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A világjárvány következtében jelentősen emelkedett a telemedicinális ellátási formákkal kapcsolatos publikációk száma, jól érzékelhetően fokozódtak a kormányzati törekvések a szabályozás minőségi javítására, az egészségügyi szereplők pedig a korábbiakhoz képest nagyobb intenzitással és szélesebb spektrumban kezdték el alkalmazni a rendelkezésre álló technikai lehetőségeket. A bevezetett korlátozások következtében nemcsak az orvosok, hanem a lakosság részéről is megnövekedett igény tapasztalható az online térben zajló konzultációk, tanácsadások és orvosi vizitek lebonyolítására. Cikkünkben azt elemezzük, hogy a jelenleg ismert digitális platformokat és telemedicinális rendszereket mely területen használták fel, mely faktorok indukálták fejlődésüket, illetve hogyan képesek ezek kiszolgálni a katonai betegellátás igényeit a több mint egy éve zajló koronavírus-világjárvány idején. Ugyancsak kísérletet teszünk arra, hogy megtaláljuk a telemedicina, az eHealth és mHealth rendszerek illesztési pontjait a Magyar Honvédség Honvédelmi és Haderőfejlesztési Programjának egyik fő elemét alkotó Digitális Katona Programjával.

Polyurethanes (PUs) are widely used in different applications, and thus various synthetic procedures including one or more catalysts are applied to prepare them. For PU foams, the most important catalysts are nitrogen-containing compounds. Therefore, in this work, the catalytic effect of eight different nitrogen-containing catalysts on urethane formation will be examined. The reactions of phenyl isocyanate (PhNCO) and methanol without and in the presence of catalysts have been studied and discussed using the G3MP2BHandHLYP composite method. The solvent effects have also been considered by applying the SMD implicit solvent model. A general urethane formation mechanism has been proposed without and in the presence of the studied catalysts. The proton affinities (PA) were also examined. The barrier height of the reaction significantly decreased (∆E0 > 100 kJ/mol) in the presence of the studied catalysts, which proves the important effect they have on urethane formation. The achieved results can be applied in catalyst design and development in the near future.

One of the most important possible complications determining long-term graft survival after kidney transplant is antibody-mediated rejection (ABMR). The criterion standard approach to recognize ABMR is currently the kidney biopsy with histopathologic analysis. However, this test has limitations because of difficulties in timing of sampling, the evaluability of histology because of the questionable representativeness of specimens, and the limited number of this intervention. Hence, new reliable, noninvasive biomarkers are required to detect the development of ABMR in time.In this study, we analyzed the clinical data of 45 kidney transplant patients (mean age of 44.51 years, 20 male and 25 female subjects). These participants were recruited into 5 subcohorts based on their clinical status, histologic findings, and level of donor-specific anti-HLA antibodies. Circulating microRNAs (miR-21, miR-181b, miR-146a, miR-223, miR-155, miR-150) in plasma samples were quantified by quantitative polymerase chain reaction and their levels were correlated with the clinical characteristics in different subgroups.The relative expression of plasma miR-155 (P = .0003), miR-223 (P = .0316), and miR-21 (P = .0147) were significantly higher in patients who had subsequent histology-approved ABMR with donor-specific anti-HLA antibody positivity (n = 10) than in the "triple negative" group (n = 21), and miR-155 showed the highest sensitivity (90%) and specificity (81%) to indicate ABMR development based on receiver operating characteristic analysis.According to our preliminary data, plasma miR-155, miR-21, and miR-223 can indicate the development of ABMR after kidney transplant in correlation with classic clinical parameters. However, future studies with larger number of participants are necessary to further evaluate the diagnostic properties of blood miRNAs in prediction of this life-threatening condition.

A kinetic and mechanistic investigation of the alcoholysis of phenyl isocyanate (PhNCO) using stoichiometric butan-1-ol (BuOH) in acetonitrile in the presence of different tertiary amine catalysts was performed. The reaction mechanisms in the absence and presence of experimentally applied catalysts were described by using the G3MP2BHandHLYP composite method. The apparent activation energies obtained from the calculations were in good agreement with the experimental data (ΔΔ

A szerzők celja, hogy ravilagitsanak egy jelenleg meg hatarteruleti megjelenessel jellemezhető, de a koronavirus-vilagjarvany soran kiemelt szerepet elnyerő es egyre inkabb onallo domen formajaban megjelenő rendszer, a telemedicina jelentős ternyeresere. A betegseg termeszeteből adodo korlatozasok es az ezzel egyidőben a lakossag reszeről fokozodo egeszsegugyi ellatasi igeny egyuttesen emelte a telemedicinat az egeszsegugyi ellatas fokuszaba. Ennek kovetkezmenyekent jelent meg hazankban a jogalkotok reszeről azon torvenyi modositas, amely a telemedicina műkodeset mind szabalyozas, mind finanszirozasi oldalrol egyarant tamogatta. A szerzők a tanulmanyban arra keresik a valaszt, hogy a konvencionalis egeszsegugy mellett a telemedicinalis rendszer felfoghato-e mint onallo entitas, es ennek jogan a kozeljovőben alkalmassa valik-e majd arra, hogy a torvenyi szabalyozas szerint a letfontossagu rendszeri besorolassal jaro fokozott vedelmi prioritast elvezzen.Alternate abstract:At the moment, telemedicine can be characterised as a field which lays on the border of multiple specialties, however, in the course of the coronavirus pandemic, it gained a special role and it appears increasingly as a stand-alone domain, therefore, the aim of the authors is to shed a light on its remarkable headway. The restrictions that arise from the nature of the disease as well as the simultaneously rising need of the po pulation for healthcare collectively turned the focus of the healthcare system to telemedicine. As a result, the national lawmaker assisted the functioning of telemedicine with a legislative amendment on a regulatory as well as on a financing level. In this study the authors seek to address the question whether, besides the conventional health, telemedicine can be seen as a stand-alone entity. If so, based on this, it will be suitable to be classified as a critical infrastructrure in the near future, which would mean that telemedicine could enjoy the protection of an increased defence priority.

A havannai USA nagykövetségen dolgozók között 2016-ban újszerű, furcsa panaszok jelentkeztek. A dolgozók egy része erős fejfájásra, hányingerre, vibráló érzésre panaszkodott, amelyet egy igen erős hangingert követően észleltek. A tünetek enyhültek ugyan helyzetváltoztatásra, másik szobába történő áthaladásra, de az akut tünetek után krónikus panaszok jelentkeztek. A sokszor állandósuló fejfájás mellé memóriazavar, hallás- és látásproblémák, kognitív és pszichés zavarok társultak. Részletes kivizsgálásuk repatriálásukat követően az USA egyetemi kórházaiban zajlottak, ahol neurológiai, neuropszichológiai elváltozások voltak rögzíthetők, amelyet képalkotó vizsgálatok is megerősítettek. A tünetegyüttest Havanna szindrómának nevezték el, azóta azonban Kínában, az USA felségterületén, és legutóbb Ausztriában is előfordultak ilyen panaszok a diplomaták és a hírszerző közösség tagjai között. A tünetek hátterének felderítésére széleskörű egészségügyi, igazságügyi és hírszerző vizsgálat indult. Az Amerikai Egyesült Államok Külügyminisztériuma megbízásából az esetekről összefoglaló jelentést készített az Amerikai Mérnöki, Tudományos és Orvosi Akadémia tagjaiból álló munkacsoport. Megállapításuk alapján a tüneteket legvalószínűbben egy fókuszált, alacsony energiájú, pulzatilis rádiófrekvenciás besugárzás, szándékolt támadás okozhatta. A sugárzás okozta egészségügyi következményeket, a lehetséges egészségügyi és átfogó jellegű beavatkozásokat ismertetem a cikkben.

The alcoholysis of phenyl isocyanate (PhNCO) using stoichiometric butan-1-ol (BuOH) in acetonitrile in the presence of different cyclic amine catalysts was examined using a combined kinetic and mechanistic approach. The molecular mechanism of urethane formation without and in the presence of cyclic amine catalysts was studied using the G3MP2BHandHLYP composite method in combination with the SMD implicit solvent model. It was found that the energetics of the model reaction significantly decreased in the presence of catalysts. The computed and measured thermodynamic properties were in good agreement with each other. The results prove that amine catalysts are important in urethane synthesis. Based on the previous and current results, the design of new catalysts will be possible in the near future.

Percutaneous coronary intervention (PCI) is commonly used treatment for chronic total occlusion (CTO). PCI can be performed in two different ways using wire escalation (WE) or subintimal dissection and reentry (DR) technique. During both procedures patients are treated with anticoagulants, however a substantial activation of coagulation cascade is expected, which may affect clinical outcome.Our aim was to compare the impact of WE and DR techniques regarding endothelial cell activation and thrombin formation.Fifty patients after CTO-PCI were enrolled into this study. Blood samples were obtained before PCI, at 48 h and 3-6 months after the intervention to measure soluble endothelium-specific markers and to investigate thrombin generation.Twenty-nine patients were treated with WE, 21 received DR. In the DR group, soluble VCAM-1 (vascular cell adhesion molecule-1) and ICAM-1 (intercellular cell adhesion molecule-1) concentrations were gradually elevated and remained significantly increased at 3-6 months (p = 0.006 and p = 0.037, respectively) compared to pre-PCI. Furthermore, significant decrease in lagtime (p = 0.004) and time to peak (p = 0.002) with a substantial increment in peak thrombin (p = 0.001) were observed in these patients. In contrast, no significant alteration was found in the WE cohort. Clinical complications (myocardial infarction, stroke, thrombosis, revascularization) did not occur in the first 9 months of follow-up period in either group.Although DR intervention induces more thrombin generation with a larger degree of endothelium activation compared to WE, this technique does not cause more clinical complications.

B cells express various ion channels, but the presence of voltage-gated sodium (NaV) channels has not been confirmed in the plasma membrane yet. In this study, we have identified several NaV channels, which are expressed in the human B cell membrane, by electrophysiological and molecular biology methods. The sensitivity of the detected sodium current to tetrodotoxin was between the values published for TTX-sensitive and TTX-insensitive channels, which suggests the co-existence of multiple NaV1 subtypes in the B cell membrane. This was confirmed by RT-qPCR results, which showed high expression of TTX-sensitive channels along with the lower expression of TTX-insensitive NaV1 channels. The biophysical characteristics of the currents also supported the expression of multiple NaV channels. In addition, we investigated the potential functional role of NaV channels by membrane potential measurements. Removal of Na+ from the extracellular solution caused a reversible hyperpolarization, supporting the role of NaV channels in shaping and maintaining the resting membrane potential. As this study was mainly limited to electrophysiological properties, we cannot exclude the possible non-canonical functions of these channels. This work concludes that the presence of voltage-gated sodium channels in the plasma membrane of human B cells should be recognized and accounted for in the future.

Catalytic activity of different noble metal containing, N-BCNT-zeolite supported catalysts have been tested for benzophenone hydrogenation. It has been found that the palladium containing support-o...

Jelen tanulmányunkban – egy cikksorozat első részeként – Mária Terézia kevésbé ismert 1750- ben kiadott, hadirokkant ellátásról szóló rendeletét mutatjuk be. A pátensben az uralkodó az osztrák örökösödési háborúkban (1740-1748) részt vett nemzetek és a súlyos harcok során „a tagjaikat, egészségüket és épségüket feláldozó katonák” iránt érzett háláját kívánta kifejezni. A rendelet áttekintését követően kitérünk a rokkantkérdés megoldásának egy korabeli „sikeres” intézményére, a hadirokkantak telepítésére is. Cikksorozatunk második részében a Pesti Invalidus Ház történetét tekintjük át 1750-től az 1783-ban történt megszűnésig, különös tekintettel a rokkantrendelet 1772-ben történt revíziójára. Továbbá betekintést nyújtunk a rokkant katonák rendhagyó életpályájába, az „újrahasznosított” hadirokkantak kalandos hétköznapjaiba

A COVID-19 világjárvány következtében kialakult globális egészségügyi vészhelyzet a Föld összes kontinensét és teljes lakosságát érintette és érinti napjainkban is. A világjárvány komplex kihívásai folyamatosan próbára teszik az érintett országok egészségügyi ellátórendszereit. A járvány elleni védekezés során dinamikusan változó és fokozódó kihívások rámutatnak arra, hogy hasonló események bekövetkezésével a jövőben is nagy valószínűséggel számolnunk kell, azonban ezekre nem vagyunk megfelelő stratégiákkal felkészülve. Szembesülve a jelen helyzet kihívásaival, elemezve azok katasztrófaorvosi ellátásra vonatkozó részleteit, a Magyar Katonai Katasztrófaorvosi Társaság kidolgozta egy, az ellátás javítását szolgáló új képesség összetevőinek stratégiai besorolását, javasolt szerkezeti összetételét, várható feladatainak körét és várható beszerzési költségeit. A kidolgozásra került ellátó egységnek a „Katasztrófa Helyreállító Egység” nevet adta, amelynek angol elnevezése – Disaster Relief Unit.

Cikkunk aktualitasat a jelenleg is zajlo Covid-19 pandemia adja, amelynek soran előterbe kerultek mindazon telemedicinalis elemek, amelyek a korlatozott szemelyes orvos-beteg interakciokat potolva a virtualis terbe helyeződnek at. Jelen irasban a hazankkal szomszedos Ausztriara jellemző, a telemedicinaval kapcsolatosan jelenleg alkalmazott jogi szabalyozok legfontosabb teruleteit tekintjuk at, de kiterunk az adatvedelem szempontjabol relevans europai unios előirasokra is. Ennek a folyamatnak a jelenleg ervenyes, aktualisan jellemző kiindulasi statuszarol allitottuk ossze elemzesunket. A globalis gazdasagot, egeszsegugyet es tarsadalmi folyamatokat egyarant erintő Covid-19 pandemia varhatoan felgyorsitja a telemedicinat erintő jogalkotasi folyamatot es a sulyponti kerdesekre vonatkozo korrekcios lepesek vegrehajtasat. A kulfoldi helyzet megismerese, a pozitiv tapasztalatok atemelese elősegitheti a hazankban is egyre szelesebb korben hasznalt telemedicinahoz kapcsolodo jogi hatter biztonsaganak megteremteset.Alternate abstract:The actuality of our article is given by the ongoing Covid-19 pandemic. Due to this situation, the conventional doctor-patient physical interactions are strongly limited and a significant part of it moved to the virtual space. In this article we overview the most important sections of the current laws for telemedicine in the neighbouring Austria. Furthermore, we discuss the relevant data protection regulations of the European Union. Our analysis have been based of the current baseline status of this process. The acceleration of legislative process on telemedicine expected as a result of the Covid-19 pandemic affects global economy, health and social systems. Learning about the foreign situation and adopting the positive observations can support the development of the legal background of the more and more popular telemedicine in Hungary.

Although the majority of patients with Hodgkin lymphoma (HL) has recently become long-term survivors, 20%-30% of HL patients have primary refractory disease or relapse. It is essential to identify patients at risk of treatment failure during first-line therapy. To objective of the present study was to investigate the combined prognostic role of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (Between 01/01/2013 and 01/03/2019 77 HL patients were enrolled in this study where serum TARC levels were measured by an immunoassay andTwenty-six patients (34%) had early-stage HL, while 51 patients presented with advanced-stage disease. Fifteen patients had primary refractory HL, while 1 patient relapsed after first-line therapy. Optimal TARC cut-off value for progression-free survival (PFS) was 700pg/mL based on receiver operating characteristic (ROC) curve analysis. With Cox regression analysis,Interim

Objectives: Angiotensin-converting enzyme 2 (ACE2) represents the primary receptor for SARS-CoV-2 to enter endothelial cells. Here we investigated circulating ACE2 activity to predict the severity and mortality of COVID-19. Methods: Serum ACE2 activity was measured in COVID-19 (110 critically ill and 66 severely ill subjects at hospital admission and 106 follow-up samples) and in 32 non-COVID-19 severe sepsis patients. Associations between ACE2, inflammation-dependent biomarkers, pre-existing comorbidities, and clinical outcomes were studied. Results: Initial ACE2 activity was significantly higher in critically ill COVID-19 patients (54.4 [36.7-90.8] mU/L) than in severe COVID-19 (34.5 [25.2-48.7] mU/L; P

Following an intraventricular hemorrhage (IVH), red blood cell lysis and hemoglobin (Hb) oxidation with the release of heme can cause sterile neuroinflammation. In this study, we measured Hb derivates and cellular adhesion molecules ICAM-1 and VCAM-1 with cell-free miRNAs in cerebrospinal fluid (CSF) samples obtained from Grade-III and Grade-IV preterm IVH infants (IVH-III and IVH-IV, respectively) at multiple time points between days 0–60 after the onset of IVH. Furthermore, human choroid plexus epithelial cells (HCPEpiCs) were incubated with IVH and non-IVH CSF (10 v/v %) for 24 h in vitro to investigate the IVH-induced inflammatory response that was investigated via: (i) HMOX1, IL8, VCAM1, and ICAM1 mRNAs as well as miR-155, miR-223, and miR-181b levels by RT-qPCR, (ii) nuclear translocation of the NF-κB p65 subunit by fluorescence microscopy, and (iii) reactive oxygen species (ROS) measurement. We found a time-dependent alteration of heme, IL-8, and adhesion molecules which revealed a prolonged elevation in IVH-IV vs. IVH-III with higher miR-155 and miR-181b expression at days 41–60. Exposure of HCPEpiCs to IVH CSF samples induced HMOX1, IL8, and ICAM1 mRNA levels along with increased ROS production via the NF-κB pathway activation but without cell death, as confirmed by the cell viability assay. Additionally, the enhanced intracellular miR-155 level was accompanied by lower miR-223 and miR-181b expression in HCPEpiCs after CSF treatment. Overall, choroid plexus epithelial cells exhibit an abnormal cell phenotype after interaction with pro-inflammatory CSF of IVH origin which may contribute to the development of later clinical complications in preterm IVH.

Kinetic parameters of phenyl isocyanate–monoalcohol reactions has been studied using a microreactor system. The monoalcohol components were propan-1-ol, butan-1-ol, propan-2-ol and butan-2-ol. The reactions were conducted in alcohol/THF mixed solvent under pseudo-first-order circumstances at various temperatures. The reaction mixtures were analyzed by off-line HPLC. Reaction rate constants and apparent activation energies have been determined with good precision. The reaction rate constants were higher for the primary alcohols than for the secondary alcohols. Higher apparent activation energy was found for the secondary alcohols compared to the primary ones. The applied technique provides a simple way to study the effects of various factors (e.g. structure of the isocyanate and the alcohol, temperature, solvents, concentration of reagents, catalysis) on the kinetics of the isocyanate–alcohol reactions.

The use of medical diagnostics and therapeutic instruments supported by infocommunication systems is increasingly widespread. These devices are capable of conducting new telemedicine therapeutic methods, remote monitoring system and diagnostic procedures and may serve as additional tools for prevention, as well as health education. However, legal regulation of the area is very difficult owing to technological innovations and the emergence of new fields of application, but is nevertheless indispensable today. We strive to create an objective image that is typical of the current situation.

Cyclodextrins are widely used excipients for increasing water-solubility, delivery and bioavailability of lipophilic drugs. By using fluorescent cyclodextrin derivatives, we showed previously that cyclodextrins are able to enter Caco-2 intestinal cells by endocytosis, but the influence of different fluorescent labeling on the same cyclodextrin derivative has not been studied. The consequences of the cellular internalization of cyclodextrins have not been revealed yet either. The aims of this study were to compare the cellular internalization of fluorescein- and rhodamine-labeled (2-hydroxypropyl)-, (HPBCD) and randommethyl-&beta, cyclodextrins (RAMEB) and to investigate the intracellular effects of these derivatives on Caco-2 cells. Stimulation of the NF-kappa B pathway and autophagy and localization of these derivatives in lysosomes were tested. The endocytosis of these derivatives was examined by fluorescence microscopy and flow cytometry. Both fluorescein- and rhodamine-labeled derivatives entered the cells, therefore the type of the fluorescent labeling did not influence their internalization. Cyclodextrin pretreatment did not activate the translocation of the p65 subunit of the NF-kappa B heterodimer into the cell nuclei from the cytoplasm. After HPBCD or RAMEB treatment, formation of the autophagosomes did not increase compared to the control sample and at the same time these derivatives could be detected in lysosomes after internalization.

Highlights • Upregulated expression of ACE2 was recently reported in bronchoalveolar lavage fluid samples from COVID-19 patients. • We have first analyzed serum ACE2 activity in COVID-19 that increased about 40-fold over the normal range in the presence of 2-3-fold higher levels of endothelium biomarkers. • Soluble E-selectin followed the clinical status of our patient similarly to ferritin and IL-6 levels. • Based on the distinct time course of circulating ACE2, its dramatic rise may act as an endogenous nonspecific protective mechanism against SARS-CoV-2 infection that preceded the recovery of the patient., Endothelial cells express surface angiotensin converting enzyme 2 (ACE2), the main receptor for SARS-CoV-2 that promotes the infection of endothelial cells showing activation and damage. Bronchoalveolar lavage fluid from COVID-19 subjects showed a critical imbalance in the renin-angiotensin-aldosterone system with upregulated expression of ACE2. Recently, intravenous recombinant ACE2 was reported as an effective therapy in severe COVID-19 by blocking the viral entry to target cells. Here we present a case of a critically ill COVID-19 patient with acute respiratory distress syndrome where circulating ACE2 was first measured to monitor disease prognosis. ACE2 activity increased about 40-fold over the normal range and showed a distinct time course compared to 2-3-fold higher levels of endothelium biomarkers. Although the level of soluble E-selectin followed the clinical status of our patient similarly to ferritin and IL-6 levels, the dramatic rise in serum ACE2 activity may act as an endogenous nonspecific protective mechanism against SARS-CoV-2 infection that preceded the recovery of our patient.

Decreased human epididymis protein 4 (HE4) plasma levels were reported in cystic fibrosis (CF) patients under CFTR potentiator ivacaftor therapy, which inversely correlated with lung function improvement. In this study, we investigated whether HE4 expression was affected via modulation of CFTR function in CF bronchial epithelial (CFBE) cells in vitro. HE4 protein levels were measured in the supernatants of CFBE 41o− cells expressing F508del-CFTR or wild-type CFTR (wt-CFTR) after administration of lumacaftor/ivacaftor or tezacaftor/ivacaftor, while HE4 expression in CFBE 41o− cells were also analyzed following application of adenylate cyclase activators Forskolin/IBMX or CFTRinh172. The effect of all of these compounds on CFTR function was monitored by the whole-cell patch-clamp technique. Induced HE4 expression was studied with interleukin-6 (IL-6) in F508del-CFTR CFBE 41o− cells under TNF-α stimulation for 1 h up to 1 week in duration. In parallel, plasma HE4 was determined in CF subjects homozygous for p.Phe508del-CFTR mutation receiving lumacaftor/ivacaftor (Orkambi®) therapy. NF-κB-mediated signaling was observed via the nuclear translocation of p65 subunit by fluorescence microscopy together with the analysis of IL-6 expression by an immunoassay. In addition, HE4 expression was examined after NF-κB pathway inhibitor BAY 11-7082 treatment with or without CFTR modulators. CFTR modulators partially restored the activity of F508del-CFTR and reduced HE4 concentration was found in F508del-CFTR CFBE 41o− cells that was close to what we observed in CFBE 41o− cells with wt-CFTR. These data were in agreement with decreased plasma HE4 concentrations in CF patients treated with Orkambi®. Furthermore, CFTR inhibitor induced elevated HE4 levels, while CFTR activator Forskolin/IBMX downregulated HE4 in the cell cultures and these effects were more pronounced in the presence of CFTR modulators. Higher activation level of baseline and TNF-α stimulated NF-κB pathway was detected in F508del-CFTR vs. wt-CFTR CFBE 41o− cells that was substantially reduced by CFTR modulators based on lower p65 nuclear positivity and IL-6 levels. Finally, HE4 expression was upregulated by TNF-α with elevated IL-6, and both protein levels were suppressed by combined administration of NF-κB pathway inhibitor and CFTR modulators in CFBE 41o− cells. In conclusion, CFTR dysfunction contributes to abnormal HE4 expression via NF-κB in CF.

A kinetic and mechanistic investigation of the alcoholysis of phenyl isocyanate using 1-propanol as the alcohol was undertaken. A molecular mechanism of urethane formation in both alcohol and isocyanate excess is explored using a combination of an accurate fourth generation Gaussian thermochemistry (G4MP2) with the Solvent Model Density (SMD) implicit solvent model. These mechanisms were analyzed from an energetic point of view. According to the newly proposed two-step mechanism for isocyanate excess, allophanate is an intermediate towards urethane formation via six-centered transition state (TS) with a reaction barrier of 62.6 kJ/mol in the THF model. In the next step, synchronous 1,3-H shift between the nitrogens of allophanate and the cleavage of the C&ndash, N bond resulted in the release of the isocyanate and the formation of a urethane bond via a low-lying TS with 49.0 kJ/mol energy relative to the reactants. Arrhenius activation energies of the stoichiometric, alcohol excess and the isocyanate excess reactions were experimentally determined by means of HPLC technique. The activation energies for both the alcohol (measured in our recent work) and the isocyanate excess reactions were lower compared to that of the stoichiometric ratio, in agreement with the theoretical calculations.

Although the clinical outcomes of cystic fibrosis (CF) have been markedly improved through the recent implementation of novel CF transmembrane conductance regulator (CFTR) modulator drugs, robust and reliable biomarkers are still demanded for the early detection of CF lung disease progression, monitoring treatment efficacy and predicting life-threatening clinical complications. Thus, there is an unmet need to identify and validate novel, ideally blood based biomarkers with strong correlations to the severity of CF lung disease, which represents a major contribution to overall CF morbidity and mortality. In this review, we aim to summarize the utility of thus far studied blood-, sputum- and bronchoalveolar lavage (BAL)-based biomarkers to evaluate inflammatory conditions in the lung and to follow treatment efficacy in CF. Measurements of sweat chloride concentrations and the spirometric parameter FEV1 are currently utilized to monitor CFTR function and the effect of various CF therapies. Nonetheless, both have inherent pitfalls and limitations, thus routinely analyzed biomarkers in blood, sputum or BAL samples are required as surrogates for lung disorders. Recent discovery of new protein (e.g. HE4) and RNA-based biomarkers, such as microRNAs may offer a higher efficacy, which in aggregate may be valuable to evaluate disease prognosis and to substantiate CF drug efficacy.

Sepsis is a life-threating condition with dysregulated systemic host response to microbial pathogens leading to disproportionate inflammatory response and multi-organ failure. Various biomarkers are available for the diagnosis and prognosis of sepsis; however, these laboratory parameters may show limitations in these severe clinical conditions. MicroRNAs (miRNA) are single-stranded non-coding RNAs with the function of post-transcriptional gene silencing. They normally control numerous intracellular events, such as signaling cascade downstream of Toll-like receptors (TLRs) to avoid excessive inflammation after infection. In contrast, abnormal miRNA expression contributes to the development of sepsis correlating with its clinical features and outcomes. Based on recent clinical studies altered levels of circulating miRNAs can act as potential diagnostic and prognostic biomarkers in sepsis. In this review, we summarized the available data about TLR-mediated inflammatory signaling with its intracellular response in immune cells and platelets upon sepsis, which are, at least in part, under the regulation of miRNAs. Furthermore, the role of circulating miRNAs is also described as potential laboratory biomarkers in sepsis.

Several groups have demonstrated that induction of heme-oxygenase-1 (HO-1) could protect the myocardium against ischemic events; however, heme accumulation could lead to toxicity. The aim of the present study was to investigate the role of autophagy in heme toxicity. H9c2 cardiomyoblast cells were treated with different dose of hemin or cobalt-protoporphyrin IX (CoPP

Background We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy. Methods In this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1–6 months after commencement of ivacaftor, and were correlated with FEV1 (% predicted), sweat chloride, C-reactive protein (CRP) and body mass index (BMI). Results After 1 month of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6 months. A significant inverse correlation between absolute and delta values of HE4 and FEV1 (r = −0.5376; P Conclusions This study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy.

Catalytic activity of palladium catalysts with two different types of carbon support, Norit (an activated carbon), and bamboo-shaped carbon nanotubes (BCNT) have been tested for benzophenone hydrogenation. The selectivity toward the two possible reaction products (benzhydrol and diphenylmethane) can be directed by the catalyst support. It has been found that the Norit support preferred the over-hydrogenation of benzhydrol to diphenylmethane. The BCNT support proved to be much more selective and resulted as much as 99.3% benzhydrol selectivity at 96.3% benzophenone conversion. The high benzhydrol selectivity might be explained by the presence of covalently bonded nitrogen atoms in the catalyst (BCNT: 6.19 w/w%, Norit 0.54 w/w%) that can inhibit the over-hydrogenation process, thereby BCNTs are better catalyst supports for benzhydrol production than the commonly used activated carbon–supported catalysts.

Cystic fibrosis (CF) lung disease is characterized by the presence of neutrophils and released neutrophil extracellular traps (NETs). NETs are composed of a genomic DNA scaffold decorated with histones and neutrophil granule proteins. The long-term presence of NETs could lead to an autoimmune response in CF. This is supported by our published results showing elevated levels of anti-PAD4 autoantibodies in a U.S. CF cohort. To confirm and expand this observation, here we hypothesized that anti-PAD4 autoantibodies are also elevated in another CF cohort from Hungary, and additional, NET-targeting autoantibodies can be identified in CF. Fifty-seven CF patients (class I–III CFTR mutations, stable lung function, 26±−5.4 years of age (mean±SD), 54% female) and forty healthy subjects (26.2±3.6 years of age, 57% female) were recruited into this study in Hungary. Anti-PAD4 and anti-dsDNA autoantibodies were measured by ELISA while additional autoantibodies were determined by autoantigen microarray. Increased levels of anti-PAD4 autoantibodies were confirmed in this CF cohort. Serum levels of anti-dsDNA IgA autoantibodies were significantly higher in CF patients compared to control subjects. The autoantigen microarray analysis revealed significantly elevated levels of several, novel, NET-targeting autoantibodies in CF: anti-chromatin IgA, anti-core Histone IgA and IgE, anti-Histone H1 IgA, anti-Histone H2A IgA and IgM. No significant correlations of these autoantibodies with lung function (FEV1%pred), age or inflammatory markers (human epididymis protein 4, C-reactive protein) were found. Overall, these results indicate that chronic presence of NETs leads to a systemic autoimmune response in CF.

MicroRNAs (miRNA) are short, non-coding RNAs consisting of 18-25 nucleotides that regulate posttranscriptionally the gene expression involved in the regulation of physiological processes of the cells. Their key role is to modulate the translation of target mRNAs via binding to complementary sequences within the 3' UTRs of mRNAs resulting in altered protein synthesis or even the degradation of mRNAs. miRNAs are carried not only by cells with nucleus, but also in platelets, red blood cells, and they are present in the circulation, in urine and in other body fluids as well. The fact about functional miRNAs in platelets without nucleus having a half-life of 8-12 days was questioned for a long time, thus it was also obscure whether platelets are able to produce proteins de novo when being exposed to different challenges. In the last few years, several publications have described the expression and function of certain platelet mRNAs with their regulatory miRNAs in terms of regulation of cell activation, especially in diseases in which platelet activation status is elevated, such as in type 2 diabetes mellitus or in sepsis. Apart from their pathophysiological role, miRNAs may be applied as potential new biomarkers in the investigation or differential diagnosis of these clinical conditions. This review article sought to summarize the recent findings about platelet miRNAs focusing on their altered expression in diabetes and sepsis. Orv Hetil. 2018; 159(47): 1962-1970.Absztrakt: A mikro-RNS-ek (miRNS) rövid, általában 18–25 nukleotid hosszúságú, nem kódoló RNS-molekulák, melyek kulcsfontosságú szerepet játszanak a sejtek fiziológiás működéséhez szükséges gének expressziójának poszttranszkripciós szabályozásában. Fő funkciójuk a messenger RNS-ek (hírvivő RNS, mRNS) működésének modulálása azáltal, hogy az mRNS 3’ UTR-régiójához kötődnek, aminek eredményeként az mRNS által kódolt fehérje kifejeződése gátlódik, de akár az mRNS degradációja is bekövetkezhet. A miRNS-ek nemcsak maggal rendelkező sejtekben, de a vérlemezkékben, a vörösvértestekben, illetve keringő formában a vérben, a vizeletben és egyéb testfolyadékokban is megtalálhatók. Sokan sokáig kételkedve fogadták, hogy a sejtmaggal nem rendelkező keringő „sejtdarabok” a 8–12 napos átlagélettartamukkal hordozhatnak-e funkcionális RNS-molekulákat, és ezáltal képesek lehetnek-e akár fehérjeszintézisre különböző stimulusok hatására. Az elmúlt néhány évben számos közlemény jelent meg, amely bizonyította bizonyos vérlemezke-mRNS-ek és az azok működését reguláló miRNS-ek sejtaktivációt szabályozó szerepét olyan betegségekben is, melyekben a thrombocyták fokozott aktivációs állapotba kerülnek, például 2-es típusú diabetes mellitusban vagy szeptikus állapotban. Patofiziológiai szerepük mellett a miRNS-ek új biomarkerek is lehetnek ezen betegségek vizsgálatában vagy differenciáldiagnosztikájában. A jelen összefoglaló közlemény a thrombocyta-miRNS-ekről eddig ismeretes adatokat kívánta összegyűjteni, különös tekintettel a diabetesben és szepszisben leírt eltéréseivel. Orv Hetil. 2018; 159(47): 1962–1970.

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.In this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1-6 months after commencement of ivacaftor, and were correlated with FEVAfter 1 month of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6 months. A significant inverse correlation between absolute and delta values of HE4 and FEVThis study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy.

We previously found higher level of endothelial cell (EC) activation in patients who suffered from in-stent restenosis after bare-metal stenting compared to subjects who underwent drug-eluting stenting (DES) showing no complications. Here we investigated the potential transcriptional and post-transcriptional regulatory mechanisms by which everolimus attenuated EC activation after DES. We studied the effect of everolimus on E-selectin (SELE) and VCAM1 mRNA levels when human coronary artery (HCAECs) and human umbilical vein ECs were challenged with recombinant TNF-α (100 ng/mL) for 1-24 hours in the presence or absence of everolimus using 0.5 μM concentration locally maintained by DES. EC activation was evaluated via the levels of IL-1β and IL-6 mRNAs with miR-155 expression by RT-qPCR as well as the nuclear translocation of nuclear factor kappa beta (NF-κB) detected by fluorescence microscopy. To investigate the transcriptional regulation of E-selectin and VCAM-1, TNF-α-induced enhancer RNA (eRNA) expression at p65-bound enhancers in the neighboring genomic regions of SELE and VCAM1 genes, including SELE_-11Kb and VCAM1_-10Kb, were measured in HCAECs. Mature and precursor levels of E-selectin and VCAM-1 repressor miR-181b were quantified to analyze the post-transcriptional regulation of these genes in HCAECs. Circulating miR-181b was analyzed in plasma samples of stented subjects by stem-loop RT-qPCR. TNF-α highly elevated E-selectin and VCAM-1 expression at transcriptional level in ECs. Levels of mature, pre- and pri-miR-181b were repressed in ECs by TNF-α, while everolimus acted as a negative regulator of EC activation via inhibited translocation of NF-κB p65 subunit into cell nuclei, lowered eRNA expression at SELE and VCAM1 genes-associated enhancers and modulated expression of their post-transcriptional repressor miR-181b. Significant negative correlation was observed between plasma miR-181b and soluble E-selectin and VCAM-1 in patients. In conclusion, everolimus attenuates EC activation via reduced NF-κB p65 translocation causing decreased E-selectin and VCAM-1 expression at transcriptional and post-transcriptional level after DES.