MHC class I-specific antibody binding to nonhematopoietic cells drives complement activation to induce transfusion-related acute lung injury in mice

Transfusion-related acute lung injury (TRALI), a form of noncardiogenic pulmonary edema that develops during or within 6 h after a blood transfusion, is the most frequent cause of transfusion-associated death in the United States. Because development of TRALI is associated with donor antibodies (Abs) reactive with recipient major histocompatibility complex (MHC), a mouse model has been studied in which TRALI-like disease is caused by injecting mice with anti-MHC class I monoclonal Ab (mAb). Previous publications with this model have concluded that disease is caused by FcR-dependent activation of neutrophils and platelets, with production of reactive oxygen species that damage pulmonary vascular endothelium. In this study, we confirm the role of reactive oxygen species in the pathogenesis of this mouse model of TRALI and show ultrastructural evidence of pulmonary vascular injury within 5 min of anti-MHC class I mAb injection. However, we demonstrate that disease induction in this model involves macrophages rather than neutrophils or platelets, activation of complement and production of C5a rather than activation of FcγRI, FcγRIII, or FcγRIV, and binding of anti-MHC class I mAb to non-BM-derived cells such as pulmonary vascular endothelium. These observations have important implications for the prevention and treatment of TRALI.     

Novel Biomarkers in Acute Heart Failure

Heart failure goes beyond mechanical dysfunction and involves an interplay of multiple pathophysiologic mechanisms, including inflammation, tissue remodeling, neurohormonal and endocrine signaling, and interactions with the renal and nervous systems. This article highlights some novel biomarkers that may aid in diagnosis, treatment, and prognosis of acute heart failure, specifically focusing on ST2, endoglin, galectin-3, cystatin C, neutrophil gelatinase–associated lipocalin, midregional pro-adrenomedullin, chromogranin A, adiponectin, resistin, and leptin and their emerging clinical roles.     

Coronary artery bypass surgery provokes Alzheimer's disease-like changes in the cerebrospinal fluid

Several biomarkers are used in confirming the diagnosis of cognitive disorders. This study evaluates whether the level of these markers after heart surgery correlates with the development of cognitive dysfunction, which is a frequent complication of cardiac interventions. Concentrations of amyloid-β peptide, tau, and S100β in the cerebro-spinal fluid were assessed, as well as cognitive functions were evaluated before and after coronary artery bypass grafting, utilizing immuno-assays and psychometric tests, respectively. A drastic rise in the level of S100β was observed one week after the surgery, a mark of a severe generalized cerebral injury. The level of amyloid-β peptide significantly decreased, whereas the concentration of tau markedly increased six months postoperatively. Gradual cognitive decline was also present. These findings clearly demonstrate post-surgical cognitive impairment associated with changes in biomarkers similar to that seen in Alzheimer's disease, suggesting a unifying pathognomic factor between the two disorders. A holistic approach to coronary heart disease and Alzheimer's type dementia is proposed.     

Precise control of end‐tidal carbon dioxide and oxygen improves BOLD and ASL cerebrovascular reactivity measures

In‐depth investigation of cerebrovascular blood flow and MR mechanisms underlying the blood oxygenation level dependent signal requires precise manipulation of the arterial partial pressure of carbon dioxide and oxygen, measured by their noninvasive surrogates, the end‐tidal values. The traditional methodology consists of administering a fixed fractional concentration of inspired CO₂, but this causes a variable ventilatory response across subjects, resulting in different values of end‐tidal partial pressures of CO₂ and O₂. In this study, we investigated whether fine control of these end‐tidal partial pressures would improve stability and predictability of blood oxygenation level dependent and arterial spin labeling signals for studying cerebrovascular reactivity. In 11 healthy volunteers, we compared the MR signals generated by the traditional fixed fractional concentration of inspired CO₂ method to those of an automated feed‐forward system, a simpler, safer, and more compact alternative to dynamic end‐tidal forcing systems, designed to target constant end‐tidal partial pressures of CO₂ and O₂. We found that near square‐wave changes in end‐tidal partial pressure of CO₂ of 5, 7.5, and 10 mm Hg (±1.01 mm Hg within two to three breaths) and constrained changes in the end‐tidal partial pressure of O₂ (<10 mm Hg) induced cerebral vascular reactivity measurements with faster transitions, together with improved stability and gradation, than those achieved with the traditional fixed fractional concentration of inspired CO₂ method. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Evidences for calcium-dependent inactivation of calcium current at the frog motor nerve terminal

Assessment of calcium-dependent inactivation of calcium current in nerve terminals is not feasible due to technical reasons. Perineural measurement of calcium-flow, however, might be utilized as indirect means to evaluate synaptic currents. Using perineural recording from frog neuromuscular junction, supra-threshold stimuli applied to motor nerve in paired-pulse manner with varying inter-pulse intervals (5-50 ms) are demonstrated in this study to cause paired-pulse depression (PPD) of Ca(2+)-current. PPD of Ca(2+)-flow was reduced at lower extracellular Ca(2+) concentrations, in BAPTA-AM and EGTA-AM treated preparations and after replacing extracellular Ca(2+) with Sr(2+). Using perineural measurement of calcium current as an indirect model to investigate synaptic ionic activity, our findings demonstrate that PPD may be attributed to calcium-dependent inactivation of Ca(2+)-current, which may serve as negative feedback in response to massive Ca(2+) entry to motor nerve terminals. A putative sensor of Ca(2+)-current is also proposed in this study.     

Biodegradable Polymer Nanosheets Incorporated with Zn-Containing Nanoparticles for Biomedical Applications

So far, poly(L-lactic acid), PLLA nanosheets proved to be promising for wound healing. Such biodegradable materials are easy to prepare, bio-friendly, cost-effective, simple to apply and were shown to protect burn wounds and facilitate their healing. At the same time, certain metal ions are known to be essential for wound healing, which is why this study was motivated by the idea of incorporating PLLA nanosheets with Zn²⁺ ion containing nanoparticles. Upon being applied on wound, such polymer nanosheets should release Zn²⁺ ions, which is expected to improve wound healing. The work thus focused on preparing PLLA nanosheets embedded with several kinds of Zn-containing nanoparticles, their characterization and ion-release behavior. ZnCl₂ and ZnO nanoparticles were chosen because of their different solubility in water, with the intention to see the dynamics of their Zn²⁺ ion release in liquid medium with pH around 7.4. Interestingly, the prepared PLLA nanosheets demonstrated quit similar ion release rates, reaching the maximum concentration after about 10 h. This finding implies that such polymer materials can be promising as they are expected to release ions within several hours after their application on skin.     

Preparation and Properties of Iron Nanoparticle-Based Macroporous Scaffolds for Biodegradable Implants

Fe-based scaffolds are of particular interest in the technology of biodegradable implants due to their high mechanical properties and biocompatibility. In the present work, using an electroexplosive Fe nanopowder and NaCl particles 100–200 µm in size as a porogen, scaffolds with a porosity of about 70 ± 0.8% were obtained. The effect of the sintering temperature on the structure, composition, and mechanical characteristics of the scaffolds was considered. The optimum parameters of the sintering process were determined, allowing us to obtain samples characterized by plastic deformation and a yield strength of up to 16.2 MPa. The degradation of the scaffolds sintered at 1000 and 1100 °C in 0.9 wt.% NaCl solution for 28 days resulted in a decrease in their strength by 23% and 17%, respectively.     

Hardening of Additive Manufactured 316L Stainless Steel by Using Bimodal Powder Containing Nanoscale Fraction

The particle size distribution significantly affects the material properties of the additively manufactured parts. In this work, the influence of bimodal powder containing nano- and micro-scale particles on microstructure and materials properties is studied. Moreover, to study the effect of the protective atmosphere, the test samples were additively manufactured from 316L stainless steel powder in argon and nitrogen. The samples fabricated from the bimodal powder demonstrate a finer subgrain structure, regardless of protective atmospheres and an increase in the Vickers microhardness, which is in accordance with the Hall-Petch relation. The porosity analysis revealed the deterioration in the quality of as-built parts due to the poor powder flowability. The surface roughness of fabricated samples was the same regardless of the powder feedstock materials used and protective atmospheres. The results suggest that the improvement of mechanical properties is achieved by adding a nano-dispersed fraction, which dramatically increases the total surface area, thereby contributing to the nitrogen absorption by the material.     

Contemporary Use of Venoarterial Extracorporeal Membrane Oxygenation: Insights from the Multicenter RESCUE Registry

BackgroundVenoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used as a life-saving therapy for patients with cardiovascular collapse, but identifying patients unlikely to benefit remains a challenge.Methods and ResultsWe created the RESCUE registry, a retrospective, observational registry of adult patients treated with VA-ECMO between January 2007 and June 2017 at 3 high-volume centers (Columbia University, Duke University, and Washington University) to describe short-term patient outcomes. In 723 patients treated with VA-ECMO, the most common indications for deployment were postcardiotomy shock (31%), cardiomyopathy (including acute heart failure) (26%), and myocardial infarction (17%). Patients frequently suffered in-hospital complications, including acute renal dysfunction (45%), major bleeding (41%), and infection (33%). Only 40% of patients (n = 290) survived to discharge, with a minority receiving durable cardiac support (left ventricular assist device [n = 48] or heart transplantation [n = 7]). Multivariable regression analysis identified risk factors for mortality on ECMO as older age (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.12–1.42) and female sex (OR, 1.44; 95% CI, 1.02–2.02) and risk factors for mortality after decannulation as higher body mass index (OR 1.17; 95% CI, 1.01-1.35) and major bleeding while on ECMO support (OR, 1.92; 95% CI, 1.23–2.99).ConclusionsDespite contemporary care at high-volume centers, patients treated with VA-ECMO continue to have significant in-hospital morbidity and mortality. The optimization of outcomes will require refinements in patient selection and improvement of care delivery.