Leaky Valves Research Articles

Obesity‐Induced Lymphatic Valve Dysfunction

A two‐way connection between obesity and lymphatic dysfunction has now been established. Clinical studies have demonstrated that obesity significantly increases the risk for developing secondary lymphedema. Using animal‐models, obesity has been linked to different aspects of lymphatic dysfunction including impaired contractility, flow‐mediated responses, and fluid transport, as well as increased permeability, and impaired dendritic cell migration among others. Dysfunction of lymphatic valves is a main form of lymphatic dysfunction, known to result in severe edematous phenotypes; however, the extent of lymphatic valve deficiency in secondary lymphedema, including obesity‐induced lymphedema, remains unknown. Therefore, the aim of the present study was to determine whether obesity resulted in lymphatic valve dysfunction. We quantitatively assessed and compared valve function in isolated popliteal and mesenteric collecting lymphatic vessels from control and diet‐induced obese mice. Feeding a western diet (N=7) for 14 weeks induced obesity, resulting in significant gain of body weight, i.e., 18.8±1.4 g, versus 9.7±0.7 g for mice fed a control diet (N=6). Obese mice displayed significantly higher non‐fasted blood glucose concentration when compared to controls. The function of lymphatic valves in popliteal lymphatics was not affected by diet‐induced obesity; however, obesity resulted in significant back‐leak of pressure in mesenteric lymphatic valves (0.1±0.1 versus 0.7±0.1 cmH2O for control (n=11) and obese (n=16) groups respectively). Dysfunctional, leaky valves from obese animals required significantly higher adverse pressure to trigger valve closure (i.e., 5.5±1.6 cmH2O, versus 0.9±0.3 cmH2O for controls, when upstream pressure was maintained at 0.5 cmH2O). In obese animals, valve dysfunction in mesenteric lymphatics was associated with structural and mechanical modifications including shortening of valve leaflets, enlargement of the lymphatic vasculature, and increased cross‐sectional distensibility. This is the first study that reports on quantitative assessment of lymphatic valve function in an animal model of obesity, and the first to link obesity with lymphatic valve dysfunction. Finally, utilizing a newly developed method for the isolation and culturing of primary lymphatic endothelial cells (LECs) from collecting vessels, our current and future experiments seek to assess and understand functional modifications to LECs induced by obesity in‐vitro. Specifically, using high‐speed confocal microscopy, mouse lines carrying genetically encoded Ca2+ indicators (i.e., Cdh5‐GCaMP8 and acta2‐RCaMP), and lymphatic cellular co‐cultures, we aim to determine whether obesity results in intracellular calcium dysregulation in LECs, and/or abnormal crosstalk between LECs and lymphatic muscle cells.

Lymphatic Valve Dysfunction in Western Diet-Fed Mice: New Insights Into Obesity-Induced Lymphedema.

A two-way connection between obesity and lymphatic dysfunction has now been established. Clinical studies have demonstrated that obesity significantly increases the risk for developing secondary lymphedema. Using animal-models, obesity and metabolic syndrome have been linked to different aspects of lymphatic structural abnormalities and lymphatic dysfunction, including impaired contractility, impaired flow-mediated responses, impaired fluid transport, as well as increased permeability, and abnormal dendritic cell migration among others. Dysfunction of lymphatic valves is a main form of lymphatic dysfunction, known to result in severe edematous phenotypes; however, the extent of lymphatic valve deficiency in secondary lymphedema, including obesity-induced lymphedema, remains unknown. Therefore, the aims of the present study were 1) to determine whether western diet-induced obesity results in lymphatic valve dysfunction, and 2) to determine whether lymphatic valve dysfunction in western diet-induced obesity results from the diet itself, or as a consequence of the metabolic alterations induced by the diet. First, we quantitatively assessed and compared valve function in isolated popliteal and mesenteric collecting lymphatic vessels from control and western diet-induced obese C57BL/6J (WT) mice. Feeding a western diet for 14 weeks induced obesity and elevated plasma glucose and cholesterol levels when compared to controls. The function of lymphatic valves in popliteal lymphatics was not affected by diet-induced obesity; however, significant back-leak of pressure was observed in mesenteric lymphatic valves. Dysfunctional, leaky valves from obese animals also required significantly higher adverse pressure to trigger valve closure. Importantly, when subjected to treatment with a western diet, globally deficient PAI-1 mice were significantly protected against metabolic dysfunction and displayed fully functional, competent mesenteric lymphatic valves. In conclusion, our findings show for the first time that, in association with the metabolic alterations induced by the western diet, lymphatic valve dysfunction can be a critical component of obesity-induced lymphedema.

In Vitro Hemodynamic Evaluation of Right Ventricle-Pulmonary Artery Continuity Reconstruction Through a Trileaflet Expanded Polytetrafluoroethylene Valved Conduit.

Percutaneous pulmonary valve implantation is a technique to treat narrowed pulmonary valves or leaky pulmonary valves in congenital heart disease. This technique provides a promising strategy to reduce surgical risk. In clinical cases, due to stent size restrictions, commercial valve stents are sometimes unsuitable for children or certain patients. Hence, handmade pulmonary valved conduits prove useful because a customized size can be obtained for valve replacement. We propose a meta-learning-based intelligent model to train an estimator (including two sub-estimators) to determine optimal trileaflet parameters for customized trileaflet valve reconstruction. The purpose of this study was to investigate the hemodynamic and functional consequences of the novel design by employing a mock circulation system. We recorded the diastolic valve leakage and calculated the pulmonary regurgitation, regurgitation fraction, and ejection efficiency in a pulsatile setting. The prosthetic leaflet behavior was assessed using an endoscope camera and the pressure drops through valves were measured. All the in vitro parameters indicated that the expanded polytetrafluoroethylene (ePTFE) valved conduits were not inferior to commercial mechanical or tissue valve conduits and could decrease the regurgitation volume and increase the efficiency. Compatible early clinical outcomes were also identified between ePTFE valved conduits and other valved conduits used for right ventricular outflow tract reconstruction. The ePTFE valved conduits could be implanted in relatively small patients. An in vitro experimental study provided evidence that a handmade ePTFE valved conduit could be an attractive alternative to other commercialized valved conduits used for right ventricle-pulmonary artery continuity reconstruction.

Defective lymphatic valve development and chylothorax in mice with a lymphatic-specific deletion of Connexin43

Lymphatic valves (LVs) are cusped luminal structures that permit the movement of lymph in only one direction and are therefore critical for proper lymphatic vessel function. Congenital valve aplasia or agenesis can, in some cases, be a direct cause of lymphatic disease. Knowledge about the molecular mechanisms operating during the development and maintenance of LVs may thus aid in the establishment of novel therapeutic approaches to treat lymphatic disorders. In this study, we examined the role of Connexin43 (Cx43), a gap junction protein expressed in lymphatic endothelial cells (LECs), during valve development. Mouse embryos with a null mutation in Cx43 (Gja1) were previously shown to completely lack mesenteric LVs at embryonic day 18. However, interpreting the phenotype of Cx43-/- mice was complicated by the fact that global deletion of Cx43 causes perinatal death due to heart defects during embryogenesis. We have now generated a mouse model (Cx43∆LEC) with a lymphatic-specific ablation of Cx43 and show that the absence of Cx43 in LECs causes a delay (rather than a complete block) in LV initiation, an increase in immature valves with incomplete leaflet elongation, a reduction in the total number of valves, and altered lymphatic capillary patterning. The physiological consequences of these lymphatic changes were leaky valves, insufficient lymph transport and reflux, and a high incidence of lethal chylothorax. These results demonstrate that the expression of Cx43 is specifically required in LECs for normal development of LVs.

Two step silicon microfluidics for capillary valve applications

In this publication, we report on a robust and scalable process flow for fabrication of valves, compatible with other microfluidic components using silicon microfabrication techniques. The valves require an abrupt change in both the depth and width of a rectangular microchannel for proper functioning. We report on the process that allow for a very sharp interface between the two areas of the channel. A non-sharp interface will results in leaky valves. We show the variation in silicon etch depth as function of feature size. For small features (3–10)μm there is roughly a 50 percent increase in etch depth compared to 40μm features, while features above 40 μm show minimal differences in depth. For the formation of valves, this provides important design rules allowing one to make structures with precise dimensions. Initial characterization, demonstrating the functionality of the fabricated valves is also be presented.

Cardiology patient page. Prevention of acute rheumatic fever and rheumatic heart disease.

Acute rheumatic fever (ARF) is primarily the result of a bacterial infection with potentially serious consequences for the heart. ARF develops from contact with a specific bacterium called Group A Streptococcus (GAS).1,2 After exposure, the body generates antibodies to help destroy the bacteria. However, because of close structural similarity between certain parts of the bacterial cell wall and heart tissue, these antibodies may also act against the person’s own heart valves (which separate the different chambers of the heart). This leads to valve damage in the form of narrowed ( stenotic ) or leaky ( regurgitant ) valves. Over time, there is progressive damage (rheumatic heart disease, RHD) that may lead to heart failure, stroke, infection of the valves (infective endocarditis), and death.2 This disease has been almost eradicated in Western countries, but remains a major health problem in developing countries and among indigenous populations in wealthy countries. RHD is related to overcrowding, inadequate hygiene, poor access to healthcare, and low awareness. Recent estimates suggest that disability related to RHD alone equals more than a quarter of all cancers put together. Globally, RHD remains the leading cause of heart failure in children and young adults, accounting for at least 250 000 deaths annually. ARF usually occurs a few weeks after sore throat caused by GAS and may affect the joints, skin, brain, and heart. Involvement of the heart (occurring in more than half of the cases) results in the most severe manifestations, both acute and long term (Table 1). Although the first ARF episode can sometimes …

Leaky Vessels, Valves, and Veins: How Lymphangiogenesis Genes are the Valve Regulators in Veins

Leaky Vessels, Valves, and Veins: How Lymphangiogenesis Genes are the Valve Regulators in Veins

Leaky Valves Lead to Sheath Recall

Leaky Valves Lead to Sheath Recall

Gadze Modernism

Gadže Modernism Janet Lyon (bio) In April 1908, not long before his career-ending mental breakdown, Arthurs Symons published a notice in the Journal of the Gypsy Lore Society titled "In Praise of Gypsies."1 Though brief, the essay is freighted with the exoticism characterizing most gypsophilia at the time—indeed, characterizing most ethnographic endeavors of the early modernist period. The occasion for Symons's essay was the impending passage of the Moveable Dwellings Bill, the aim of which was to register, regulate, and provide for the sanitary inspection of the vans and tents of British Gypsies and Travellers, and to mandate the education of their children.2 But Symons's indignation in the face of this proposed legislation—which, he claims, will "shuffle (the 'Gypsies') right off the very earth to which they have the universal human right" (298)—is largely disconnected from the actual social conditions of the Romani populations in England and Wales ("PG," 298). Instead it springs mainly from Symons's investment in the fictional romantic figure of the "Gypsy," a "natural man" whose instinctual drive for freedom leads him away from civilization's gatekeepers along a secret and infinitely receding road limning the outer reaches of modernity. Symons repeats all of the nineteenth-century tropes of orientalism and race, mysticism and ahistoricity: "Gypsies" are "changeless: the world has not power over them. They live by rote and by faith and by tradition which is part of their blood" ("PG," 295); they are "prophets," "our only link with the East, with mystery, with magic"; they are possessed of the "lawlessness, the abandonment, the natural physical grace in form and gesture, of animals; only a stealthy and wary something in their eyes makes them human" ("PG," 296). They are the atavistic [End Page 517] trace of the rural, pre-modern world, and they will remain when "cities and nations have vanished, as the dust vanishes before the wind." 3 The robust, though elusive figure of the "Gypsy" is an elixir for the desiccated spirit of the West, at least in the eyes of this fading avatar of Symbolism; even the well-known "Gypsy faults" of "secrecy," "lying" and "thieving" can be lessons in anti-modern resistance for the perceptive man who will but recognize them ("PG," 297-98). Thus Symons replicates one vector of the multivalent figure of the gadže (non-Romani) creation called the "Gypsy." This is the celebrated Romani "Gypsy," an emblem of natural liberty, unencumbered mobility, communal loyalty and harmony, admirably impervious to manipulation by the state and everywhere subverting the disciplinarity of evolving modern institutions. But of course there were other more dominant and historically entrenched vectors of representation, lingering on from pre-romantic policies of xenophobia and mid-empire racial sciences, heightened by the coalescence of wage labor after the major phase of the industrial revolution, and disseminated in the parallel discourses of national character and social control of the nineteenth century. According to these, the perceived freedoms of the "Gypsy" were in fact manifestations of congenital lawlessness, habitual restlessness, a perversely arrested sense of domesticity, and—perhaps most dangerously—a resolute unwillingness to settle and perform "honest" wage labor. The fabled insularity of "Gypsy" communities was proof of a radical alterity that might be anti-statist or anti-Christian or just plain criminal in origin; in any case it was seen to shelter illiteracy and uncleanliness, and perpetuate itinerant poverty. However divergent the affective force of these positions might have been, both the celebratory and suspicious views of the "Gypsy" shared some important assumptions, as they were largely flip sides of the same ideological coin: the British "Gypsy" (in spite of 500 years of Gypsy-Traveller populations in England) was foreign, or at least fundamentally not-English; it was also, for all of its proud self-sufficiency, notably—even recidivistically—primitive. For both champions and detractors, the figure of the "Gypsy" seemed to reveal something about the leaky valves of modernity: living in the midst of "progress" (in a country where the institutions of modernity had been established especially early) the "Gypsy" somehow—actively—avoided modernity's ineluctable telos. Such a figure could be of great value both to...

Leaky Valves in Littoral Sediment Budgets: Loss of Nearshore Sand to Deep Offshore Zones via Chutes in Barrier Reef Systems, Southeast Coast of Florida, USA

The decrease in longshore sediment volumes from north to south, calculated for littoral cells between inlets, indicates significant loss from the littoral drift system along the Florida east coast or localized deposition. The decrease in littoral drift volume from about 490,000 m3 of sediment over a distance of about 550 km (average diminution rate of about 890 m3 km−1) was traditionally accounted for in terms of alongshore deposition and some unknown degree of speculated offshore transport. With the application of laser airborne depth sounding (LADS) technology to bathymetric survey in southeast Florida (2001–2003), recognition of detailed bottom topography became possible for the first time. Significant in this regard was the bathymetric display of macro- and mesoscale morphological features that showed areal continuity of sandy bottoms and the prominent but disjunctive occurrence of relict barrier coral reef tracts that line the shelf edge. Identification of gaps in the line of barrier reefs showed pathways of cross-shore sediment transport from the inner shelf to offshore beyond the shelf edge. Diabathic sediment transport through these reef gaps robs the littoral sediment package by allowing the chuting of sediments during high energy events or when the backreef flats over fill with sand. The reef gaps are thus leaky valves where littoral sediments are periodically chuted offshore and lost from the littoral drift system.

Tagging Out Fire Hydrants Can Prevent Injuries

A hydrant requires a visible notice not only when it is broken but also if it is open and unattended. Verbal notification alone is insufficient. This article describes how a large Midwestern water utility learned this the hard way when two employees were seriously hurt after a firefighter shut down a hydrant that had been opened to relieve pressure while water department employees worked on leaky valves in an excavated pit nearby.

Endoluminal Abdominal Aortic Aneurysm Repair Complicated by Intracardiac Guidewire Placement and Massive Transfusion

Endoluminal Abdominal Aortic Aneurysm Repair Complicated by Intracardiac Guidewire Placement and Massive Transfusion

Protection Against Dust by Respirators.

This article is a brief review of the mechanism of action of fibrous filters and of the performance of respirators; it neglects many of the complications discussed in longer and more detailed articles. An expression is given for the pressure drop across a filter in terms of fibre diameter and filtration velocity. The particle capture mechanisms of interception and diffusional deposition are introduced and the way in which filtration efficiency varies with particle size is discussed. Filters with fibres of small diameter are shown to be the most efficient, but their use can cause problems. Electrically charged materials are widely used in respirators because of their high efficiency and low pressure drop. Types of material, their means of charging, and their method of action are described. An account is given of respirator leakage, the protection factor, and of the way that these may vary in a period of use. The leakage of air and particles through face seal leaks and leaky valves is discussed. The frequent discrepancy in the protection given by respirators in the workplace, on the one hand, and that suggested by laboratory measurements, on the other, is reviewed, and the article ends with an account of the combined effect of aerosol penetration through a filter and through a leak.

THE BULLETIN OF THE NORTH AMERICAN SOCIETY OF PHLEBOLOGY

The treatment of varicose veins as taught within the specialty of phlebology consists of the best combinations of sclerotherapy and surgery after a thorough evaluation by physical examination and Doppler ultrasound, as well as other techniques. Although patients can experience some relief of symptoms by external compression hosiery, only treatment that closes up leaky valves will stop the progression of disease. Sclerotherapy is a safe, well-accepted, non-investigational, highly effective method to treat abnormally enlarged veins. Surgical procedures may be necessary to supplement sclerotherapy in certain anatomic sites. Varicose veins cause patients to experience pain, lose time from work, and can ultimately lead to permanent disability. Our healthcare system must provide the most high quality cost effective care for these patients. By keeping costs down as compared with full-scale surgical procedures, the approach of sclerotherapy or sclerotherapy with outpatient surgery, performed by properly trained physicians, provides a means to accomplish this. Medical necessity criteria allow exclusion of payments for patients seeking treatment purely for cosmetic needs.