NEW & NOTEWORTHY Clinical use of mixed venous oxygen saturation ([Formula: see text]) is limited to the required invasive procedure. With Fick's equation, expired gas analysis, echocardiography, simple blood tests, and percutaneous oxygen saturation, [Formula: see text] can be calculated noninvasively. We hypothesized that noninvasively calculated [Formula: see text] shows a significant correlation and agrees well with invasively measured [Formula: see text]. The present study examined the relationship between measured [Formula: see text] and calculated [Formula: see text] in patients who underwent right heart catheterization and demonstrated acceptable agreement. This novel method can expand the indication of evaluating [Formula: see text].

Objectives: 1) To elucidate the role of collector channels in the aqueous humor outflow pathway 2) To suggest anatomic and functional methods of imaging collector channels in-vitro and in-vivo and 3) To discuss the role of such imaging modalities in the surgical management of glaucoma., Methods: A thorough literature search was conducted on databases for studies published in English regarding the available methods to determine the role of collecting channels in normal and glaucomatous patients and to assess their patency., Results: Intraocular pressure (IOP) exists as a balance between aqueous humor production and aqueous humor outflow. Collector channels are an essential anatomical constituent of the distal portion of the conventional aqueous humor outflow pathway. There are different surgical options for glaucoma management and with the recent advances in Schlemm's canal-based surgeries, collector channel's patency became a key factor in determining the optimum management for the glaucomatous eye. The advent of anatomic imaging methods has improved the ability to visualize collector channel morphology in-vitro, including swept-source optical coherence tomography (SS-OCT), spectral domain optical coherence tomography (SD-OCT), micro-computed tomography (micro CT), new immunohistochemistry techniques and scanning electron microscopy. The recent advent of real-time assessment of collector channel patency (including evaluation of episcleral venous outflow, observation of episcleral venous fluid wave, and tracer studies utilizing fluorescein, indocyanine green, and trypan blue) has been validated by the aforementioned anatomic imaging modalities., Conclusions: New modalities of in-vitro and in-vivo studies of collector channels provide promise to aid in the assessment of collector channel patency and individualization of surgical management for glaucoma patients.

P130CAS/BCAR1 belongs to the CAS family of adaptor proteins, with important regulatory roles in cell migration, cell cycle control, and apoptosis. Previously, we and others showed that P130CAS mediates VEGF-A and PDGF signalling in vitro, but its cardiovascular function in vivo remains relatively unexplored. We characterise here a novel deletion model of P130CAS in zebrafish. Using in vivo microscopy and transgenic vascular reporters, we observed that while bcar1-/- zebrafish showed no arterial angiogenic or heart defects during development, they strikingly failed to form the caudal vein plexus (CVP). Endothelial cells (ECs) within the CVP of bcar1-/- embryos produced fewer filopodial structures and did not detach efficiently from neighbouring cells, resulting in a significant reduction in ventral extension and overall CVP area. Mechanistically, we show that P130Cas mediates Bmp2b-induced ectopic angiogenic sprouting of ECs in the developing embryo and provide pharmacological evidence for a role of Src family kinases in CVP development.

Platelets upregulate the generation of thrombin and reinforce the fibrin clot which increases the incidence risk of venous thromboembolism (VTE). However, the role of platelets in the pathogenesis of venous cardiovascular diseases remains hard to quantify. An experimentally validated model of thrombin generation dynamics is formulated. The model predicts that a high platelet count increases the peak value of generated thrombin as well as the endogenous thrombin potential (ETP) as reported in experimental data. To investigate the effects of platelets density, shear rate, and wound size on the initiation of blood coagulation, we calibrate a previously developed model of venous thrombus formation and implement it in 3D using a novel cell-centered finite-volume solver. We conduct numerical simulations to reproduce in vitro experiments of blood coagulation in microfluidic capillaries. Then, we derive a reduced one-equation model of thrombin distribution from the previous model under simplifying hypotheses and we use it to determine the conditions of clotting initiation on the platelet count, the shear rate, and the plasma composition. The initiation of clotting also exhibits a threshold response to the size of the wounded region in good agreement with the reported experimental findings., Competing Interests: The authors have declared that no competing interests exist.

Background: Non-Invasive Venous waveform Analysis (NIVA) is novel technology that captures and analyzes changes in venous waveforms from a piezoelectric sensor on the wrist for hemodynamic volume assessment. Complex cranial vault reconstruction is performed in children with craniosynostosis and is associated with extensive blood loss, potential life-threatening risks, and significant morbidity. In this preliminary study, we hypothesized that NIVA will provide a reliable, non-invasive, quantitative assessment of intravascular volume changes in children undergoing complex cranial vault reconstruction., Objective: To present proof-of-concept results of a novel technology in the pediatric population., Methods: The NIVA prototype was placed on each subject's wrist, and venous waveforms were collected intraoperatively. Estimated blood loss and fluid/blood product administration were recorded in real time. Venous waveforms were analyzed into a NIVA value and then correlated, along with mean arterial pressure (MAP), to volume changes. Concordance was quantified to determine if the direction of change in volume was similar to the direction of change in MAP or change in NIVA., Results: Of 18 patients enrolled, 14 had usable venous waveforms, and there was a significant correlation between change in NIVA value and change in volume. Change in MAP did not correlate with change in volume. The concordance between change in MAP and change in volume was less than the concordance between change in NIVA and change in volume., Conclusion: NIVA values correlate more closely to intravascular volume changes in pediatric craniofacial patients than MAP. This initial study suggests that NIVA is a potential safe, reliable, non-invasive quantitative method of measuring intravascular volume changes for children undergoing surgery., Competing Interests: The intellectual property associated with this novel technology is held by Vanderbilt University Medical Center (VUMC) and licensed to VoluMetrix. VoluMetrix was not a funding source for this study. KMH is Founder, CEO and President of VoluMetrix and an inventor on intellectual property in the field of venous waveform analysis assigned to VUMC and licensed to VoluMetrix. CMB is Founder and CMO of VoluMetrix and an inventor on intellectual property in the field of venous waveform analysis assigned to VUMC and licensed to VoluMetrix. BDA, is CSO and owns stock in VoluMetrix and is an inventor on intellectual property in the field of venous waveform analysis assigned to VUMC and licensed to VoluMetrix and is married to the COO of VoluMetrix. JW is the Senior Software Engineer and owns stock in VoluMetrix. SSE was former CEO of VoluMetrix and an inventor on intellectual property in the field of venous waveform analysis assigned to VUMC and licensed to VoluMetrix. The remaining authors have no conflicts of interest to declare. These declarations do not alter our adherence to PLOS ONE policies on sharing data and materials.

Aim: This study was designed to quantify the influence of blood as test medium compared to water in cannula bench performance assessment., Methods: An in vitro circuit was set-up with silicone tubing between two reservoirs. The test medium was pumped from the lower reservoir by centrifugal pump to the upper reservoir. The test-cannula was inserted in a silicone tube connected between the lower reservoir and the centrifugal pump. Flow rate and pump inlet-pressure were measured for wall-less versus thin-wall cannula using a centrifugal pump in a dynamic bench-test for an afterload of 40-60 mmHg using two media: blood 10 g/dL and 5.6 g/dL and water 0 g/dL., Results: The wall-less cannula showed significantly higher flows rates as compared to the thin-wall cannula (control), with both hemoglobin concentrations and water. Indeed, for a target volume of 200-250 mL of blood (Hg 10 g/dL) in the upper reservoir, the cannula outlet pressure (P) was -14 ± 14 mmHg versus -18 ± 11 mmHg for the wall-less and control respectively; the cannula outlet flow rate (Q) was 3.91 ± 0.41 versus 3.67 ± 0.45 L/min, respectively. At the same target volume but with a Hg of 5.7 g/dL, P was -16 ± 12 mmHg versus -19 ± 12 mmHg and Q was 4 ± 0.1 versus 4 ± 0.4 L/min for the wall-less cannula and control respectively. Likewise, P and Q values with water were -1 mmHg versus -0.67 ± 0.58 mmHg and 4.17 ± 0.45 L/min versus 4.08 ± 0.47 L/min for the wall-less and control respectively., Conclusion: Walls-less cannula showed 5.6% less pump inlet-pressure differences calculated between blood and water, as compared to that of thin-wall cannula (-21 times). Flow differences were 6% and 10% for the walls-less and thin-wall cannula respectively. We conclude that testing the cannula performance with water is a good scenario and can overestimate the flow by a 10%. However, superiority for wall-less is preserved with both water and blood.

Circulating miRNAs have received extensive attention as non-invasive biomarkers for prediction and diagnosis of disease. However, most samples have been obtained from peripheral venous blood. To evaluate whether peripheral venous miRNAs represent circulating miRNAs from all blood vessels under a given condition, such as aging, we compared the miRNA profiles of venous and arterial plasma between young and aged rats by Illumina next-generation sequencing. The DEseq2 tool was used to obtain differentially-expressed miRNAs. We observed 105 aging-related deregulated miRNAs in vein and 62 in artery, which were highly associated with cell survival and inflammation, respectively. On the other hand, the young and aged groups exhibited a unique arterial-venous bias. There were 54 differentially-expressed miRNAs in the young group and 42 in the aged group; only 8 miRNAs were shared. Further transcriptional factors enrichment analysis found that the shared miRNAs could be partially upregulated by NF-κB and SIRT1. These transcriptional factors could be organ-specific and/or regulated in physiological and aging states as possible causal factors. This study suggested the potential application of circulating miRNAs, which reflect the systematic response to certain conditions, such as aging, and the importance of origin selection for candidate circulating miRNAs.

Purpose: To characterize the effects of netarsudil on the aqueous humor outflow tract distal to the trabecular meshwork (TM). We hypothesized that netarsudil increases outflow facility in eyes with and without circumferential ab interno trabeculectomy (AIT) that removes the TM., Methods: Sixty-four porcine anterior segment cultures were randomly assigned to groups with (n = 32) and without circumferential AIT (n = 32). Cultures were exposed to 0.1, 1, and 10 μM netarsudil (N = 8 eyes per concentration). For each concentration, IOP and vessel diameters were compared with their respective pretreatment baselines. Outflow tract vessel diameters were assessed by spectral-domain optical coherence tomography (SDOCT) and rendered in 4D (XYZ time series)., Results: Netarsudil at 1 μM reduced IOP both in eyes with TM (- 0.60 ± 0.24 mmHg, p = 0.01) and in eyes without TM (- 1.79 ± 0.42 mmHg, p < 0.01). At this concentration, vessels of the distal outflow tract dilated by 72%. However, at 0.1 μM netarsudil elevated IOP in eyes with TM (1.59 ± 0.36 mmHg, p < 0.001) as well as in eyes without TM (0.23 ± 0.32 mmHg, p < 0.001). Vessels of the distal outflow tract constricted by 31%. Similarly, netarsudil at a concentration of 10 μM elevated IOP both in eyes with TM (1.91 ± 0.193, p < 0.001) and in eyes without TM (3.65 ± 0.86 mmHg, p < 0.001). At this concentration, outflow tract vessels constricted by 27%., Conclusion: In the porcine anterior segment culture, the dose-dependent IOP changes caused by netarsudil matched the diameter changes of distal outflow tract vessels. Hyper- and hypotensive properties of netarsudil persisted after TM removal.

Background: Annexin A3 (Anxa3) is a member of the calcium-regulated, cell membrane-binding family of annexin proteins. We previously confirmed that Anxa3 is expressed in the endothelial lineage in vertebrates and that loss of anxa3 in Xenopus laevis leads to embryonic blood vessel defects. However, the biological function of Anxa3 in mammals is completely unknown. In order to investigate Anxa3 vascular function in mammals, we generated an endothelial cell-specific Anxa3 conditional knockout mouse model (Anxa3 f/f ;Tie2-Cre)., Results: Anxa3 f/f ;Tie2-Cre mice are born at Mendelian ratios and display morphologically normal blood vessels during development. However, loss of Anxa3 leads to artery-vein (AV) misalignment characterized by atypical AV crossovers in the postnatal and adult retina., Conclusions: Anxa3 is not essential for embryonic blood vessel formation but is required for proper parallel AV alignment in the murine retina. AV crossovers associated with Anxa3 f/f ;Tie2-Cre mice are similar to AV intersections observed in patients with branch retinal vein occlusion (BRVO), although we did not observe occluded vessels. This new Anxa3 mouse model may provide a basis for understanding AV crossover formation associated with BRVO., (© 2020 Wiley Periodicals, Inc.)

In this study, we investigated the morphological features and tensile properties of the forewing costal vein of the honeybee (Apis mellifera) under fresh, dry and in vitro-time varied conditions. The costal vein is composed of an outer sub-vein and an inner vein starting from the wing base to nearly 50% of the wing span and then they are fused into one vein extending to the wing tip. Confocal laser scanning microscopy revealed that the outer sub-vein with red autofluorescence is stiffer than the inner one with green autofluorescence, and the membrane in the gap between the sub-veins exhibited a long blue-autofluorescence resilin stripe. Considering the irregular cross-sectional shape of the costal vein, cross-sections of the tested specimens after tensile failure were analysed using scanning electron microscopy, to precisely calculate their cross-sectional areas by a customized MATLAB program. The Young's modulus and tensile strength of fresh specimens were ∼4.78 GPa and ∼119.84 MPa, which are lower than those of dry specimens (∼9.08 GPa and ∼154.45 MPa). However, the tensile strain had the opposite relationship (fresh: ∼0.031, dry: ∼0.018). Thus, specimen desiccation results in increasing stiffness and brittleness. The morphological features and material properties of the costal vein taken together represent a tradeoff between both deformability and stiffness. Our study provides guidance for material selection and bionic design of the technical wings of flapping micro aerial vehicles.

Brain endothelial cells (BECs) are key constituents of the blood-brain barrier (BBB), protecting the brain from pathogens and restricting access of circulatory factors. Yet, because circulatory proteins have prominent age-related effects on adult neurogenesis, neuroinflammation, and cognitive function in mice, we wondered whether BECs receive and potentially relay signals between the blood and brain. Using single-cell RNA sequencing of hippocampal BECs, we discover that capillary BECs-compared with arterial and venous BECs-undergo the greatest transcriptional changes in normal aging, upregulating innate immunity and oxidative stress response pathways. Short-term infusions of aged plasma into young mice recapitulate key aspects of this aging transcriptome, and remarkably, infusions of young plasma into aged mice exert rejuvenation effects on the capillary transcriptome. Together, these findings suggest that the transcriptional age of BECs is exquisitely sensitive to age-related circulatory cues and pinpoint the BBB itself as a promising therapeutic target to treat brain disease., Competing Interests: Declaration of Interests The authors declare no competing interests., (Published by Elsevier Inc.)

Background: Hepatectomies promote considerable amount of blood loss and the need to administrate blood products, which are directly linked to higher morbimortality rates. The blood-conserving hepatectomy (BCH) is a modification of the selective vascular occlusion technique. It could be a surgical maneuver in order to avoid or to reduce the blood products utilization in the perioperative period., Aim: To evaluate in rats the BCH effects on the hematocrit (HT) variation, hemoglobin serum concentration (HB), and on liver regeneration., Methods: Twelve Wistar rats were divided into two groups: control (n=6) and intervention (n=6). The ones in the control group had their livers partially removed according to the Higgins and Anderson technique, while the rats in the treatment group were submitted to BCH technique. HT and HB levels were measured at day D0, D1 and D7. The rate between the liver and rat weights was calculated in D0 and D7. Liver regeneration was quantitatively and qualitatively evaluated., Results: The HT and HB levels were lower in the control group as of D1 onwards, reaching an 18% gap at D7 (p=0.01 and p=0.008, respectively); BCH resulted in the preservation of HT and HB levels to the intervention group rats. BCH did not alter liver regeneration in rats., Conclusion: The BCH led to beneficial effects over the postoperative HT and serum HB levels with no setbacks to liver regeneration. These data are the necessary proof of evidence for translational research into the surgical practice. A) Unresected liver; B) liver appearance after the partial hepatectomy (1=vena cava; 2=portal vein; 3=hepatic vein; 4=biliary drainage; 5=hepatic artery).

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease affecting mainly preterm newborns. It is characterized by unexpected onset and rapid progression with specific diagnostic signs as pneumatosis intestinalis or gas in the portal vein appearing later in the course of the disease. Therefore, we analyzed diagnostic and prognostic potential of the markers of early NEC pathogenesis, such as excessive inflammatory response (serum amyloid A (SAA)) and gut epithelium damage (intestinal and liver fatty acid-binding protein (I-FABP and L-FABP, respectively) and trefoil factor-3 (TFF-3)). We used ELISA to analyze these biomarkers in the urine of patients with suspected NEC, either spontaneous or surgery-related, or in infants without gut surgery (controls). Next, we compared their levels with the type of the disease (NEC or sepsis) and its severity. Already at the time of NEC suspicion, infants who developed NEC had significantly higher levels of all tested biomarkers than controls and higher levels of I-FABP and L-FABP than those who will later develop sepsis. Infants who will develop surgery-related NEC had higher levels of I-FABP and L-FABP than those who will develop sepsis already during the first 6 hours after the abdominal surgery. I-FABP was able to discriminate between infants who will develop NEC or sepsis and the SAA was able to discriminate between medical and surgical NEC. Moreover, the combination of TFF-3 with I-FABP and SAA could predict pneumatosis intestinalis , and the combination of I-FABP, L-FABP, and SAA could predict gas in the portal vein or long-term hospitalization and low SAA predicts early full enteral feeding. Thus, these biomarkers may be useful not only in the early, noninvasive diagnostics but also in the subsequent NEC management., Competing Interests: The authors declare that they have no conflicts of interests., (Copyright © 2020 Stepan Coufal et al.)

Central venous pressure and volume status are relevant parameters for characterization of a patient's hemodynamic condition; however, their invasive assessment is affected by various risks while non-invasive approaches provide limited and subjective indications. Here we explore the possibility of assessing venous pulse wave velocity (vPWV), a potential indicator of venous pressure changes. In eight healthy patients, pressure pulses were generated artificially in the leg veins by rapid compression of the foot, and their propagation was detected at the level of the superficial femoral vein with Doppler ultrasound. Changes in leg venous pressure were obtained by raising the trunk from the initial supine position by 30° and 60°. vPWV increased from 1.78 ± 0.06 m/s (supine) to 2.26 ± 0.19 m/s (60°) (p < 0.01) and exhibited an overall linear relationship with venous pressure. These results indicate that vPWV can be easily assessed, and is a non-invasive indicator of venous pressure changes., Competing Interests: Conflict of interest disclosure A patent application on the measurement of venous pulse wave velocity has been submitted., (Copyright © 2019 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Rapid estimates of the central venous pressure (CVP) can be helpful to administer early fluid therapy or to manage cardiac preload in intensive care units, operating rooms or emergency rooms in order to start and monitor an adequate medical therapy. Invasive CVP measurements have inherent and non-negligible complication rates as well as great expenditures. Several noninvasive methods of CVP measurements, like ultrasound-guided techniques, are available, but require trained skills and special equipment which might not be at hand in all situations. Our purpose was to evaluate the feasibility and accuracy of CVP estimates assessed upon the height of hand veins collapse (HVC) using invasively measured CVP as the gold standard. The HVC was determined by slowly lifting the patient's hand while watching the dorsal hand veins to collapse. The vertical distance from the dorsal hand to a transducer air zero port was noted and converted to mmHg. The observer was blinded to the simultaneously measured CVP values, which were categorized as low (<7 mmHg), normal (7-12 mmHg) and high (>12 mmHg). Measurements were performed in 82 patients who had a median [IQR] age of 67 [60;74]. Median CVP was 12 [8;15] mmHg and the median absolute difference between the measured HVC and CVP was 4 [2;7] mmHg. The Spearman correlation coefficient between CVP and HVC was 0.55, 95%-CI [0.35;0.69]. Overall CVP categorization was correct in 45% of the cases. HVC had a sensitivity of 92% for a low CVP with a negative predictive value of 98%. A high HVC had a sensitivity of 29% but a high specificity of 94% for a high CVP. The overall performance of observing the hand vein collapse to estimate CVP was only moderate in the intensive care setting. However, the median difference to the CVP was low and HVC identifies a low CVP with a high sensitivity and excellent negative predictive value., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The understanding of functional facial anatomy and the interplay between facial structures is crucial for safe and effective minimally invasive and cosmetic surgical procedures., Aim: In this experimental study, we investigate the hypothesis that smiling can alter the blood flow in the angular/facial vein., Materials and Methods: Twenty-six observations from 15 healthy volunteers (6 men, 9 women) with a mean age of 50.53 ± 13.27 (range: 24-66) were obtained. Doppler ultrasound imaging of the infraorbital segment of the angular vein (cranial to the zygomaticus major muscle) was performed and the venous flow was measured in a smiling and a resting, nonsmiling facial position., Results: A statistically significant change in venous blood flow was detected upon smiling: a reduction in flow from 6.12 ± 3.0 cm/s to 0.52 ± 1.3 cm/s (P = .001). After three seconds, 80.8% of the observations had a blood flow of 0.0 cm/s. Increasing age was significantly correlated with a persistent blood flow during smiling (r p  = .469; P = .016). No differences between gender and sides of the face were observed., Conclusion: The results of this experimental study reveal that smiling can significantly reduce the venous flow in the angular/facial vein. Contraction of the zygomaticus major muscle compresses the vein against the underlying maxilla. Both minimally invasive and surgical procedures that alter the SMAS, the periocular musculature or the deep midfacial fat compartments might affect angular/facial venous flow., (© 2019 Wiley Periodicals, Inc.)

The venoarteriolar reflex is a local mechanism that induces vasoconstriction during venous congestion in various tissues, including skin. This response is thought to play a critical role in minimizing capillary damage or edema resulting from overperfusion, though factors that modulate this response remain largely unknown. Here, we hypothesized that nitric oxide synthase (NOS), cyclooxygenase (COX), and Ca 2+ -activated, ATP-sensitive, and voltage-gated K + channels (K Ca , K ATP , and K V channels, respectively) modulate the venoarteriolar reflex in human skin. Cutaneous blood flow (laser-Doppler flowmetry) was monitored during a 3-min pre-occlusion baseline and following a 3-min venous occlusion of 45 mmHg, the latter maneuver was used to induce the venoarteriolar reflex. The venoarteriolar reflex was assessed at the following forearm skin sites: Experiment 1 (n = 11): 1) lactated Ringer solution (Control), 2) 10 mM N ω -nitro- L -arginine (NOS inhibitor), 3) 10 mM ketorolac (COX inhibitor), and 4) combined NOS + COX inhibition; Experiment 2 (n = 15): 1) lactated Ringer solution (Control), 2) 50 mM tetraethylammonium (K Ca channel blocker), 3) 5 mM glybenclamide (K ATP channel blocker), and 4) 10 mM 4-aminopyridine (K V channel blocker). Separate and combined NOS and COX inhibition as well as K ATP channel blocker had no effect on venoarteriolar reflex. Conversely, venoarteriolar reflex was attenuated by K Ca channel blockade (36-38%) and augmented by K V channel blockade (38-55%). We showed that K Ca and K V channels modulate the venoarteriolar reflex with minimum roles of NOS, COX, and K ATP channels in human non-glabrous forearm skin in vivo. Thus, cutaneous venoarteriolar reflex changes could reflect altered K + channel function., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The aspects of disruption of venous blood outflow from face region into skull are well-known; they can occur at any age - from neonatal to old age, however, the possible compensation mechanisms for such disorders are usually difficult to identify. A description is given of a unique case of unilateral epistaxis and a homolateral (right-sided) headache that developed much later. Examination revealed hypoplasia of the left sigmoid sinus and blood overflow of the right sigmoid sinus. After prescription of betahistine in a dose of 24 mg before bedtime and after awakening the headache and nosebleeds disappeared on the second day. The effect was persistent. The case demonstrates previously unknown compensation mechanisms for venous outflow - a retrograde outflow from the skull to the face region.

Although widely used as a preclinical model for studying cardiovascular diseases, there is a scarcity of in vivo hemodynamic measurements of the naïve murine system in multiple arterial and venous locations, from head-to-toe, and across sex and age. The purpose of this study is to quantify cardiovascular hemodynamics in mice at different locations along the vascular tree while evaluating the effects of sex and age. Male and female, adult and aged mice were anesthetized and underwent magnetic resonance imaging. Data were acquired from four co-localized vessel pairs (carotid/jugular, suprarenal and infrarenal aorta/inferior vena cava (IVC), femoral artery/vein) at normothermia (core temperature 37 ± 0.2 °C). Influences of age and sex on average velocity differ by location in arteries. Average arterial velocities, when plotted as a function of distance from the heart, decrease nearly linearly from the suprarenal aorta to the femoral artery (adult and aged males: - 0.33 ± 0.13, R 2  = 0.87; - 0.43 ± 0.10, R 2  = 0.95; adult and aged females: - 0.23 ± 0.07, R 2  = 0.91; - 0.23 ± 0.02, R 2  = 0.99). Average velocity of aged males and average volumetric flow of aged males and females tended to be larger compared to adult comparators. With cardiovascular disease as the leading cause of death and with the implications of cardiovascular hemodynamics as important biomarkers for health and disease, this work provides a foundation for sex and age comparisons in pathophysiology by collecting and analyzing hemodynamic data for the healthy murine arterial and venous system from head-to-toe, across sex and age.

This study evaluated the morphological changes of the lower limb and associated hemodynamic responses to different lower-body compression pressures (COMPs) in physically active, healthy individuals at rest. Each of the 32 participants underwent three trials with three different degrees of lower-body compression applied: "Low" (2.2±1.4 mmHg), "Medium" (12.9±3.9 mmHg), and "High" (28.8±8.3 mmHg). In each COMP, a cross-sectional area of leg muscles (CSA muscle ), subcutaneous fat (CSA fat ), superficial vessels (SupV), deep arteries (DA), and deep veins (DV) at the calf, knee, and thigh levels were measured using magnetic resonance imaging (MRI). Additionally, blood pressure (BP), heart rate (HR), cardiac output (CO), stroke volume (SV), and systemic vascular resistance (SVR) were measured using Doppler ultrasound (USCOM ® ). With High COMP, calf CSA muscle and SupV were smaller (p<0.01), whereas DA and DV were larger (p<0.05). Calf CSA fat , however, was similar among all COMPs. There were no major changes in CSA muscle and CSA fat at knee and thigh levels. CO (3.2±0.9 L/min) and SV (51.9±16.4 mL) were higher (p<0.05) only with High COMP, but other hemodynamic variables showed no significant changes across different COMPs. The High COMP at the lower limb induces leg morphological changes and increases associated hemodynamic responses of physically active healthy individuals at rest., Competing Interests: The authors declare no conflicts of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)