Immediate major dynamic changes in the T- and NK-cell subset composition after cardiac transplantation.

Early kinetics of lymphocyte subsets involved in tolerance and rejection following heart transplantation (HTx) are barely defined. Here, we aimed to delineate the early alloimmune response immediately after HTx. Therefore, blood samples from 23 heart-transplanted patients were collected before (pre-), immediately (T0), 24 hours (T24), and 3 weeks (3 wks) after HTx. Immunophenotyping was performed using flow cytometry. A significant increase was detected for terminally differentiated (TEMRA) CD4+ or CD8+ T cells and CD56dim CD16+ NK cells immediately after HTx linked to a decrease in naïve CD8+ and CM CD4+ T as well as CD56bright CD16- NK cells, returning to baseline levels at T24. More detailed analyses revealed increased CD69+ CD25- and diminished CD69- CD25- CD4+ or CD8+ T-cell proportions at T0 associated with decreasing S1PR1 expression. Passenger T and NK cells were found at low frequencies only in several patients at T0 and did not correlate with lymphocyte alterations. Collectively, these results suggest an immediate, transient shift toward memory T and NK cells following HTx. Opposite migratory properties of naïve versus memory T and NK cells occurring in the early phase after HTx could underlie these observations and may impinge on the development of allo-specific immune responses.

Meta-analysis contrasting freshwater biodiversity in forests and oil palm plantations with and without riparian buffers.

The expansion of oil palm plantations has led to land-use change and deforestation in the tropics, which has affected biodiversity. Although the impacts of the crop on terrestrial biodiversity have been extensively reviewed, its effects on freshwater biodiversity remain relatively unexplored. We reviewed the research assessing the impacts of forest-to-oil palm conversion on freshwater biota and the mitigating effect of riparian buffers on these impacts. We searched for studies comparing taxa richness, species abundance, and community composition of macroinvertebrates, amphibians, and fish in streams in forests (primary and disturbed) and oil palm plantations with and without riparian buffers. Then, we conducted a meta-analysis to quantify the overall effect of the land-use change on the 3 taxonomic groups. Twenty-nine studies fulfilled the inclusion criteria. On average, plantations lacking buffers hosted 44% and 19% fewer stream taxa than primary and disturbed forests, respectively. Stream taxa on plantations with buffers were 24% lower than in primary forest and did not differ significantly from disturbed forest. In contrast, stream community composition differed between forests and plantations regardless of the presence of riparian buffers. These differences were attributed to agrochemical use and altered environmental conditions in the plantations, including temperature changes, worsened water conditions, microhabitat loss, and food and shelter depletion. On aggregate, abundance did not differ significantly among land uses because increases in generalist species offset the population decline of vulnerable forest specialists in the plantation. Our results reveal significant impacts of forest-to-oil palm conversion on freshwater biota, particularly taxa richness and composition (but not aggregate abundance). Although preserving riparian buffers in the plantations can mitigate the loss of various aquatic species, it cannot conserve primary forest communities. Therefore, safeguarding primary forests from the oil palm expansion is crucial, and further research is needed to address riparian buffers as a promising mitigation strategy in agricultural areas.

Metaanálisis contrastando la biodiversidad de agua dulce en los bosques y las plantaciones de palma de aceite con o sin bosques ribereños Resumen La expansión de las plantaciones de palma de aceite ha derivado en cambios en el uso de suelo y deforestación en los trópicos, afectando a la biodiversidad. Existe una revisión extensa del impacto de este cultivo sobre la biodiversidad terrestre, pero sus efectos sobre la biodiversidad de agua dulce todavía no están muy documentados. Revisamos las investigaciones que han evaluado el impacto de la conversión de bosque a plantación de palma de aceite sobre la biota de agua dulce y el efecto mitigante que tienen los bosques ribereños sobre este impacto. Buscamos estudios que compararan la riqueza de taxones, abundancia de especies y composición comunitaria de los macroinvertebrados, anfibios y peces en los riachuelos de los bosques (primarios y perturbados) y los sembradíos de palma de aceite con y sin bosques ribereños. Después realizamos un metaanálisis para cuantificar el efecto del cambio de uso de suelo en los tres grupos taxonómicos. Veintinueve estudios cumplieron con el criterio de inclusión. En promedio, las plantaciones carentes de bosques ribereños albergaron 44% y 19% menos taxones que los bosques primarios y perturbados. Los taxones en los sembradíos con bosques ribereños fueron 24% menos que en el bosque primario y no difirieron significativamente del bosque perturbado. Como contraste, la composición comunitaria del riachuelo difirió entre los bosques y los sembradíos sin importar la presencia de los bosques ribereños. Atribuimos estas diferencias al uso de agroquímicos y las condiciones ambientales alteradas en las plantaciones, incluidas los cambios térmicos, condiciones hidrológicas alteradas, pérdida de microhábitats y reducción de alimentos y refugios. En general, la abundancia no difirió significativamente entre los usos de suelo porque el incremento de especies generalistas en las plantaciones contrarresta la declinación poblacional de los especialistas de bosque vulnerables. Nuestros resultados revelan un impacto significativo de la conversión de bosque a plantación sobre la biota de agua dulce, particularmente la riqueza de taxones y la composición (pero no la abundancia agregada). Aunque mantener los bosques ribereños en las plantaciones puede mitigar la pérdida de varias especies acuáticas, no puede conservar las comunidades del bosque primario. Por lo tanto, es crucial salvaguardar los bosques primarios de la expansión del aceite de palma, además de que se necesitan más investigaciones para abordar los bosques ribereños como una estrategia prometedora de mitigación en las áreas agrícolas.

Outcomes after SynCardia® temporary total artificial heart implantation: A 20-year single-center experience in 196 patients.

BACKGROUND: The SynCardia® temporary total artificial heart (TAH) serves as a mechanical circulatory support device for patients suffering from irreversible biventricular failure. METHODS: This retrospective study analyzed 196 consecutive patients who underwent TAH implantation at our center from 2001 to 2021. We assessed survival rates and all-cause mortality during TAH support, including survival post-heart transplantation. RESULTS: The median age of patients was 55 years, with 88% being male. The primary diagnoses included cardiomyopathy (43.9%), acute myocardial infarction (26.5%), and postcardiotomy heart failure (15.5%). At implantation, 87.2% of patients were classified as INTERMACS Profile 1. The median duration of support was 96 days (IQR: 23-227). Survival rates at 1, 6, and 12 months were 72%, 41%, and 34%, respectively. Postoperative rethoracotomy was necessary in 44.4% of patients; 39.3% experienced neurological events and 24.6% developed gastrointestinal bleeding. Overall, 64.8% of patients died while on support, primarily due to multiple organ failure (55.9%). Factors such as older age, higher bilirubin levels, postcardiotomy and specific underlying diagnoses were independent predictors of mortality during TAH support. On a positive note, 35.2% of patients underwent successful heart transplants, with 1-, 5-, and 10-year posttransplant survival rates of 65%, 58%, and 51%, respectively. CONCLUSIONS: While high mortality rates persist among patients with biventricular failure, the SynCardia® TAH offers a viable interim solution for critically ill patients, particularly those who can be successfully bridged to heart transplantation.

Is there a Covalent Au(I)-Au(I) Bond in the trans-(AuX)2 (X = F, Cl, Br, I) Structure? A Post-Hartree-Fock and Density Functional Theory Study.

We present an exhaustive exploration of the driving forces dominating the interaction between gold atoms in the trans-(AuX)2, where X is a halogen ligand. This work provides insights into the nature of the gold-gold contact in the trans-(AuX)2. The geometries and energies were calculated at the MP2, CCSD(T), and DFT-D3(BJ) (B3LYP, PBE, and TPSS) levels of theory. The results show a short Au-Au distance, typical of a covalent bond, but with a weak interaction energy associated with noncovalent interactions. It is established that the physical contributions from polarization and the electronic correlation forces are the most relevant at the post-Hartree-Fock level of theory. Also, the electrostatic term is attractive but with low contribution. Finally, the Wiberg indices and NBO analysis exposed a small covalent character between the gold atoms, revealing that this contribution is insufficient to explain the stability of the dimers. It is concluded that a sum of contributions makes it possible to establish an attraction between the gold atoms in the dimers studied beyond a classical aurophilic interaction.

Late-spring frost risk between 1959 and 2017 decreased in North America but increased in Europe and Asia.

Late-spring frosts (LSFs) affect the performance of plants and animals across the world's temperate and boreal zones, but despite their ecological and economic impact on agriculture and forestry, the geographic distribution and evolutionary impact of these frost events are poorly understood. Here, we analyze LSFs between 1959 and 2017 and the resistance strategies of Northern Hemisphere woody species to infer trees' adaptations for minimizing frost damage to their leaves and to forecast forest vulnerability under the ongoing changes in frost frequencies. Trait values on leaf-out and leaf-freezing resistance come from up to 1,500 temperate and boreal woody species cultivated in common gardens. We find that areas in which LSFs are common, such as eastern North America, harbor tree species with cautious (late-leafing) leaf-out strategies. Areas in which LSFs used to be unlikely, such as broad-leaved forests and shrublands in Europe and Asia, instead harbor opportunistic tree species (quickly reacting to warming air temperatures). LSFs in the latter regions are currently increasing, and given species' innate resistance strategies, we estimate that ∼35% of the European and ∼26% of the Asian temperate forest area, but only ∼10% of the North American, will experience increasing late-frost damage in the future. Our findings reveal region-specific changes in the spring-frost risk that can inform decision-making in land management, forestry, agriculture, and insurance policy.

Heart transplantation across preformed donor-specific antibody barriers using a perioperative desensitization protocol.

Heart transplantation across preformed donor-specific HLA-antibody barriers is associated with impaired short- and long-term survival. Therefore, in recipients with preformed anti-HLA antibodies, waiting for crossmatch-negative donors is standard practice. As an alternative strategy, recipients with preformed anti-HLA donor specific antibodies have been managed at our institutions with a perioperative desensitization regimen. A retrospective analysis was performed comparing heart transplant recipients with preformed donor-specific HLA-antibodies to recipients without donor-specific antibodies. Recipients with a positive virtual crossmatch received a perioperative desensitization protocol including tocilizumab intraoperatively, plasma exchange and rituximab followed by a six-month course of IgGAM. Among the 117 heart-transplanted patients, 19 (16%) patients underwent perioperative desensitization, and the remaining 98 (84%) patients did not. Cold ischemic time, posttransplant extracorporeal life support for primary graft dysfunction, and intensive care unit stay time did not differ between groups. At 1-year follow-up, freedom from pulsed steroid therapy for presumed rejection and biopsy-confirmed acute cellular or humoral rejection did not differ between groups. One-year survival amounted to 94.7% in the treated patients and 81.4% in the control group. Therefore, heart transplantation in sensitized recipients undergoing a perioperative desensitization appears safe with comparable postoperative outcomes as patients with a negative crossmatch.

Identification of distinct secretory patterns and their regulatory networks of ischemia versus reperfusion phases in clinical heart transplantation.

BACKGROUND: Ischemia/reperfusion injury (IRI) is associated with inflammatory responses contributing to the development of primary graft dysfunction (PGD) and rejection. Here, we investigated the pathophysiology of IRI and the early phase after heart transplantation (HTx) regarding its cytokine/chemokine and endothelial networks. METHODS: Using multiplex technology, we assessed protein concentrations in plasma samples of HTx recipients (n = 11) pre-, postoperatively, 24 h and 3 weeks after HTx. The same proteins were quantified in organ storage solutions at the end of heart storage (n = 10). Unsupervised cluster, principal component analysis (PCA), K-nearest neighbor (KNN) network classifier analysis, ANOVA and Spearman correlation analyses were performed to identify specific patterns for IRI and individual kinetics of important soluble factors in HTx. RESULTS: Unique patterns of soluble factors were identified in plasma of HTx patients. KNN analysis defined IL-10, IL-6, sIL-6Rα, IL-1RA, IL-16, sVEGFR-1, IGFBP-1, HGF and sHer-2 as strongest signals directly post-Tx declining 24 hrs after HTx. By contrast, MIF, osteopontin (OPN), sVCAM-1 and sICAM-1, IGFBP-1, SCGF-ß, HGF were highly enriched in organ storage solutions, reflecting distinct ischemic (storage solution) vs. reperfusion (plasma) signatures. CONCLUSIONS: We identified specific inflammatory signatures for ischemic vs. reperfusion phases of HTx, associated with pro- as well as anti-inflammatory and endothelial biomarker candidates for IRI. These signatures might help to identify potential danger factors and their networks at both the ex situ (ischemic) as well as the reperfusion phase in the recipient after implantation.

A yeast-based in vivo assay system for analyzing efflux of sugars mediated by glucose and xylose transporters.

Sugar transporter research focuses on the sugar uptake into cells. Under certain physiological conditions, however, the intracellular accumulation and secretion of carbohydrates (efflux) are relevant processes in many cell types. Currently, no cell-based system is available for specifically investigating glucose efflux. Therefore, we designed a system based on a hexose transporter-deficient Saccharomyces cerevisiae strain, in which the disaccharide maltose is provided as a donor of intracellular glucose. By deleting the hexokinase genes, we prevented the metabolization of glucose, and thereby achieved the accumulation of growth-inhibitory glucose levels inside the cells. When a permease mediating glucose efflux is expressed in this system, the inhibitory effect is relieved proportionally to the capacity of the introduced transporter. The assay is thereby suitable for screening of transporters and quantitative analyses of their glucose efflux capacities. Moreover, by simultaneous provision of intracellular glucose and extracellular xylose, we investigated how each sugar influences the transport of the other one from the opposite side of the membrane. Thereby, we could show that the xylose transporter variant Gal2N376F is insensitive not only to extracellular but also to intracellular glucose. Considering the importance of sugar transporters in biotechnology, the assay could facilitate new developments in a variety of applications.

Time-dependent density functional theory studies of the optical and electronic properties of the [M25(MPA)18]- (M = Au, Ag, MPA = SCH2CH2COOH) clusters.

Electronic absorption and emission spectra of [M25(MPA)18]- (M = Au, Ag; MPA = SCH2CH2COOH) clusters have been recorded for energies below 5 eV at the time-dependent density functional theory (TDDFT) level using B3LYP and TPSSh functionals and compared to the calculated ones using the computationally inexpensive simplified TDDFT (sTDDFT) approach. The results show a qualitative agreement between the TDDFT and sTDDFT approaches used here, which were also in line with the experimental and theoretical spectra previously reported. However, the sTDDFT calculations were several orders of magnitude faster than those obtained by TDDFT. Our results support that sTDDFT provides an excellent balance between accuracy and low computational cost, becoming a suitable approach for studying the absorption and emission spectra of noble-metal clusters of sizes that would be unaffordable by the traditional TDDFT methods. The main peaks of the experimental absorption spectrum of [Au25(MPA)18]- have been previously assigned, whereas [Ag25(MPA)18]- has not been synthesised. However, its absorption spectrum resulted in having similar features to the experimental spectrum of [Ag25(GSH)18]- (GSH = glutathione), used to validate our results. The emission spectra, which to date have not been reported either from experimental or theoretical means, were simulated by using the molecular structure of the first excited triplet state (T1). The emission spectra were obtained by comparing them to those of [M25(GSH)18]- since no experimental luminescence spectra have been reported for [M25(MPA)18]-. The calculations suggest that [Ag25(SR)18]- (SR = thiolate) clusters have a weak luminescence band in the NIR region. Finally, solvent shifts were found to be minor, whereas the absorption bands seem to be significantly redshifted in solid-state materials.

The HeartWare Ventricular Assist Device (HVAD): A Single Institutional 10-Year Experience.

OBJECTIVES: The aim of this study was to analyze our 10-year experience with the HVAD in a real-world scenario in a high-volume German heart center. METHODS: We retrospectively analyzed outcomes of adults (≥18 years) with terminal heart failure (HF), who underwent HVAD implantation for durable LVAD therapy in our center between October 2009 and March 2020. Primary and secondary end points were all-cause death after implantation and LVAD-associated complications, respectively. We focused the distinct analyses on risk profiles at the time of implantation and implant strategies, i.e., bridge-to-transplant (BTT) or destination therapy (DT). RESULTS: A total of 510 patients were included, with 229 and 281 individuals in Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) level 1 (45%) and 2 to 4, respectively. Median follow-up was 26 months (IQR: 5-54 months). Overall survival at 1, 3, and 5 years after HVAD implantation was 66% (95% CI; 61.7-70%), 49.4% (95% CI; 44.9-53.8%), and 37.4% (95% CI; 32.8-42%), not censored for LVAD exchange, LVAD explantation, or heart transplantation. INTERMACS level 1 and peri-operative temporary right heart assistance were independent risk factors for survival. Survival was best in BTT patients undergoing heart transplantation at any time during follow-up. The INTERMACS level at time of HVAD implantation did not affect survival after heart transplantation. Freedom from the combined end point of any device-associated severe complication and death was 44.5% (95% CI; 40-48.8%) at 1-year after implantation. CONCLUSION: The HVAD is a reliable pump for durable mechanical circulatory support even in high-risk patients. Still, heart transplantation outperforms durable MCS therapy for a superior long-term survival.

Unraveling the Role of the Tyrosine Tetrad from the Binding Site of the Epigenetic Writer MLL3 in the Catalytic Mechanism and Methylation Multiplicity.

MLL3, also known as KMT2C, is a lysine mono-methyltransferase in charge of the writing of an epigenetic mark on lysine 4 from histone 3. The catalytic site of MLL3 is composed of four tyrosines, namely, Y44, Y69, Y128, and Y130. Tyrosine residues are highly conserved among lysine methyltransferases' catalytic sites, although their complete function is still unclear. The exploration of how modifications on these residues from the enzymatic machinery impact the enzymatic activity of MLL3 could shed light transversally into the inner functioning of enzymes with similar characteristics. Through the use of QMMM calculations, we focus on the effect of the mutation of each tyrosine from the catalytic site on the enzymatic activity and the product specificity in the current study. While we found that the mutations of Y44 and Y128 by phenylalanine inactivated the enzyme, the mutation of Y128 by alanine reactivated the enzymatic activity of MLL3. Moreover, according to our models, the Y128A mutant was even found to be capable of di- and tri-methylate lysine 4 from histone 3, what would represent a gain of function mutation, and could be responsible for the development of diseases. Finally, we were able to establish the inactivation mechanism, which involved the use of Y130 as a water occlusion structure, whose conformation, once perturbed by its mutation or Y128 mutant, allows the access of water molecules that sequester the electron pair from lysine 4 avoiding its methylation process and, thus, increasing the barrier height.

Glucose-induced internalization of the S. cerevisiae galactose permease Gal2 is dependent on phosphorylation and ubiquitination of its aminoterminal cytoplasmic tail.

The hexose permease Gal2 of Saccharomyces cerevisiae is expressed only in the presence of its physiological substrate galactose. Glucose tightly represses the GAL2 gene and also induces the clearance of the transporter from the plasma membrane by ubiquitination and subsequent degradation in the vacuole. Although many factors involved in this process, especially those responsible for the upstream signaling, have been elucidated, the mechanisms by which Gal2 is specifically targeted by the ubiquitination machinery have remained elusive. Here, we show that ubiquitination occurs within the N-terminal cytoplasmic tail and that the arrestin-like proteins Bul1 and Rod1 are likely acting as adaptors for docking of the ubiquitin E3-ligase Rsp5. We further demonstrate that phosphorylation on multiple residues within the tail is indispensable for the internalization and possibly represents a primary signal that might trigger the recruitment of arrestins to the transporter. In addition to these new fundamental insights, we describe Gal2 mutants with improved stability in the presence of glucose, which should prove valuable for engineering yeast strains utilizing complex carbohydrate mixtures present in hydrolysates of lignocellulosic or pectin-rich biomass.

Secondary aortic valve replacement in continuous flow left ventricular assist device therapy.

The purpose of the study was to investigate the outcome of secondary surgical aortic valve replacement (sSAVR) in patients with severe aortic regurgitation (AR) in the context of ventricular assist device (VAD) therapy. From 2009 to 2020, 792 patients underwent cf-LVAD implantation [HVAD (Medtronic, USA), n = 585, and HM 3 (Abbott, USA), n = 207]. All cf-LVAD patients with severe AR requiring secondary AVR were enrolled in this study. A total of six patients (median, 40 years, IQR; 34-61 years, 50% male) underwent secondary surgical aortic valve replacement (sSAVR) after cf-LVAD implantation. Median time of previous LVAD support was 26 months (IQR: 21-29 months). Two patients required additional tricuspid valve repair (TVR) and one patient underwent SAVR after failed TAVR. Four patients needed temporary right ventricular assist device (RVAD) with a median of 30 days (IQR; 29-33 days). Three patients were bridged to urgent heart transplantation due to persevering right heart failure, whereas two destination therapy (DT) candidates survived without any associated complications. An additional DT patient died of pneumonia 1 month after sSAVR. Secondary surgical aortic valve replacement in ongoing LVAD patients is an advanced procedure for a complex cohort. In our series, sSAVR was safely performed and effective, but involved a high-risk for subsequent right heart failure, requiring urgent heart transplantation. In LVAD patients with severe AR requiring treatment where TAVR is not feasible, sSAVR can be evaluated as salvage option for bridge to transplant patients or selected destination therapy candidates.

Patients with ventricular assist device and cerebral entrapment-Supporting skullcap reimplantation.

Effects of cranioplasty (CP) and skullcap reimplantation after decompressive craniectomy (DC) for cerebral hemorrhage or malignant brain infarction in patients with left ventricular assist device (LVAD) support as bridge to transplantation has not been surveyed yet. The aim of this study was to evaluate outcome and management after CP when aiming for transplantation. Data were collected from our prospective institutional database including all patients undergoing LVAD implantation between 2010 and 2019. Six patients needed CP procedures and were included. Our analysis focused on postoperative outcome, survival, and facilitation of heart transplantation. Study endpoints included also all-cause mortality. From a total of 1010 LVAD implantations during analysis period in our center, six bridge-to-transplantation LVAD patients [median age at LVAD implantation: 32.5 years (IQR: 24.8-39.5 years); four male, HVAD, n = 3; HM II, n = 1; HM 3, n = 2] underwent CP with imminent entrapment secondary to cerebral hemorrhage or malignant infarction. Primary heart failure etiology was myocarditis (n = 2), dilated (n = 2), or ischemic (n = 2). Median INTERMACS class was 1.5 (IQR; 1.0-2.8). Median time on LVAD support to DC procedure was 33 months (IQR: 16-48 months). The indication for DC was intraparenchymal hemorrhage (n = 4), subdural hematoma (n = 1), and malignant middle cerebral artery infarction (n = 1). After a median time of 4 months (IQR: 3.3-4.0 months, range; 2.0-10 months) post DC procedure, CP was subsequently performed without profound neurologic disabilities in all patients. After median time of 26 months (IQR: 21-42 months) follow-up, three patients successfully received heart transplantation, one patient could undergo LVAD explantation for myocardial recovery, and the remaining two patients are still on the list awaiting heart transplantation. CP procedure with skullcap reimplantation is feasible and can be safely performed in LVAD patients, which subsequently may even be eligible for heart transplantation with beneficial prognosis.

Identification of characteristics, risk factors, and predictors of recurrent LVAD thrombosis: conditions in HeartWare devices.

BACKGROUND: Redictors of repetitive left-ventricular assist device (LVAD)-thrombosis have not been studied yet. METHODS: We identified predictors of recurrent LVAD thrombosis in HeartWare (HVAD) patients in a long-term study from 2010 until 2020. We included all patients with two or more thrombolysis treatments for repetitive HVAD thrombosis and effectiveness of thrombolytic therapy was defined as freedom from stroke, death, another HVAD thrombosis, or surgical device exchange within 30 days after the event. Study endpoints also include all-cause mortality and heart transplantation. RESULTS: A total of 534 HVAD implantations have been screened, and 73 patients (13.7%) developed first HVAD thrombosis after a median of 10 months (IQR; 6-21 months). 46 of these patients had effective thrombolysis in 71.7% (n = 33/46). After a median of 14 months (IQR 4-32 months) follow-up, 17 patients (51.5%) had developed a second HVAD thrombosis and all were treated with t-PA therapy again, resulting in effectiveness in 76.5% (n = 13/17). The four patients with ineffective t-PA therapy underwent subsequent surgical HVAD exchange. Multiple Cox regression model analysis revealed time interval between HVAD implantation and first thrombosis as an independent risk factor of recurrent thrombosis (HR, 0.93, 95% CI 0.87-0.99, p = 0.031). Kaplan-Meier analysis at 3 year follow-up showed no significant difference in overall survival for recurrent vs non-recurrent thrombosis groups (log-rank test, p = 0.959). CONCLUSION: Recurrent HVAD thrombosis mostly appears within 12 months after first thrombosis. Systemic t-PA therapy for recurrent pump thrombosis seems safe, achieving comparable effectiveness rates to initial t-PA therapy. Survival does not differ between patients with or without recurrent HVAD thrombosis.

Adsorption/desorption process of formaldehyde onto iron doped graphene: a theoretical exploration from density functional theory calculations.

The interaction of formaldehyde (H2CO) onto Fe-doped graphene (FeG) was studied in detail from density functional theory calculations and electronic structure analyses. Our aim was to obtain insights into the adsorption, desorption and sensing properties of FeG towards H2CO, a hazardous organic compound. The adsorption of H2CO was shown to be energetically stable onto FeG, with adsorption energies of up to 1.45 eV and favored in different conformations. This interaction was determined to be mostly electrostatic in nature, where the oxygen plays an important role in this contribution; besides, our quantum molecular dynamics results showed the high stability of the FeG-H2CO interaction at ambient temperature (300 K). All the interactions were determined to be accompanied by an increase in the HOMO-LUMO energy gap with respect to the isolated adsorbent, indicating that FeG is highly sensitive to H2CO with respect to pristine graphene. Finally, it was found that external electric fields of 0.04-0.05 a.u. were able to induce the pollutant desorption from the adsorbent, allowing the adsorbent reactivation for repetitive applications. These results indicate that FeG could be a promising candidate for adsorption/sensing platforms of H2CO.

Oxidized and Si-doped graphene: emerging adsorbents for removal of dioxane.

Graphene-based materials have emerged as new potential adsorbents for the adsorption and removal of persistent pollutants, and they could play a key role in the remediation of 1,4-dioxane. In this framework, a quantum chemistry study was carried out to rationalize the sorption properties of oxidized graphene (GO) and Si-doped graphene (SiG) nanosheets for use in 1,4-dioxane removal, taking into account that these adsorbents are experimentally available. Dispersion corrected PBE-D3/SVP calculations show that GO and SiG adsorbs dioxane through non-covalent and covalent interactions, respectively, with adsorption energies of up to ∼0.9 eV, which represents an important improvement with respect to the adsorption onto intrinsic graphene. The adsorption strength was also rationalized in terms of natural bond orbitals, atoms-in-molecules and energy decomposition analyses. In the case of GO, a high content of hydroxyl and carboxyl functional groups enhances the removal efficiency, and they are responsible for the high adsorption stability in aqueous environments and at room temperature (300 K). In addition, explicit/implicit solvent calculations and molecular dynamics trajectories show that the SiG-dioxane interaction is highly stable at 300 K, without pollutant diffusion; besides, the SiG-dioxane interaction is stabilized in the presence of H2O molecules. All the analyses suggest that GO and SiG should be considered as new remarkable candidates for sorption technologies related to the removal, control and remediation of 1,4-dioxane, where the sorption efficiency is sorted as SiG > GO ≫ G.

In Vitro Evaluation of Inflow Cannula Fixation Techniques in Left Ventricular Assist Device Surgery.

The therapy of terminal heart failure with left ventricular assist devices has become a standard in cardiac surgery. Yet the surgical implantation technique is not standardized and differs from center to center. Complications associated with left ventricular assist device (LVAD) inflow cannula placement are thrombosis, suction events, and flow disturbances. Within this in vitro study we aimed to investigate if the fixation technique of the sewing ring has an impact on the position of the inflow cannula. For this in vitro study the HeartMate III LVAD (Thoratec Corporation, Pleasanton, CA, USA) was used. In five sessions, two approaches were considered for coring of the ventricle for LVAD inflow cannula insertion: "sew-then-core" and "core-then-sew." In the "sew-then-core" technique, the sewing cuff is first affixed to the heart, usually with 8-16 interrupted pledgeted mattress sutures. Subsequently, a cylindrical knife is used to resect a cylindrical core of myocardium to permit cannula insertion. In the "core-then-sew" technique, the sequence is reversed such that the knife is used before the suture ring is affixed. When the "sew-then-core" technique is used, the mattress sutures may be placed with full-thickness bites that penetrate the endocardium (i.e., transmural stitching) or partial-thickness bites that do not penetrate the endocardium (i.e., epicardial stitching). When the "core-then-sew" technique is used, the suture is passed fully into the ventricular lumen and fed back through the cored hole, at which point the needle may be reinserted into the freshly cored myocardium such that it exits the epicardium (i.e., transmural stitching with back stitch) or not (i.e., transmural stitching without back stitch). These four different sewing ring fixation suturing techniques were tested by experienced surgeons to affix the sewing ring: transmural stitching, epicardial stitching, transmural stitching with back stitch, and transmural stitching without back stitch. The sewing ring was sewed onto a silicone dummy designed to simulate the left ventricle with standard 2-0 Ethibond sutures (Ethicon, Somerville, NY, USA). Afterward, the dummies were measured and documented via photography. In addition, porcine hearts were used to simulate the suturing techniques in a physiological setting. The setting of the inflow cannula is substantially influenced by the fixation method of the sewing ring. Epicardial stitching showed the best results with stable cannula fixation, minimal gap around the cannula and no contact between the sutures and sewing ring with blood. The method of transmural stitching without back stitch showed the worst results by creating the biggest epithelial gap between inflow cannula and tissue as well as proving the biggest surface for blood contact between sewing ring and sutures. In general, both "sew-then-core" techniques resulted in a greater degree of apposition between the cuff and epicardial tissue. Within the study we revealed that the surgical fixation of the sewing ring has a significant impact on the inflow cannula stability, position, and tissue apposition in LVAD implantation surgery. Epicardial stitching of the sewing ring provides the best results in order to prevent suction events as well as thrombosis formation.

Multimodal Imaging for In Vivo Evaluation of Induced Pluripotent Stem Cells in a Murine Model of Heart Failure.

Myocardial stem cell therapy in heart failure is strongly dependent on successful cellular transfer, engraftment, and survival. Moreover, massive cell loss directly after intramyocardial injection is commonly observed, generating the need for efficient longitudinal monitoring of transplanted cells in order to develop more efficient transplantation techniques. Therefore, the aim of the present study was to assess viability and cardiac retention of induced pluripotent stem cells after intramyocardial delivery using in vivo bioluminescence analysis (BLI) and magnetic resonance imaging (MRI). Murine induced pluripotent stem cells (iPSCs) were transfected for luciferase reporter gene expression and labeled intracellularly with supraparamagnetic iron oxide particles. Consequently, 5 × 105 cells were transplanted intramyocardially following left anterior descending coronary artery ligation in mice. Cardiac iPSCs were detected using BLI and serial T2* sequences by MRI in a 14-day follow-up. Additionally, infarct extension and left ventricular (LV) function were assessed by MRI. Controls received the same surgical procedure without cell injection. MRI sequences showed a strong MRI signal of labeled iPSCs correlating with myocardial late enhancement, demonstrating engraftment in the infarcted area. Mean iPSC volumes were 4.2 ± 0.4 mm3 at Day 0; 3.1 ± 0.4 mm3 at Day 7; and 5.1 ± 0.8 mm3 after 2 weeks. Thoracic BLI radiance decreased directly after injection from 1.0 × 106 ± 4.2 × 104 (p/s/cm2 /sr) to 1.0 × 105 ± 4.9 × 103 (p/s/cm2 /sr) on Day 1. Afterward, BLI radiance increased to 1.1 × 106 ± 4.2 × 104 (p/s/cm2 /sr) 2 weeks after injection. Cardiac graft localization was confirmed by ex vivo BLI analysis and histology. Left ventricular ejection fraction was higher in the iPSC group (30.9 ± 0.9%) compared to infarct controls (24.0 ± 2.1%; P < 0.05). The combination of MRI and BLI assesses stem cell fate in vivo, enabling cardiac graft localization with evaluation of LV function in myocardial infarction.

Chronic ventricular assist device support: surgical innovation.

PURPOSE OF REVIEW: Ventricular assist device (VAD) therapy is currently one of the fastest-developing fields in cardiac surgery. Consistently improved technology, research, and gain of clinical experience have established VADs as an important option for the treatment of congestive heart failure. During the past year, novel devices and less invasive surgical procedures have been revolutionizing this field. The purpose of this manuscript is to review these innovations with special emphasis on device-related surgery. RECENT FINDINGS: Device miniaturization has enabled less invasive VAD surgery, excluding the need for full sternotomy. Recent data show that intrahospital survival rates following less invasive VAD implantation are surpassing 90%. Secondly, two new devices, Heartmate 3 and MVAD, are being applied and tested for clinical application. In this context, the Heartmate 3 CE mark study recently concluded with excellent outcomes and without any pump thrombosis or device malfunctions. SUMMARY: The first clinical results of the newest generation of VADs are very promising compared with old-generation devices. Furthermore, less invasive surgery is becoming a standard for the implantation, exchange, or explantation of left VADs. The joint venture of improved technology and innovative surgical techniques will push this field forward to even better outcomes and reduced complication rates.