[The application of negative pressure wound therapy (NPWT) in potentially lethal conditions]. / A negatív nyomással végzett sebkezelés (NPWT) alkalmazása potenciálisan letális állapotokban.

Bemutatásra kerülo esetünkben egy 47 éves, generalizált septicus állapotú férfi beteg komplex terápiás megoldást igénylo kezelését ismertetjük, negatív nyomásterápia segítségével (NPWT). A páciens kezeletlen diabéteszes láb szindróma talaján kialakult szepszis, fasciitis necrotisans klinikai-radiomorfológiai képével került osztályunkra, akinél sürgosséggel feltárást, az alsó végtag valamennyi kompartmentjét érinto fasciotomiát végeztünk, NPWT-kezelést indítottunk. Kezelése során a beteg állapotát súlyosbító szövodmények léptek fel: Curling-fekély, toxicus epidermalis necrolysis (TEN). A fascitis kapcsán kialakult kb. 6% TBSA (total body surface area) kiterjedésu hámhiányt a TEN-szindróma további epidermális állományvesztéssel tovább súlyosbította. Állapotstabilizálást, kezdeti lokalis kontroll biztosítását követoen a hámhiányos felület csökkentése érdekében a sebeket szukítettük, a feltisztult sebalapok fedése 1:3 arányban hálósított félvastag bor transzplantációjával történt. Az NPWT-kezelést a transzplantációt követoen is folytattuk. A beteg három hónapos intenzív osztályos és sebészeti kezelést követoen sebészi szempontból meggyógyult. A negatív nyomásterápia korai - a kórlefolyásnak megfelelo - adekvát üzemmódban és fedési technikával történo alkalmazása a végtagvesztéssel és életveszéllyel járó nagy fokú hámhiány esetében hatékony eszköznek bizonyult. A multidiszciplináris terápiának köszönhetoen betegünk sebészeti alapbetegségét sikeresen gyógyítottuk, azonban az évtizedes tartamú kezeletlen cukorbetegsége, SARS-Covid peumoniája, a relabáló septicus állapota során fellépo szövodmények következtében felépülni már nem tudott.

The Inhibitor Preincubation Effect Is Universal to SLC Transporter Assays and Is Only Partially Eliminated in the Presence of Extracellular Protein.

Variation in the methodology of in vitro transporter inhibition assays causes wide divergence in reported IC50/Ki data. Notably, although potentiation of transporter inhibition by preincubation (PTIP) has been described, current guidelines do not specifically recommend inhibitor preincubation; they only encourage sponsors to follow emerging literature. To clarify how generally preincubation should be considered in transporter inhibition studies and whether PTIP can be solely explained by protein binding of the respective inhibitors, we performed in vitro inhibition assays on solute carrier (SLC) and ATP-binding cassette transporters scarcely or not covered in prior research and examined the effect of extracellular protein in preincubation and washout experiments. In SLC assays without extracellular protein, a 30-minute preincubation caused significant > twofold change of IC50 in 21/33 transporter-inhibitor combinations involving 19 evolutionarily disparate transporters. The preincubation effect correlated with inhibitor properties like protein binding and aqueous solubility. In vesicular transport assays of multidrug resistance protein 1, breast cancer resistance protein, multidrug resistance-associated protein 2, and bile salt export pump, sizable PTIP was observed for only 2/23 combinations, and preincubation was practically inconsequential in breast cancer resistance protein or multidrug resistance protein 1 monolayer assays. In SLC assays, PTIP partly persisted in the presence of 5% albumin, indicating that the absence of extracellular protein does not fully explain PTIP. The presence of protein, however, complicated the interpretation of results. Overall, while preincubating without protein may overpredict inhibitory potency, adding protein compromises clarity, and omitting preincubation altogether may miss clinically relevant inhibitors. Therefore, we propose that protein-free preincubation should be considered in all SLC inhibition assays. ATP-binding cassette transporter inhibition seems less commonly affected by preincubation, but conclusions require further investigation. SIGNIFICANCE STATEMENT: Drugs may inhibit transporter proteins in the body, which may precipitate drug interactions. In vitro transporter inhibition assays help predict such drug interactions. Some inhibitors act more potently when preincubated with the transporter prior to the assay. Here we argue that this effect is not a mere in vitro artifact due to the lack of plasma proteins and should be considered in all uptake inhibition assays to model the worst-case scenario. Preincubation in efflux transporter inhibition assays is likely dispensable.

Minimal Impacts of Microplastics on Soil Physical Properties under Environmentally Relevant Concentrations.

Agricultural soils are a major reservoir of microplastics, and concerns have arisen about the impacts of microplastics on soil properties and functioning. Here, we measured the physical properties of a silt loam in response to the incorporation of polyester fibers and polypropylene granules over a wide range of concentrations. We further elucidated the underlying mechanisms by determining the role of microplastic shape and the baseline effects from the amendment of soil particles. The incorporation of microplastics into soil tended to increase contact angle and saturated hydraulic conductivity and decrease bulk density and water holding capacity, but not affect aggregate stability. Polyester fibers affected soil physical properties more profoundly than polypropylene granules, due to the vastly different shape of fibers from that of soil particles. However, changes in soil properties were gradual, and significant changes did not occur until a high concentration of microplastics was reached (i.e., 0.5% w/w for polyester fibers and 2% w/w for polypropylene granules). Currently, microplastic concentrations in soils not heavily polluted with plastics are far below these concentrations, and results from this study suggest that microplastics at environmentally relevant concentrations have no significant effects on soil physical properties.

A Multi-Omics Approach Reveals Features That Permit Robust and Widespread Regulation of IFN-Inducible Antiviral Effectors.

The antiviral state, an initial line of defense against viral infection, is established by a set of IFN-stimulated genes (ISGs) encoding antiviral effector proteins. The effector ISGs are transcriptionally regulated by type I IFNs mainly via activation of IFN-stimulated gene factor 3 (ISGF3). In this study, the regulatory elements of effector ISGs were characterized to determine the (epi)genetic features that enable their robust induction by type I IFNs in multiple cell types. We determined the location of regulatory elements, the DNA motifs, the occupancy of ISGF3 subunits (IRF9, STAT1, and STAT2) and other transcription factors, and the chromatin accessibility of 37 effector ISGs in murine dendritic cells. The IFN-stimulated response element (ISRE) and its tripartite version occurred most frequently in the regulatory elements of effector ISGs than in any other tested ISG subsets. Chromatin accessibility at their promoter regions was similar to most other ISGs but higher than at the promoters of inflammation-related cytokines, which were used as a reference gene set. Most effector ISGs (81.1%) had at least one ISGF3 binding region proximal to the transcription start site (TSS), and only a subset of effector ISGs (24.3%) was associated with three or more ISGF3 binding regions. The IRF9 signals were typically higher, and ISRE motifs were "stronger" (more similar to the canonical sequence) in TSS-proximal versus TSS-distal regulatory regions. Moreover, most TSS-proximal regulatory regions were accessible before stimulation in multiple cell types. Our results indicate that "strong" ISRE motifs and universally accessible promoter regions that permit robust, widespread induction are characteristic features of effector ISGs.

First DNA sequence proof for the occurrence of bovine adenovirus types 10 and 11 in continental Europe.

Bovine adenoviruses (BAdV) are known to cause respiratory and/or intestinal disease in calves. Infection can manifest as acute outbreaks, but more often only sporadic cases occur. Here we describe the PCR detection and partial sequence characterization of several BAdVs found in sick or dead calves on different farms in Western Hungary. Intermittent diarrhoeal illnesses occurred after weaning among calves on several farms located up to 40 km apart. A high-sensitivity, broad-spectrum nested PCR, developed for the general detection of adenoviruses, gave positive results in four independent cases. Direct sequencing of PCR products showed clear results from only two samples, whereas sequences from the other two amplicons were mixed. Molecular cloning of these heterogeneous PCR products was performed to separate each DNA fragment therein. By sequencing several plasmid clones from both mixed samples, we were able to detect the simultaneous presence of two different BAdV types, namely types 6 and 10 classified into two separate (Atadenovirus and Mastadenovirus) genera. The sequence of one homogenous sample was identified as being derived also from BAdV-10, whereas the other sample contained a novel type, proposed to be BAdV-11. We demonstrated, for the very first time, the occurrence of the two latter virus types in continental Europe. Their appearance in Hungary marks a significant shift in the types of BAdVs actually circulating in the country. Considering the similarity of the pathological findings to those, attributed to BAdV-10 infections reported to date, the causative role of the viruses in these cases seems to be plausible. Phylogeny reconstruction further confirmed that BAdVs represent multiple genetic lineages.

Ripples at edges of blooming lilies and torn plastic sheets.

Ripples arise at edges of petals of blooming Lilium casablanca flowers and at edges of torn plastic sheets. In both systems, ripples are a consequence of excess length along the edge of a sheet. Through the use of time-lapse videos of blooming lilies and published images of torn plastic sheets, we find that ripples in both systems are well described by the scaling relationship a∝w(L-w), where a is amplitude, w is wavelength, and L is arc length. A phenomenological relationship previously reported for self-similar ripple patterns, namely ⟨a⟩∝⟨w⟩, can be recovered by assuming that buckling stress is constant. Excess length along petal edges can also influence their overall Gaussian curvature, such that petals invert from a cup shape to a saddle shape upon blooming. Previous simulations of these shape changes have assumed that petal thickness decreases at least quadratically. Here, we evaluate tomograms of several varieties of lily buds and find that this assumption is valid along the short axis of the buds, but not the long axis. A challenge of employing traditional tomography methods to measure petal thickness is that the sample is destroyed; a single bud cannot be followed through the entire blooming process. To address this challenge, we provide proof of principle that the nondestructive, label-free method of x-ray tomography produces high-contrast three-dimensional scans on time scales short enough to follow lily blooming.

The potential of radiocarbon analysis for the detection of art forgeries.

Art objects form an essential part of cultural heritage and are appreciated for their artistic values. However, the observed investment in art and capacity for high monetary returns encourages counterfeiting of art objects. The art market's lack of transparency and traditional confidential protocols amplifies the problem. Radiocarbon analysis provides a tool to detect anachronistic materials. Measurement of bomb peak radiocarbon, which was observed in the atmosphere during the last 70 years, can provide clear evidence of post-1950 material. Here we briefly introduce the method and discuss its application in detecting forgeries. Three accelerator mass spectrometry AMS laboratories performed a 14C dating inter-comparison study on the material used in art. Results obtained on modern cotton paper, two antique sheets of paper, one parchment, and one textile demonstrate the radiocarbon dating capacity to date the material accurately. The excellent agreement between laboratories is crucial for the broader application of this scientific tool in forensic studies and court cases.

Tuning the Charge and Hydrophobicity of Graphene Oxide Membranes by Functionalization with Ionic Liquids at Epoxide Sites.

Functionalization of graphene oxide (GO) membranes is generally achieved using carboxyl groups as binding sites for ligands. Herein, by taking advantage of the ability of imidazolium-based ionic liquids (ILs) to undergo an epoxide ring-opening reaction, a new approach of GO modification was established, in which ILs were bonded to the abundant epoxides on GO without sacrificing the carboxyl groups. Computational methods confirmed this unique configuration of ILs on GO, which enabled the dispersion of IL/GO flakes in water for facile casting into laminate membranes. Compared with neat GO, the ILs in IL/GO membranes served as spacers that substantially reduced the multi-valent cation mobility, simultaneously facilitated ion desolvation, and increased the water flux across the membrane. Our studies found that the higher separation efficiency of IL/GO membranes may be attributed to the synergistic modification of the hydrophobicity and surface charge. Specifically, the protonated nitrogen of the imidazolium cations altered the surface charge of GO, thereby generating electrostatic repulsion that enhanced the selectivity of cation rejection. On the other hand, the increased length of the alkyl chains bound to the imidazolium rings was found to increase the hydrophobicity of GO, which, in turn, aided the fine-tuning of the water desolvation/transport dynamics at the GO/IL interface to achieve a high water flux. Additionally, the water retention was reduced on the hydrophobic planes, which inhibited GO swelling during aqueous separations. Molecular dynamics simulations revealed increased water diffusivity when ILs were intercalated within GO layers. We establish that without requiring a high energy input, functionalization of GO membranes with ILs may be a promising approach to achieve efficient ion separation and critical material recovery.

The behavior of iodine in stabilized granular activated carbon and silver mordenite in cementitious waste forms.

Both granular activated carbon (GAC) and silver mordenite (AgM) are utilized for the removal of contaminants and radionuclides (e.g., radioiodine) from off-gas streams in nuclear fuel reprocessing and high temperature immobilization of nuclear waste. Following their service lifetimes, the GAC and AgM contain an inventory of contaminants and radionuclides and require stabilization in a matrix for disposal. GAC and AgM are referred to as solid secondary waste (SSW) materials. Cementitious waste forms can be used as the stabilization matrix for SSW, however, for successful stabilization, the inclusion of GAC and AgM should not negatively impact the physical behavior of the cementitious waste form or increase release of the contaminants/radionuclides compared to the baseline case without stabilization. The present work focuses on evaluation of cement formulations, with and without slag, for the stabilization of iodine-loaded GAC or AgM. The results showed that both a slag-containing and slag-free formulations were able to stabilize GAC and AgM, up to 30 vol%, without deleterious impacts on the bulk physical properties of the encapsulating matrix. When monolithic samples of the GAC or AgM containing cement formulations were subjected to leach tests, it was observed that iodide leached from the SSW) had limited sorption to either of the cement matrices. Nonetheless, the iodine can interact with the SSW materials themselves. Specifically, iodine retention within monolithic samples containing the iodine-loaded GAC or AgM was improved for AgM containing waste forms while no improvement was observed for the GAC containing waste forms. The improvement for the AgM containing waste forms was likely due to an enrichment of Ag at the interface between the AgM particles and the cement matrix that can impede iodine migration out from the waste form. The results are significant in highlighting the potential for long-term retention of iodine in specific cementitious waste forms.

Perioperative Factor Concentrate Use is Associated With More Beneficial Outcomes and Reduced Complication Rates Compared With a Pure Blood Product-Based Strategy in Patients Undergoing Elective Cardiac Surgery: A Propensity Score-Matched Cohort Study.

OBJECTIVE: The goal of this study was to compare factor concentrate (FC)-based and blood product-based hemostasis management of coagulopathy in cardiac surgical patients in terms of postoperative bleeding, required blood products, and outcome. DESIGN: Retrospective, propensity score-matched analysis. SETTING: Single, tertiary, academic medical center. PARTICIPANTS: One hundred eighteen matched pairs of 433 consecutive patients scheduled for cardiac surgery in two isolated periods with distinct strategies of hemostasis management. INTERVENTIONS: Patients received either blood product-based (period I) or FC-based (period II) hemostasis management to treat perioperative coagulopathy. MEASUREMENTS AND MAIN RESULTS: Patients treated with FC management experienced less postoperative blood loss (907 v 1,153 mL, p = 0.014) and required less red blood cell and fresh frozen plasma transfusion (2.3 v 3.7 units p < 0.0001, and 2.0 v 3.4 units p < 0.0001, respectively) compared with subjects in the blood product-based management group. The frequency of Stage 3 acute kidney injury and 30-day mortality rate were significantly higher in the blood product-based group than in the FC management group (6.8% v 0.8%, p = 0.016, and 7.2% v 0.8%, p = 0.022, respectively). FC management-related thromboembolic events were not registered. The FC strategy was associated with a 2.19-fold decrease in the odds of massive postoperative bleeding (p < 0.0001), a 2.56-fold decrease in the odds of polytransfusion (p < 0.0001), and a 13.16-fold decrease in the odds of early postoperative death (p = 0.003). CONCLUSIONS: FC-based versus blood product-based management is associated with reduced blood product needs and fewer complications, and was not linked to a higher frequency of thromboembolic events or a decrease in long-term survival in cardiac surgical patients developing perioperative coagulopathy and bleeding.

A growth factor-expressing macrophage subpopulation orchestrates regenerative inflammation via GDF-15.

Muscle regeneration is the result of the concerted action of multiple cell types driven by the temporarily controlled phenotype switches of infiltrating monocyte-derived macrophages. Pro-inflammatory macrophages transition into a phenotype that drives tissue repair through the production of effectors such as growth factors. This orchestrated sequence of regenerative inflammatory events, which we termed regeneration-promoting program (RPP), is essential for proper repair. However, it is not well understood how specialized repair-macrophage identity develops in the RPP at the transcriptional level and how induced macrophage-derived factors coordinate tissue repair. Gene expression kinetics-based clustering of blood circulating Ly6Chigh, infiltrating inflammatory Ly6Chigh, and reparative Ly6Clow macrophages, isolated from injured muscle, identified the TGF-ß superfamily member, GDF-15, as a component of the RPP. Myeloid GDF-15 is required for proper muscle regeneration following acute sterile injury, as revealed by gain- and loss-of-function studies. Mechanistically, GDF-15 acts both on proliferating myoblasts and on muscle-infiltrating myeloid cells. Epigenomic analyses of upstream regulators of Gdf15 expression identified that it is under the control of nuclear receptors RXR/PPARγ. Finally, immune single-cell RNA-seq profiling revealed that Gdf15 is coexpressed with other known muscle regeneration-associated growth factors, and their expression is limited to a unique subpopulation of repair-type macrophages (growth factor-expressing macrophages [GFEMs]).

Rape, sunflower and forest honeys for long-term environmental monitoring: Presence of indicator elements and non-photosynthetic carbon in old Hungarian samples.

In this paper, we present the time-dependent elemental composition and AMS radiocarbon dating results of 36 rape, sunflower and forest honey samples, collected between 1985 and 2018 in geographically close locations. Based on the elemental information, we conclude that bee products regardless the type provide useful environmental information of the previous decades, such as the decreasing trend of airborne Pb emission can be traced. However, radiocarbon results agree less with the atmospheric bomb peak. Random offsets were observed in the specific radiocarbon activity of the honey samples indicating that rape, sunflower and forest honey samples are not as reliable materials for radiocarbon dating as acacia honeys. The radiocarbon results show that the rape, sunflower and forest honey samples can contain non-photosynthetic carbon, presumably derived from the soil. Thus, the complex application of honey samples for environmental reconstruction requires the species-separated investigation of bee products to reveal their adaptability for assessment approaches.

Understanding the Electronic Structure Evolution of Epitaxial LaNi1-xFexO3 Thin Films for Water Oxidation.

Rare earth nickelates including LaNiO3 are promising catalysts for water electrolysis to produce oxygen gas. Recent studies report that Fe substitution for Ni can significantly enhance the oxygen evolution reaction (OER) activity of LaNiO3. However, the role of Fe in increasing the activity remains ambiguous, with potential origins that are both structural and electronic in nature. On the basis of a series of epitaxial LaNi1-xFexO3 thin films synthesized by molecular beam epitaxy, we report that Fe substitution tunes the Ni oxidation state in LaNi1-xFexO3 and a volcano-like OER trend is observed, with x = 0.375 being the most active. Spectroscopy and ab initio modeling reveal that high-valent Fe3+δ cationic species strongly increase the transition-metal (TM) 3d bandwidth via Ni-O-Fe bridges and enhance TM 3d-O 2p hybridization, boosting the OER activity. These studies deepen our understanding of structural and electronic contributions that give rise to enhanced OER activity in perovskite oxides.

Pseudoaneurysm of the ascending aorta: case report of a donor-derived Pseudomonas infection in a heart transplant recipient.

BACKGROUND: Mycotic aortic pseudoaneurysm is a rare complication after heart transplantation (HTX) with remarkable mortality. Intrathoracic infection is a well-documented predisposing factor for this disease. Staphylococcus aureus, Pseudomonas aeruginosa or Candida species are commonly isolated from resected specimens of the pseudoaneurysms. We demonstrate a unique case of mycotic pseudoaneurysm caused by presumably donor-derived Pseudomonas infection in a heart transplant recipient. CASE PRESENTATION: Our 67-year-old male patient treated with diabetes mellitus underwent HTX. The donor suffered from epiglottic abscess and pneumonia with known microorganisms including Pseudomonas, therefore both the donor and recipient received targeted antimicrobial therapy and prophylaxis. Five months after the uneventful HTX, lab test of the asymptomatic patient showed moderate, increasing C-reactive protein level without obviuos source of infection. Chest computed tomography showed a large (90 mm) saccular dilatation of the tubular portion of ascending aorta. Urgent surgical intervention identified a pseudoaneurysm, histological examinations and cultures of the resected aorta verified Pseudomonas aeruginosa aortitis, while all blood cultures remained negative. Retrospective interrogation of other transplanted organs of the donor supported donor-derived infection as the transport fluid of the right kidney grew Pseudomonas. The patient received 3 weeks of ceftazidime followed by 7 months of oral ciprofloxacin therapy. One year after the operation the patient was asymptomatic with normal inflammatory markers. CONCLUSIONS: Donor-derived infection is a rare but potential cause of aortitis. Early diagnosis, surgical intervention and adjuvant antibiotic therapy seem to be the keys to successful management of mycotic pseudoaneurysms after HTX.

Radiocarbon in the atmospheric gases and PM10 aerosol around the Paks Nuclear Power Plant, Hungary.

Our study shows a one-year-long, monthly integrated continuous monitoring campaign of gaseous radiocarbon emission and ambient air compared with 4 event-like, weekly (168 h) atmospheric aerosol radiocarbon data in every season of 2019, at 4 locations (n = 16 aerosol sample) around the Paks Nuclear Power Plant, Hungary. The study shows the first aerosol radiocarbon results around a nuclear power plant measured by accelerator mass spectrometry in Hungary. There was no dominant contribution detected in the atmospheric CO2 gas fraction, but we could detect excess radiocarbon in the total gaseous carbon fraction at almost every sampling point around the Paks Nuclear Power Plant. The highest Δ14C value in the total gaseous carbon form was 157.9 ± 4.6‰ in November and the highest Δ 14C value in the CO2 fraction was 86.1 ± 4.0‰ in December during 2019. Observed 14C activity excess is not higher than previously published values around the Paks Nuclear Power plant at the same sampling points (Molnár et al., 2007; Varga et al., 2020). Our aerosol radiocarbon measurements show that there is no significant contribution from the nuclear power plant to the atmospheric PM10 fraction. We could not detect a Δ 14C value higher than 0‰ in any season. The results show that the simple aerosol sampling, without pre-treatment of the filters, is appropriate for the measurement of excess radiocarbon at the vicinity of nuclear power plants. The applied preparation and measurement method can be applicable for detection of hot (14C) particles and early identification of radiocarbon emission from nuclear power plants in the PM10 fraction.

Acute heart transplantation from mechanical circulatory support in a human immunodeficiency virus-positive patient with fulminant myocarditis.

Since the establishment of highly active antiretroviral therapy, survival rates have improved among patients with human immunodeficiency virus infection giving them the possibility to become transplant candidates. Recent publications revealed that human immunodeficiency virus-positive heart transplant recipients' survival is similar to non-infected patients. We present the case of a 40-year-old human immunodeficiency virus infected patient, who was hospitalized due to severely decreased left ventricular function with a possible aetiology of acute myocarditis, that has later been confirmed by histological investigation of myocardial biopsy. Due to rapid progression to refractory cardiogenic shock, extracorporeal membrane oxygenation implantation had been initiated, which was upgraded to biventricular assist device later. On the 35th day of upgraded support, the patient underwent heart transplantation uneventfully. Our clinical experience confirms that implementation of temporary mechanical circulatory support and subsequent cardiac transplantation might be successful in human immunodeficiency virus-positive patients even in case of new onset, irreversible acute heart failure.

Competitive TcO4-, IO3-, and CrO42- Incorporation into Ettringite.

Ettringite is a naturally occurring mineral found in cementitious matrices that is known for its ability to incorporate environmentally mobile oxyanion contaminants. To better assess this immobilization mechanism for contaminants within cementitious waste forms intended for nuclear waste storage, this work explores how mixed oxyanion contaminants compete for ettringite incorporation and influence the evolving mineralogy. Ettringite was precipitated in the presence of TcO4-, IO3-, and/or CrO42-, known contaminants of concern to nuclear waste treatment, over pre-determined precipitation periods. Solution analyses quantified contaminant removal, and the collected solid was characterized using bulk and microprobe X-ray diffraction coupled with pair distribution function and microprobe X-ray fluorescence analyses. Results suggest that ≥96% IO3- is removed from solution, regardless of ettringite precipitation time or the presence of TcO4- or CrO42-. However, TcO4- removal remained <20%, was not significantly improved with longer ettringite precipitation times, and decreased to zero in the presence of IO3-. When IO3- is co-mingled with CrO42-, calcite and gypsum are formed as secondary mineral phases, which allows for oxyanion partitioning, e.g., IO3- incorporation into ettringite, and CrO42- incorporation into calcite. Results from this work exemplify the importance of competitive immobilization when assessing waste form performance and environmental risk of contaminant release.