A Unique Collateral Artery Development Program Promotes Neonatal Heart Regeneration.

Collateral arteries are an uncommon vessel subtype that can provide alternate blood flow to preserve tissue following vascular occlusion. Some patients with heart disease develop collateral coronary arteries, and this correlates with increased survival. However, it is not known how these collaterals develop or how to stimulate them. We demonstrate that neonatal mouse hearts use a novel mechanism to build collateral arteries in response to injury. Arterial endothelial cells (ECs) migrated away from arteries along existing capillaries and reassembled into collateral arteries, which we termed "artery reassembly". Artery ECs expressed CXCR4, and following injury, capillary ECs induced its ligand, CXCL12. CXCL12 or CXCR4 deletion impaired collateral artery formation and neonatal heart regeneration. Artery reassembly was nearly absent in adults but was induced by exogenous CXCL12. Thus, understanding neonatal regenerative mechanisms can identify pathways that restore these processes in adults and identify potentially translatable therapeutic strategies for ischemic heart disease.

Detection of Topological Spin Textures via Nonlinear Magnetic Responses.

Topologically nontrivial spin textures, such as skyrmions and dislocations, display emergent electrodynamics and can be moved by spin currents over macroscopic distances. These unique properties and their nanoscale size make them excellent candidates for the development of next-generation race-track memory and unconventional computing. A major challenge for these applications and the investigation of nanoscale magnetic structures in general is the realization of suitable detection schemes. We study magnetic disclinations, dislocations, and domain walls in FeGe and reveal pronounced responses that distinguish them from the helimagnetic background. A combination of magnetic force microscopy (MFM) and micromagnetic simulations links the response to the local magnetic susceptibility, that is, characteristic changes in the spin texture driven by the MFM tip. On the basis of the findings, which we explain using nonlinear response theory, we propose a read-out scheme using superconducting microcoils, presenting an innovative approach for detecting topological spin textures and domain walls in device-relevant geometries.

Ex vivo biomechanical analysis of flexible versus rigid annuloplasty rings in mitral valves using a novel annular dilation system.

BACKGROUND: Mitral annuloplasty rings restore annular dimensions to increase leaflet coaptation, serving a fundamental component in mitral valve repair. However, biomechanical evaluations of annuloplasty rings are lacking. We aim to biomechanically analyze flexible and rigid annuloplasty rings using an ex vivo mitral annular dilation model. METHODS: Juvenile porcine mitral valves (n = 4) with intercommissural distance of 28 mm were dilated to intercommissural distances of 40 mm using a 3D-printed dilator and were sewn to an elastic mount. Fiber bragg grating sensors were anchored to native chordae to measure chordal forces. The valves were repaired using size 28 rigid and flexible annuloplasty rings in a random order. Hemodynamic data, echocardiography, and chordal force measurements were collected. RESULTS: Mitral annular dilation resulted in decreased leaflet coaptation height and increased mitral regurgitation fraction. Both the flexible and rigid annuloplasty rings effectively increased leaflet coaptation height compared to that post dilation. Rigid ring annuloplasty repair significantly decreased the mitral regurgitation fraction. Flexible annuloplasty ring repair reduced the chordal rate of change of force (7.1 ± 4.4 N/s versus 8.6 ± 5.9 N/s, p = 0.02) and peak force (0.6 ± 0.5 N versus 0.7 ± 0.6 N, p = 0.01) compared to that from post dilation. Rigid annuloplasty ring repair was associated with higher chordal rate of change of force (9.8 ± 5.8 N/s, p = 0.0001) and peak force (0.7 ± 0.5 N, p = 0.01) compared to that after flexible ring annuloplasty repair. CONCLUSIONS: Both rigid and flexible annuloplasty rings are effective in increasing mitral leaflet coaptation height. Although the rigid annuloplasty ring was associated with slightly higher chordal stress compared to that of the flexible annuloplasty ring, it was more effective in mitral regurgitation reduction. This study may help direct the design of an optimal annuloplasty ring to further improve patient outcomes.

Comprehensive Ex Vivo Comparison of 5 Clinically Used Conduit Configurations for Valve-Sparing Aortic Root Replacement Using a 3-Dimensional-Printed Heart Simulator.

BACKGROUND: Many graft configurations are clinically used for valve-sparing aortic root replacement, some specifically focused on recapitulating neosinus geometry. However, the specific impact of such neosinuses on valvular and root biomechanics and the potential influence on long-term durability are unknown. METHODS: Using a custom 3-dimenstional-printed heart simulator with porcine aortic roots (n=5), the anticommissural plication, Stanford modification, straight graft (SG), Uni-Graft, and Valsalva graft configurations were tested in series using an incomplete counterbalanced measures design, with the native root as a control, to mitigate ordering effects. Hemodynamic and videometric data were analyzed using linear models with conduit as the fixed effect of interest and valve as a fixed nuisance effect with post hoc pairwise testing using Tukey's correction. RESULTS: Hemodynamics were clinically similar between grafts and control aortic roots. Regurgitant fraction varied between grafts, with SG and Uni-Graft groups having the lowest regurgitant fractions and anticommissural plication having the highest. Root distensibility was significantly lower in SG versus both control roots and all other grafts aside from the Stanford modification (P≤0.01 for each). All grafts except SG had significantly higher cusp opening velocities versus native roots (P<0.01 for each). Relative cusp opening forces were similar between SG, Uni-Graft, and control groups, whereas anticommissural plication, Stanford modification, and Valsalva grafts had significantly higher opening forces versus controls (P<0.01). Cusp closing velocities were similar between native roots and the SG group, and were significantly lower than observed in the other conduits (P≤0.01 for each). Only SG and Uni-Graft groups experienced relative cusp closing forces approaching that of the native root, whereas relative forces were >5-fold higher in the anticommissural plication, Stanford modification, and Valsalva graft groups. CONCLUSIONS: In this ex vivo modeling system, clinically used valve-sparing aortic root replacement conduit configurations have comparable hemodynamics but differ in biomechanical performance, with the straight graft most closely recapitulating native aortic root biomechanics.

Variability in hair gadolinium concentrations among decedents who received gadolinium-based contrast agents.

This study utilized laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to quantify gadolinium in the hair of autopsy cases that had received gadolinium-based contrast agents (GBCAs) before death. Consecutive autopsy cases were reviewed for GBCA injections and subjects who received a single type of GBCA in the year before death were included. Hair samples were analyzed using LA-ICP-MS as a line scan technique and parameters were optimized to maximize instrument sensitivity, accuracy, and precision. Linear regression analyses between hair measures and gadolinium dose were executed. LA-ICP-MS analysis produced a time-resolved record of GCBA exposure, with the position of the gadolinium peak maxima along the hair shaft providing a good estimate for the day that GBCA injection occurred (R2 = 0.46; p = 0.0022); however, substantial within and between subject variation in the position of the GBCA peak was observed. Average area under the curve for gadolinium peaks in the hair samples was a better predictor of gadolinium dose (R2 = 0.41; p = 0.0046), compared to the average of peak maxima concentration. Correlation between area under the curve and dose suggests that LA-ICP-MS analysis of hair may be an effective method to evaluate gadolinium levels in subjects in vivo after exposure to GBCAs. This study demonstrates that analysis of human hair using techniques with high spatial resolution such as LA-ICP-MS has excellent potential to reveal time-dependent signatures of past exposures.

Multi-phase catheter-injectable hydrogel enables dual-stage protein-engineered cytokine release to mitigate adverse left ventricular remodeling following myocardial infarction in a small animal model and a large animal model.

Although ischemic heart disease is the leading cause of death worldwide, mainstay treatments ultimately fail because they do not adequately address disease pathophysiology. Restoring the microvascular perfusion deficit remains a significant unmet need and may be addressed via delivery of pro-angiogenic cytokines. The therapeutic effect of cytokines can be enhanced by encapsulation within hydrogels, but current hydrogels do not offer sufficient clinical translatability due to unfavorable viscoelastic mechanical behavior which directly impacts the ability for minimally-invasive catheter delivery. In this report, we examine the therapeutic implications of dual-stage cytokine release from a novel, highly shear-thinning biocompatible catheter-deliverable hydrogel. We chose to encapsulate two protein-engineered cytokines, namely dimeric fragment of hepatocyte growth factor (HGFdf) and engineered stromal cell-derived factor 1α (ESA), which target distinct disease pathways. The controlled release of HGFdf and ESA from separate phases of the hyaluronic acid-based hydrogel allows extended and pronounced beneficial effects due to the precise timing of release. We evaluated the therapeutic efficacy of this treatment strategy in a small animal model of myocardial ischemia and observed a significant benefit in biological and functional parameters. Given the encouraging results from the small animal experiment, we translated this treatment to a large animal preclinical model and observed a reduction in scar size, indicating this strategy could serve as a potential adjunct therapy for the millions of people suffering from ischemic heart disease.

Development and Ex Vivo Validation of Novel Force-Sensing Neochordae for Measuring Chordae Tendineae Tension in the Mitral Valve Apparatus Using Optical Fibers With Embedded Bragg Gratings.

Few technologies exist that can provide quantitative data on forces within the mitral valve apparatus. Marker-based strain measurements can be performed, but chordal geometry and restricted optical access are limitations. Foil-based strain sensors have been described and work well, but the sensor footprint limits the number of chordae that can be measured. We instead utilized fiber Bragg grating (FBG) sensors-optical strain gauges made of 125 µm diameter silica fibers-to overcome some limitations of previous methods of measuring chordae tendineae forces. Using FBG sensors, we created a force-sensing neochord (FSN) that mimics the natural shape and movement of native chordae. FBG sensors reflect a specific wavelength of light depending on the spatial period of gratings. When force is applied, the gratings move relative to one another, shifting the wavelength of reflected light. This shift is directly proportional to force applied. The FBG sensors were housed in a protective sheath fashioned from a 0.025 in. flat coil, and attached to the chordae using polytetrafluoroethylene suture. The function of the force-sensing neochordae was validated in a three-dimensional (3D)-printed left heart simulator, which demonstrated that FBG sensors provide highly sensitive force measurements of mitral valve chordae at a temporal resolution of 1000 Hz. As ventricular pressures increased, such as in hypertension, chordae forces also increased. Overall, FBG sensors are a viable, durable, and high-fidelity sensing technology that can be effectively used to measure mitral valve chordae forces and overcome some limitations of other such technologies.

Rapid Self-Assembly of Bioengineered Cardiovascular Bypass Grafts From Scaffold-Stabilized, Tubular Bilevel Cell Sheets.

BACKGROUND: Cardiovascular bypass grafting is an essential treatment for complex cases of atherosclerotic disease. Because the availability of autologous arterial and venous conduits is patient-limited, self-assembled cell-only grafts have been developed to serve as functional conduits with off-the-shelf availability. The unacceptably long production time required to generate these conduits, however, currently limits their clinical utility. Here, we introduce a novel technique to significantly accelerate the production process of self-assembled engineered vascular conduits. METHODS: Human aortic smooth muscle cells and skin fibroblasts were used to construct bilevel cell sheets. Cell sheets were wrapped around a 22.5-gauge Angiocath needle to form tubular vessel constructs. A thin, flexible membrane of clinically approved biodegradable tissue glue (Dermabond Advanced) served as a temporary, external scaffold, allowing immediate perfusion and endothelialization of the vessel construct in a bioreactor. Subsequently, the matured vascular conduits were used as femoral artery interposition grafts in rats (n=20). Burst pressure, vasoreactivity, flow dynamics, perfusion, graft patency, and histological structure were assessed. RESULTS: Compared with engineered vascular conduits formed without external stabilization, glue membrane-stabilized conduits reached maturity in the bioreactor in one-fifth the time. After only 2 weeks of perfusion, the matured conduits exhibited flow dynamics similar to that of control arteries, as well as physiological responses to vasoconstricting and vasodilating drugs. The matured conduits had burst pressures exceeding 500 mm Hg and had sufficient mechanical stability for surgical anastomoses. The patency rate of implanted conduits at 8 weeks was 100%, with flow rate and hind-limb perfusion similar to those of sham controls. Grafts explanted after 8 weeks showed a histological structure resembling that of typical arteries, including intima, media, adventitia, and internal and external elastic membrane layers. CONCLUSIONS: Our technique reduces the production time of self-assembled, cell sheet-derived engineered vascular conduits to 2 weeks, thereby permitting their use as bypass grafts within the clinical time window for elective cardiovascular surgery. Furthermore, our method uses only clinically approved materials and can be adapted to various cell sources, simplifying the path toward future clinical translation.

An ultra low-cost smartphone device for in-situ monitoring of acute organophosphorus poisoning for agricultural workers.

In this work, we present an ultra-low-cost smartphone device for in situ quantification of OP poisoning severity. The performance of the lens-less smartphone spectrum apparatus (LeSSA) is evaluated using standard human Interleukin-6 (IL-6) immunoassay kits. Upon dose-response curve fitting, LeSSA demonstrates an accuracy of 99.5%. The limit of detection (LOD) of LeSSA was evaluated through comparison of 6.4 pg/ml with standard laboratory grade UV-vis spectrophotometer at 5.5 pg/ml. Evaluating the capacity of LeSSA in spike solution by combining plasma cholinesterase (PChE) and human plasma shows consistency at agreement of 97.6% between LeSSA and the laboratory instrument. For application demonstration, the activity of PChE for 24 agricultural workers' plasma samples was measured with LeSSA, showing exceptional agreement (r2 = 0.92) with the laboratory instrument reference. In addition to near laboratory grade accuracy, the total manufacturing cost of LeSSA is only $20 USD highlighting it's affordability. With LeSSA, clinicians can evaluate OP poisoning severity without the need to transport patient samples to facilities at far distances. Utilizing LeSSA, immediate results can be used for administration of appropriate treatment.

Tissue-engineered smooth muscle cell and endothelial progenitor cell bi-level cell sheets prevent progression of cardiac dysfunction, microvascular dysfunction, and interstitial fibrosis in a rodent model of type 1 diabetes-induced cardiomyopathy.

BACKGROUND: Diabetes mellitus is a risk factor for coronary artery disease and diabetic cardiomyopathy, and adversely impacts outcomes following coronary artery bypass grafting. Current treatments focus on macro-revascularization and neglect the microvascular disease typical of diabetes mellitus-induced cardiomyopathy (DMCM). We hypothesized that engineered smooth muscle cell (SMC)-endothelial progenitor cell (EPC) bi-level cell sheets could improve ventricular dysfunction in DMCM. METHODS: Primary mesenchymal stem cells (MSCs) and EPCs were isolated from the bone marrow of Wistar rats, and MSCs were differentiated into SMCs by culturing on a fibronectin-coated dish. SMCs topped with EPCs were detached from a temperature-responsive culture dish to create an SMC-EPC bi-level cell sheet. A DMCM model was induced by intraperitoneal streptozotocin injection. Four weeks after induction, rats were randomized into 3 groups: control (no DMCM induction), untreated DMCM, and treated DMCM (cell sheet transplant covering the anterior surface of the left ventricle). RESULTS: SMC-EPC cell sheet therapy preserved cardiac function and halted adverse ventricular remodeling, as demonstrated by echocardiography and cardiac magnetic resonance imaging at 8 weeks after DMCM induction. Myocardial contrast echocardiography demonstrated that myocardial perfusion and microvascular function were preserved in the treatment group compared with untreated animals. Histological analysis demonstrated decreased interstitial fibrosis and increased microvascular density in the SMC-EPC cell sheet-treated group. CONCLUSIONS: Treatment of DMCM with tissue-engineered SMC-EPC bi-level cell sheets prevented cardiac dysfunction and microvascular disease associated with DMCM. This multi-lineage cellular therapy is a novel, translatable approach to improve microvascular disease and prevent heart failure in diabetic patients.

Anticoagulant rodenticide toxicity in six dogs presenting for ocular disease.

OBJECTIVE: To describe cases of suspected anticoagulant rodenticide toxicity manifesting with predominantly ocular signs. MATERIALS AND METHODS: Six canine cases that presented to veterinary referral hospitals for ocular abnormalities and were diagnosed with suspected or confirmed anticoagulant rodenticide ingestion were reviewed for commonalities in presentation and outcome. RESULTS: Five dogs had unilateral ocular signs and one dog had bilateral manifestations. Signs included subconjunctival hemorrhage, exophthalmos, and commonly orbital pain without other significant physical examination findings. Prothrombin time was measured in 5 of 6 dogs and was prolonged in all. Partial thromboplastin time was measured in 4 of 6 dogs and was prolonged in all. Complete blood cell count and serum chemistry profiles demonstrated mild, if any, abnormalities. Five dogs had known anticoagulant rodenticide exposure, and rodenticide ingestion was suspected in 1 additional case based on clinical signs, clinical pathologic abnormalities, and response to treatment. Five of 6 cases were hospitalized overnight for plasma transfusions along with oral or injectable vitamin K1 , and all dogs were treated with oral vitamin K1 for 30 days. All dogs experienced complete resolution of clinical signs within 6 weeks of initiating treatment. CONCLUSIONS: Anticoagulant rodenticide toxicity can present with predominantly ocular manifestations. Rodenticide ingestion should be considered in dogs with unilateral or bilateral subconjunctival hemorrhage, exophthalmos, and orbital pain.

Nitro-PAH exposures of occupationally-exposed traffic workers and associated urinary 1-nitropyrene metabolite concentrations.

The assessment of occupational exposure to diesel exhaust (DE) is important from an epidemiological perspective. Urinary biomarkers of exposure have been proposed as a novel approach for measuring exposure to DE. In this study, we measured the concentrations of two urinary metabolites of 1-nitropyrene (1NP), a nitrated polycyclic aromatic hydrocarbon that has been suggested as a molecular marker of diesel particulate matter. These two metabolites, 6-hydroxy-1-nitropyrene and 8-hydroxy-1-nitropyrene, were determined in urine samples (10mL) from a small group of workers who were occupationally-exposed to vehicle exhaust in Trujillo, Peru, before and after their workshifts. Workshift exposures to 1NP, as well as PM2.5, 2-nitropyrene and 2-nitrofluoranthene, were also measured. Exposures to 1NP were similar in all studied workers, averaging 105±57.9pg/m3 (±standard deviation). Median urinary concentrations of the average of the pre- and post-exposure samples for 6-hydroxy-1-nitropyrene and 8-hydroxy-1-nitropyrene, were found to be 3.9 and 2.3pgmetabolite/mg creatinine, respectively in the group of occupationally-exposed subjects (n=17) studied. A direct relationship between workshift exposure to 1NP and urinary 1NP metabolites concentrations was not observed. However, the 1NP exposures and the creatinine-corrected urinary concentrations of the hydroxynitropyrene metabolites in these Peruvian traffic workers were similar to occupationally-exposed taxi drivers in Shenyang, China, and were higher than biomarker levels in office workers from Trujillo without occupational exposure to vehicle exhaust. This study provides further evidence that urinary metabolites of 1NP are associated with exposure to DE and may serve as a useful exposure biomarker.

Neighborhood-Scale Spatial Models of Diesel Exhaust Concentration Profile Using 1-Nitropyrene and Other Nitroarenes.

With emerging evidence that diesel exhaust exposure poses distinct risks to human health, the need for fine-scale models of diesel exhaust pollutants is growing. We modeled the spatial distribution of several nitrated polycyclic aromatic hydrocarbons (NPAHs) to identify fine-scale gradients in diesel exhaust pollution in two Seattle, WA neighborhoods. Our modeling approach fused land-use regression, meteorological dispersion modeling, and pollutant monitoring from both fixed and mobile platforms. We applied these modeling techniques to concentrations of 1-nitropyrene (1-NP), a highly specific diesel exhaust marker, at the neighborhood scale. We developed models of two additional nitroarenes present in secondary organic aerosol: 2-nitropyrene and 2-nitrofluoranthene. Summer predictors of 1-NP, including distance to railroad, truck emissions, and mobile black carbon measurements, showed a greater specificity to diesel sources than predictors of other NPAHs. Winter sampling results did not yield stable models, likely due to regional mixing of pollutants in turbulent weather conditions. The model of summer 1-NP had an R(2) of 0.87 and cross-validated R(2) of 0.73. The synthesis of high-density sampling and hybrid modeling was successful in predicting diesel exhaust pollution at a very fine scale and identifying clear gradients in NPAH concentrations within urban neighborhoods.

Blood α-synuclein in agricultural pesticide handlers in central Washington State.

Epidemiologic studies suggest that occupational exposure to pesticides might increase Parkinson disease risk. Some pesticides, such as the organophosphorus insecticide chlorpyrifos, appear to increase the expression of α-synuclein, a protein critically involved in Parkinson disease. Therefore, we assessed total blood cell α-synuclein in 90 specimens from 63 agricultural pesticide handlers, mainly Hispanic men from central Washington State, who participated in the state's cholinesterase monitoring program in 2007-2010. Additionally, in age-adjusted linear regression models for repeated measures, we assessed whether α-synuclein levels were associated with butyrylcholinesterase-chlorpyrifos adducts or cholinesterase inhibition measured in peripheral blood, or with self-reported pesticide exposure or paraoxonase (PON1) genotype. There was no evidence by any of those indicators that exposure to chlorpyrifos was associated with greater blood α-synuclein. We observed somewhat greater α-synuclein with the PON1-108T (lower paraoxonase enzyme) allele, and with ≥ 10 h of exposure to cholinesterase inhibiting insecticides in the preceding 30 days, but neither of these associations followed a clear dose-response pattern. These results suggest that selected genetic and environmental factors may affect α-synuclein blood levels. However, longitudinal studies with larger numbers of pesticide handlers will be required to confirm and elucidate the possible associations observed in this exploratory cross-sectional study.

Evaluation of Orthotrichum lyellii moss as a biomonitor of diesel exhaust.

Exhaust from diesel combustion engines is an important contributor to urban air pollution and poses significant risk to human health. Diesel exhaust contains a chemical class known as nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) and is enriched in 1-nitropyrene (1-NP), which has the potential to serve as a marker of diesel exhaust. The isomeric nitro-PAHs 2-nitropyrene (2-NP) and 2-nitrofluoranthene (2-NFL) are secondary pollutants arising from photochemical oxidation of pyrene and fluoranthene, respectively. Like other important air toxics, there is not extensive monitoring of nitro-PAHs, leading to gaps in knowledge about relative exposures and urban hotspots. Epiphytic moss absorbs water, nutrients, and pollutants from the atmosphere and may hold potential as an effective biomonitor for nitro-PAHs. In this study we investigate the suitability of Orthotrichum lyellii as a biomonitor of diesel exhaust by analyzing samples of the moss for 1-NP, 2-NP, and 2-NFL in the Seattle, WA metropolitan area. Samples were collected from rural parks, urban parks, residential, and commercial/industrial areas (N = 22 locations) and exhibited increasing concentrations across these land types. Sampling and laboratory method performance varied by nitro-PAH, but was generally good. We observed moderate to moderately strong correlation between 1-NP and select geographic variables, including summer normalized difference vegetation index (NDVI) within 250 m (r = -0.88, R2 = 0.77), percent impervious surface within 50 m (r = 0.83, R2 = 0.70), percent high development land use within 500 m (r = 0.77, R2 = 0.60), and distance to nearest secondary and connecting road (r = -0.75, R2 = 0.56). The relationships between 2-NP and 2-NFL and the geographic variables were generally weaker. Our results suggest O. lyellii is a promising biomonitor of diesel exhaust, specifically for 1-NP. To our knowledge this pilot study is the first to evaluate using moss concentrations of nitro-PAHs as biomonitors of diesel exhaust.

Uncommon presentations of type A quadricuspid aortic valve in the Septuagenarian.

BACKGROUND: Quadricuspid aortic valve (QAV) is a rare congenital anomaly characterized by the presence of four cusps instead of the usual three. It is estimated to occur in less than 0.05% of the population, with Type A (four equal-sized leaflets) accounting for roughly 30% of QAV subtypes. Based on limited clinical series, the usual presentation is progressive aortic valve regurgitation (AR) with symptoms occurring in the fourth to sixth decade of life. Severe aortic valve stenosis (AS) and acute AR are very uncommon. CASE PRESENTATION: We describe two cases of Type A QAV in patients who remained asymptomatic until their seventies with very uncommon presentations: one with severe AS and one with acute, severe AR and flail leaflet. In Case A, a 72-year-old patient with history of moderate AS presents to clinic with progressive exertional dyspnea. During work-up for transcatheter vs. surgical replacement pre-operative computed tomography angiogram (CTA) reveals a quadricuspid aortic valve with severe AS, and the patient undergoes surgical aortic valve replacement. Pre-discharge transthoracic echocardiography (TTE) shows good prosthetic valve function with no gradient or regurgitation. In Case B, a 76-year-old patient is intubated upon arrival to the hospital for acute desaturation, found to have wide open AR on catheterization, and transferred for emergent intervention. Intraoperative TEE reveals QAV with flail leaflet and severe AR. Repair is considered but deferred ultimately due to emergent nature. Post-operative TTE demonstrates good prosthetic valve function with no regurgitation and normal biventricular function. CONCLUSIONS: QAV can present as progressive severe AS and acute AR, with symptoms first occurring in the seventh decade of life. The optimal treatment for QAV remains uncertain. Although aortic valve repair or transcatheter option may be feasible in some patients, aortic valve replacement remains a tenable option.

Olfactory tract/bulb metal concentration in Manganese-exposed mineworkers.

BACKGROUND: Manganese (Mn) is an essential micronutrient as well as a well-established neurotoxicant. Occupational and environmental exposures may bypass homeostatic regulation and lead to increased systemic Mn levels. Translocation of ultrafine ambient airborne particles via nasal neuronal pathway to olfactory bulb and tract may be an important pathway by which Mn enters the central nervous system. OBJECTIVE: To measure olfactory tract/bulb tissue metal concentrations in Mn-exposed and non-exposed mineworkers. METHODS: Using inductively coupled plasma-mass spectrometry (ICP-MS), we measured and compared tissue metal concentrations in unilateral olfactory tracts/bulbs of 24 Mn-exposed and 17 non-exposed South African mineworkers. We used linear regression to investigate the association between cumulative Mn exposures and olfactory tract/bulb Mn concentration. RESULTS: The difference in mean olfactory tract/bulb Mn concentrations between Mn-exposed and non-Mn exposed mineworkers was 0.16 µg/g (95% CI -0.11, 0.42); but decreased to 0.09 µg/g (95% CI 0.004, 0.18) after exclusion of one influential observation. Olfactory tract/bulb metal concentration and cumulative Mn exposure suggested there may be a positive association; for each mg Mn/m3-year there was a 0.05 µg/g (95% CI 0.01, 0.08) greater olfactory tract/bulb Mn concentration overall, but -0.003 (95% CI -0.02, 0.02) when excluding the three influential observations. Recency of Mn exposure was not associated with olfactory tract/bulb Mn concentration. CONCLUSIONS: Our findings suggest that Mn-exposed mineworkers might have higher olfactory tract/bulb tissue Mn concentrations than non-Mn exposed mineworkers, and that concentrations might depend more on cumulative dose than recency of exposure.

An ultra-low field SQUID magnetometer for measuring antiferromagnetic and weakly remanent magnetic materials at low temperatures.

A novel setup for measuring magnetic fields of antiferromagnets (i.e., quadrupolar or higher-order magnetic fields) and generally weakly remanent magnetic materials is presented. The setup features a highly sensitive superconducting quantum interference device magnetometer with a magnetic field resolution of ∼ 10 fT and non-electric temperature control of the sample space for a temperature range of 1.5-65 K with a non-electric sample movement drive and optical position encoding. To minimize magnetic susceptibility effects, the setup components are degaussed and realized with plastic materials in sample proximity. Running the setup in magnetically shielded rooms allows for a well-defined ultra-low magnetic background field well below 150 nT in situ. The setup enables studies of inherently weak magnetic materials, which cannot be measured with high field susceptibility setups, optical methods, or neutron scattering techniques, giving new opportunities for the research on, e.g., spin-spiral multiferroics, skyrmion materials, and spin ices.

Trimmed central venous catheters do not increase endothelial injury in an ovine model.

INTRODUCTION: Central venous catheters (CVCs) are often trimmed during heart transplantation and pediatric cardiac surgery. However, the risk of endothelial injury caused by the cut tip of the CVC has not been evaluated. We hypothesized that there is no difference in the degree of endothelial injury associated with trimmed CVCs versus standard untrimmed CVCs. METHODS: In four adult male sheep, the left external jugular vein was exposed in three segments, one designated for an untouched control group, one for the trimmed CVC group, and one for the untrimmed CVC group. Trimmed and untrimmed CVC tips were rotated circumferentially within their respective segments to abrade the lumen of the vein. The vein samples were explanted, and two representative sections from each sample were analyzed using hematoxylin and eosin (H&E) staining, as well as with immunohistochemistry against CD31, von Willebrand factor (vWF), endothelial nitric oxide synthase (eNOS), and caveolin. Higher immunohistochemical stain distributions and intensities are associated with normal health and function of the venous endothelium. Data are presented as counts with percentages or as means with standard error. RESULTS: H&E staining revealed no evidence of endothelial injury in 6/8 (75%) samples from the untouched control group, and no injury in 4/8 (50%) samples from both the trimmed and untrimmed CVC groups (p = 0.504). In all remaining samples from each group, only mild endothelial injury was observed. Immunohistochemical analysis comparing trimmed CVCs versus untrimmed CVCs revealed no difference in the percentage of endothelial cells staining positive for CD31 (57.5% ± 7.2% vs 55.0% ± 9.2%, p = 0.982), vWF (73.8% ± 8.0% vs 62.5% ± 9.6%, p = 0.579), eNOS (66.3% ± 4.2% vs 63.8% ± 7.5%, p = 0.962), and caveolin (53.8% ± 5.0% vs 51.3% ± 4.4%, p = 0.922). There were no significant differences between the groups in the distributions of stain intensity for CD31, vWF, eNOS, and caveolin. CONCLUSION: Trimmed CVCs do not increase endothelial injury compared to standard untrimmed CVCs.

Microfluidic encapsulation of photosynthetic cyanobacteria in hydrogel microparticles augments oxygen delivery to rescue ischemic myocardium.

Cardiovascular disease, primarily caused by coronary artery disease, is the leading cause of death in the United States. While standard clinical interventions have improved patient outcomes, mortality rates associated with eventual heart failure still represent a clinical challenge. Macrorevascularization techniques inadequately address the microvascular perfusion deficits that persist beyond primary and secondary interventions. In this work, we investigate a photosynthetic oxygen delivery system that rescues the myocardium following acute ischemia. Using a simple microfluidic system, we encapsulated Synechococcus elongatus into alginate hydrogel microparticles (HMPs), which photosynthetically deliver oxygen to ischemic tissue in the absence of blood flow. We demonstrate that HMPs improve the viability of S. elongatus during the injection process and allow for simple oxygen diffusion. Adult male Wistar rats (n = 45) underwent sham surgery, acute ischemia reperfusion surgery, or a chronic ischemia reperfusion surgery, followed by injection of phosphate buffered saline (PBS), S. elongatus suspended in PBS, HMPs, or S. elongatus encapsulated in HMPs. Treatment with S. elongatus-HMPs mitigated cellular apoptosis and improved left ventricular function. Thus, delivery of S. elongatus encapsulated in HMPs improves clinical translation by utilizing a minimally invasive delivery platform that improves S. elongatus viability and enhances the therapeutic benefit of a novel photosynthetic system for the treatment of myocardial ischemia.