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This study presents an exploration of the chemical space around derivatives of 3-benzamidopyrazine-2-carboxamides, previously identified as potent antimycobacterial compounds with predicted binding to mycobacterial prolyl-transfer RNA synthetase. New urea derivatives (Series-1) were generally inactive, probably due to their preference for cis-trans conformation (confirmed by density functional theory calculations and experimentally by nuclear overhauser effect spectroscopy NMR). Series-2 (3-benzamidopyrazine-2-carboxamides with disubstituted benzene ring) demonstrated that substituents larger than fluorine are not tolerated in the ortho position of the benzene ring. This series brought two new compounds (21: R = 2-F, 4-Cl and 22: R = 2-F, 4-Br) with in vitro activity against Mycobacterium tuberculosis H37Rv as well as multidrug-resistant clinical isolates, with minimum inhibitory concentration ranging from 6.25 to 25 µg/mL. The lactone-type derivatives 4H-pyrazino[2,3-d][1,3]oxazin-4-ones (Series-3) were inactive, but solvent stability studies of compound 29 indicated that they might be developed to usable lactone prodrugs of inhibitors of mycobacterial aspartate decarboxylase (PanD).
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Antituberculosos , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis , Relación Estructura-Actividad , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/enzimología , Antituberculosos/farmacología , Antituberculosos/química , Antituberculosos/síntesis química , Estructura Molecular , Aminoacil-ARNt Sintetasas/antagonistas & inhibidores , Aminoacil-ARNt Sintetasas/metabolismo , Pirazinas/farmacología , Pirazinas/química , Pirazinas/síntesis química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Relación Dosis-Respuesta a DrogaRESUMEN
We aimed to quantify rates of waning immunity after measles vaccination from seroprevalence data collected in a study of a population with high vaccination coverage and a fixed vaccination schedule. Data were collected during a national survey (the Immunological Survey) carried out in the Slovak Republic in 2018. The average rate of waning immunity against measles after the first dose of measles, mumps, and rubella (MMR) vaccine (ages 1.5-10 years) was 9.7% per year from the geometric mean titer value of 2,634 mUI/mL. The average waning rate after the second dose of MMR vaccine (ages 10-33 years) was significantly lower: 4.8% per year from the lower geometric mean titer of 1,331 mUI/mL. This decline in antibody levels suggests that vaccine-induced protection may be compromised and results in an increase in the proportion of seronegative/borderline individuals. These outcomes may provide a valuable source for critical assessment of direct and indirect effects of MMR vaccination.
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Sarampión , Paperas , Rubéola (Sarampión Alemán) , Humanos , Vacuna contra el Sarampión-Parotiditis-Rubéola , Rubéola (Sarampión Alemán)/epidemiología , Rubéola (Sarampión Alemán)/prevención & control , Estudios Seroepidemiológicos , Anticuerpos Antivirales , Sarampión/epidemiología , Sarampión/prevención & control , Paperas/epidemiología , Paperas/prevención & control , VacunaciónRESUMEN
In mass spectrometry (MS)-based metabolomics, there is a great need to combine different analytical separation techniques to cover metabolites of different polarities and apply appropriate multi-platform data processing. Here, we introduce AriumMS (augmented region of interest for untargeted metabolomics mass spectrometry) as a reliable toolbox for multi-platform metabolomics. AriumMS offers augmented data analysis of several separation techniques utilizing a region-of-interest algorithm. To demonstrate the capabilities of AriumMS, five datasets were combined. This includes three newly developed capillary electrophoresis (CE)-Orbitrap MS methods using the recently introduced nanoCEasy CE-MS interface and two hydrophilic interaction liquid chromatography (HILIC)-Orbitrap MS methods. AriumMS provides a novel mid-level data fusion approach for multi-platform data analysis to simplify and speed up multi-platform data processing and evaluation. The key feature of AriumMS lies in the optimized data processing strategy, including parallel processing of datasets and flexible parameterization for processing of individual separation methods with different peak characteristics. As a case study, Saccharomyces cerevisiae (yeast) was treated with a growth inhibitor, and AriumMS successfully differentiated the metabolome based on the augmented multi-platform CE-MS and HILIC-MS investigation. As a result, AriumMS is proposed as a powerful tool to improve the accuracy and selectivity of metabolome analysis through the integration of several HILIC-MS/CE-MS techniques.
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Metabolómica , Espectrometría de Masas en Tándem , Cromatografía Liquida/métodos , Metabolómica/métodos , Metaboloma , Electroforesis Capilar/métodosRESUMEN
The COVID-19 pandemic has affected the world and caused a supply shortage of personal protection equipment, especially filtering facepiece respirators (FFP). This has increased the risk of many healthcare workers contracting SARS-CoV-2. Various strategies have been assessed to tackle these supply issues. In critical shortage scenarios, reusing single-use-designed respirators may be required. Thus, an easily applicable and reliable FFP2 (or alike) respirator decontamination method, allowing safe re-use of FFP2 respirators by healthcare personnel, has been developed and is presented in this study. A potent and gentle aerosolized hydrogen peroxide (12% wt) method was applied over 4 hr to decontaminate various brands of FFP2 respirators within a small common room, followed by adequate aeration and storage overnight. The microbial efficacy was tested on unused respirator pieces using spores of Geobacillus stearothermophilus. Further, decontamination effectiveness was tested on used respirators after one 12-hr shift by swabbing before and after the decontamination. The effects of up to ten decontamination cycles on the respirators' functionality were evaluated using material properties, the structural integrity of the respirators, and fit tests with subjects. The suggested H2O2 decontamination procedure was proven to be (a) sufficiently potent (no microbial recovery, total inactivation of biological indicators as well as spore inoculum on critical respirator surfaces), (b) gentle as no significant damage to the respirator structural integrity and acceptable fit factors were observed, and (c) safe as no H2O2 residue were detected after the defined aeration and storage. Thus, this easy-to-implement and scalable method could overcome another severe respirator shortage, providing enough flexibility to draft safe, effective, and logistically simple crisis plans. However, as highlighted in this study, due to the wealth of design and material used in different models and brands of respirators, the decontamination process should be validated for each FFP respirator model before its field implementation.
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COVID-19 , SARS-CoV-2 , Humanos , Pandemias/prevención & control , COVID-19/prevención & control , Descontaminación/métodos , Equipo Reutilizado , Ventiladores MecánicosRESUMEN
In highly industrialized, densely populated parts of Central Europe, mobilization of legacy Zn pollution from forest ecosystems may negatively affect the quality of water resources. To test this hypothesis, we determined the 66Zn/64Zn isotope ratios of 15 Zn reservoirs and fluxes in an acidified, spruce die-back affected mountain-slope catchment in northern Czech Republic. The δ66Zn values of precipitation, organic horizon, and runoff were statistically indistinguishable. In contrast, δ66Zn values of bedrock orthogneiss and mineral soil were significantly different from δ66Zn values of runoff. The magnitude of within-site Zn isotope fractionations appeared to be relatively small. Despite the large potential source of Zn in bedrock, runoff exported mostly young pollutant Zn that had been temporarily stored in the organic horizon. This conclusion was corroborated by comparing Zn input-output mass balances in the polluted northern catchment and in a relatively unpolluted catchment situated 250 km to the south. Seven-times higher Zn export via runoff at the northern site was controlled by a combination of 10-times higher atmospheric Zn input and five-times higher DOC leaching, compared to the southern site. In industrial areas, atmospherically deposited Zn is leached from headwater catchments in a direct analogy to leaching of highly toxic pollutant Pb.
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Contaminantes Ambientales , Zinc , República Checa , Ecosistema , Monitoreo del Ambiente , Europa (Continente) , SueloRESUMEN
Gastrointestinal side effects of donepezil, including dyspepsia, nausea, vomiting or diarrhea, occur in 20-30% of patients. The pathogenesis of these dysmotility associated disorders has not been fully clarified yet. Pharmacokinetic parameters of donepezil and its active metabolite 6-O-desmethyldonepezil were investigated in experimental pigs with and without small intestinal injury induced by dextran sodium sulfate (DSS). Morphological features of this injury were evaluated by a video capsule endoscopy. The effect of a single and repeated doses of donepezil on gastric myoelectric activity was assessed. Both DSS-induced small intestinal injury and prolonged small intestinal transit time caused higher plasma concentrations of donepezil in experimental pigs. This has an important implication for clinical practice in humans, with a need to reduce doses of the drug if an underlying gastrointestinal disease is present. Donepezil had an undesirable impact on porcine myoelectric activity. This effect was further aggravated by DSS-induced small intestinal injury. These findings can explain donepezil-associated dyspepsia in humans.
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Donepezilo/farmacocinética , Tracto Gastrointestinal/patología , Tracto Gastrointestinal/fisiopatología , Indanos/metabolismo , Metaboloma , Complejo Mioeléctrico Migratorio , Piperidinas/metabolismo , Estómago/fisiopatología , Animales , Endoscopía Capsular , Sulfato de Dextran , Donepezilo/química , Donepezilo/farmacología , Femenino , Tracto Gastrointestinal/efectos de los fármacos , Metaboloma/efectos de los fármacos , Complejo Mioeléctrico Migratorio/efectos de los fármacos , Estómago/efectos de los fármacos , PorcinosRESUMEN
More than two decades after the discovery of adult neurogenesis in humans, researchers still struggle to elucidate the underlying transcriptional and post-transcriptional mechanisms. RNA interference is a crucially important process in the central nervous system, and its role in adult neurogenesis is poorly understood. In this work, we address the role of Dicer-dependent microRNA biogenesis in neuronal differentiation of adult neural stem cells within the subventricular zone of the mouse brain. Loss of the Dicer1 gene in the tailless (Tlx)-positive cells did not cause the decline in their numbers, but severely affected differentiation. Thus, our findings identify yet another phenomenon associated with microRNA pathway deregulation in adult neural stem cells which might be of relevance both for neuroscience and clinical practice.
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Proliferación Celular , MicroARNs/genética , Células-Madre Neurales/citología , Neurogénesis , Células Madre Adultas/citología , Células Madre Adultas/metabolismo , Animales , Células Cultivadas , ARN Helicasas DEAD-box/genética , Femenino , Regulación del Desarrollo de la Expresión Génica , Ventrículos Laterales/citología , Ventrículos Laterales/metabolismo , Masculino , Ratones , Células-Madre Neurales/metabolismo , Ribonucleasa III/genética , TranscriptomaRESUMEN
The present paper describes the development of a prosthetic hand based on human hand anatomy. The hand phalanges are printed with 3D printing with Polylactic Acid material. One of the main contributions is the investigation on the prosthetic hand joins; the proposed design enables one to create personalized joins that provide the prosthetic hand a high level of movement by increasing the degrees of freedom of the fingers. Moreover, the driven wire tendons show a progressive grasping movement, being the friction of the tendons with the phalanges very low. Another important point is the use of force sensitive resistors (FSR) for simulating the hand touch pressure. These are used for the grasping stop simulating touch pressure of the fingers. Surface Electromyogram (EMG) sensors allow the user to control the prosthetic hand-grasping start. Their use may provide the prosthetic hand the possibility of the classification of the hand movements. The practical results included in the paper prove the importance of the soft joins for the object manipulation and to get adapted to the object surface. Finally, the force sensitive sensors allow the prosthesis to actuate more naturally by adding conditions and classifications to the Electromyogram sensor.
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Miembros Artificiales , Mano , Dedos , Fuerza de la Mano , Humanos , Diseño de Prótesis , TendonesRESUMEN
Chemicals added in personal care products are of emerging concern because their fate and their effect on the environment is not completely known. Benzotriazole UV stabilizers (BUVSs) are compounds used in different cosmetic products, which may reach the marine environment through marine discharge from treated waters or directly from bathing areas. Once released into the aquatic ecosystem, BUVSs can be bioaccumulated by aquatic organisms. To identify the human exposure risk, it is important to have suitable analytical methods to determine the presence of BUVSs in these organisms. Because of the complexity of such a biological matrix, selective extraction and detection techniques are required to isolate and quantify these kinds of pollutants at trace levels. In the present work, we optimized a method based on microwave-assisted extraction combined with ultra-high performance liquid chromatography and mass spectrometry detection to determine six benzotriazole compounds in fish samples. The absolute extraction yields provided by the proposed method were higher than 40% for most compounds, with intra-day and inter-day relative standard deviations ranging from 0.27 to 6.06 and 1.12-21.3%, respectively. The limits of quantification were in the range of 1.13-9.66 ng g-1 (dry weight). The method was applied to the study of three species of fish (Boops boops, Sphyraena viridensis, Sphoeroides marmoratus) that were collected close to three marine outfalls of treated waters on the Gran Canaria Island (Spain) for two years. Four of the six studied compounds, UV-326, UV-328, UV-329 and UV-360, were found with concentrations ranging from 1.34 ng g-1 to 45.6 ng g-1 (dry weight).
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Espectrometría de Masas en Tándem , Contaminantes Químicos del Agua , Animales , Ecosistema , Peces , España , TriazolesRESUMEN
"Comparison of nitrogen inputs and accumulation in 210 Pb-dated peat cores: Evidence for biological N2 -fixation in Central European peatlands despite decades of atmospheric N pollution" https://doi.org/10.1111/gcb.14505, by Martin Novak, Melanie A. Vile, Jan Curik, Bohuslava Cejkova, Jiri Barta, Marketa Stepanova, Ivana Jackova, Frantisek Buzek, Leona Bohdalkova, Eva Prechova, Frantisek Veselovsky, Marie Adamova, Ivana Valkova and Arnost Komarek. The above article, first published online in Wiley Online Library (wileyonlinelibrary.com) in Global Change Biology, has been retracted by agreement between the authors, the journal Editor-in-Chief, Stephen P. Long, and John Wiley & Sons Ltd. Since publication of the above article, it was brought to the attention of the authors that the peat accretion rates violate reasonable ranges of peatland C/N/P stoichiometry, placing the quantitative conclusions of the article in serious error. The authors apologize for any inconvenience the publication of this work may have caused our readers. REFERENCE Novak, M., Vile, M. A., Cejkova, B., Barta, J., Stepanova, M., Jackova, I., Buzek, F., Bohdalkova, L., Prechova, E., Veselovsky, F., Adamova, M., Valkova, I., & Komarek, A. (2018). Comparison of nitrogen inputs and accumulation in 210 Pb-dated peat cores: Evidence for biological N2 -fixation in Central European peatlands despite decades of atmospheric N pollution. Global Change Biology.. https://doi.org/10.1111/gcb.14505.
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Necrophagous beetles of genus Thanatophilus are well recognized as a group of beetles with a high potential utility in forensic entomology. They can be used to estimate postmortem interval (PMI) or validate the value for other groups of insects commonly encountered on human remains, like blowflies (Calliphoridae). However, reliable tools for instar and species identification of their larvae are needed as such information is crucial for allowing accurate PMI estimate. One of the most common species of the genus Thanatophilus in Europe is Thanatophilus sinuatus. This species occurs frequently on human remains and its larvae feed on decaying tissues throughout their development. Therefore, the larvae could become useful bioindicators for forensic entomology, although their current description does not allow reliable instar or species identification. Our goal was to provide morphological characters for species and instar identification of all larval stages of T. sinuatus. The larvae were obtained from laboratory rearing under controlled conditions (20 °C and 16:8 h of light/dark period). Qualitative and quantitative morphological instar and species-specific characters are described and illustrated. Additionally, we report observations of biological and developmental lengths for all stages of the species. We also compared these morphological characters with recent description of T. rugosus and provided an identification key of these two similar and often co-occurring species. We noticed that some characters for instar identification were shared between T. sinuatus and T. rugosus and were confirmed by comparison with larvae of T. dentigerus that they can be applied to other species of the genus.
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Escarabajos/clasificación , Escarabajos/crecimiento & desarrollo , Entomología Forense , Larva/crecimiento & desarrollo , Pupa/crecimiento & desarrollo , Animales , Estudios de Evaluación como Asunto , Conducta Alimentaria , Larva/clasificación , Microscopía Electrónica de Rastreo , Imagen Óptica , Pupa/clasificaciónRESUMEN
OBJECTIVE: The aim of the study was to analyse the occurrence of lead in selected samples of fruit distilled spirits for own consumptions in terms of possible contribution to the occurrence of alcohol-attributable diseases. METHODS: In a pilot study, we analysed 18 samples of fruit spirits for own consumption. Most of the samples were distilled in the local growing distilleries in the Zilina Region with exception of 3 samples collected in the Trnava Region (one of them was of Hungarian origin). Sample preparation included previous mineralization with use of microwave decomposition system Multiwave 60 50 Hz. The samples were analysed by atomic absorption spectroscopy with graphic furnace (AAS GBC XplorAA 5000 with GF 5000). RESULTS: The average ethanol level in our samples was higher in comparison with distributed spirits. We detected lead in all samples. In two of them the concentration was lower than the limit of quantitation (LOQ). The highest lead concentrations were observed in plum spirit from Hungary (581.0 µg/l), and in grape spirit made in the Trnava Region (466.3 µg/l). CONCLUSIONS: Lead is a widespread contaminant of fruit spirits prepared for own consumption. Taking into consideration its common occurrence and possible multiplicative effect with ethanol, we can assume that lead can contribute to the occurrence of several alcohol-attributable chronic diseases. Due to the insufficient information in this field, our results provide significant insight into the issue and present an important starting point for further research.
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Bebidas Alcohólicas/análisis , Contaminación de Alimentos/análisis , Manipulación de Alimentos , Frutas/química , Plomo , Manipulación de Alimentos/métodos , Humanos , Hungría , Proyectos Piloto , Salud PúblicaRESUMEN
Recent work has identified a bis-(p-nitrophenyl)ureidodecalin anion carrier as a promising candidate for biomedical applications, showing good activity for chloride transport in cells yet almost no cytotoxicity. To underpin further development of this and related compounds, a detailed structural and binding investigation is reported. Crystal structures of the transporter as five solvates confirm the diaxial positioning of urea groups while revealing a degree of conformational flexibility. Structures of complexes with Cl- , Br- , NO3- , SO42- and AcO- , supported by computational studies, show how the binding site can adapt to accommodate these anions. 1 Hâ NMR binding studies revealed exceptionally high affinities for anions in DMSO, decreasing in the order SO42- >H2 PO4- ≈HCO3- ≈AcO- â«HSO4- >Cl- >Br- >NO3- >I- . Analysis of the binding results suggests that selectivity is determined mainly by the H-bond acceptor strength of different anions, but is also modulated by receptor geometry.
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Aniones/química , Cloruros/química , Nitrofenoles/química , Urea/química , Sitios de Unión , Computadores Moleculares , Cristalografía por Rayos X , Espectroscopía de Resonancia Magnética , Conformación MolecularRESUMEN
Determination of insect species and their instars, occurring on human remains, is important information that allows us to use insects for estimation of postmortem interval and detect possible manipulation with the body. However, larvae of many common species can be identified only by molecular methods, which is not always possible. The instar determination is even more challenging, and qualitative characters that would allow a more precise identification are mostly unknown. Thanatophilus rugosus (Linnaeus, 1758) is a common necrophagous beetle in the whole Palaearctic region from Europe to Japan. The species is often encountered on corpses of large vertebrates including humans, and its potential to become a useful bioindicator for forensic entomology is therefore high. Adults can be easily distinguished from other species; however, larvae were never thoroughly described to allow species and instar identification. The aim of this study was to provide reliable morphological characters that would allow species and instar identification of T. rugosus larvae. The material for morphological study was obtained from rearing under controlled conditions (20 °C and 12:12 h of light/dark period), and specimens that were not studied morphologically were allowed to complete their development. Quantitative and qualitative morphological characters for instar and species identification are described and illustrated. Additionally, we report observations of biology and developmental length for all stages of the species.
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Escarabajos/crecimiento & desarrollo , Larva/crecimiento & desarrollo , Animales , Ciencias Forenses , Microscopía Electrónica de Rastreo , Imagen ÓpticaRESUMEN
The potential of paramagnetic ruthenium(III) compounds for use as anticancer metallodrugs has been investigated extensively during the past several decades. However, the means by which these ruthenium compounds are transported and distributed in living bodies remain relatively unexplored. In this work, we prepared several novel ruthenium(III) compounds with the general structure Na+[ trans-RuIIICl4(DMSO)(L)]- (DMSO = dimethyl sulfoxide), where L stands for pyridine or imidazole linked with adamantane, a hydrophobic chemophore. The supramolecular interactions of these compounds with macrocyclic carriers of the cyclodextrin (CD) and cucurbit[ n]uril (CB) families were investigated by NMR spectroscopy, X-ray diffraction analysis, isothermal titration calorimetry, and relativistic DFT methods. The long-range hyperfine NMR effects of the paramagnetic guest on the host macrocycle are related to the distance between them and their relative orientation in the host-guest complex. The CD and CB macrocyclic carriers being studied in this account can be attached to a vector that attracts the drug-carrier system to a specific biological target and our investigation thus introduces a new possibility in the field of targeted delivery of anticancer metallodrugs based on ruthenium(III) compounds.
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Hidrocarburos Aromáticos con Puentes/química , Complejos de Coordinación/química , Ciclodextrinas/química , Portadores de Fármacos/química , Imidazoles/química , Rutenio/química , Adamantano/análogos & derivados , Adamantano/síntesis química , Adamantano/química , Anisotropía , Antineoplásicos/síntesis química , Antineoplásicos/química , Hidrocarburos Aromáticos con Puentes/síntesis química , Espectroscopía de Resonancia Magnética con Carbono-13 , Complejos de Coordinación/síntesis química , Ciclodextrinas/síntesis química , Portadores de Fármacos/síntesis química , Imidazoles/síntesis química , Espectroscopía de Protones por Resonancia Magnética , Piridinas/síntesis química , Piridinas/química , Teoría Cuántica , Espectrometría de Masa por Ionización de Electrospray , Difracción de Rayos XRESUMEN
State-of-the-art computations combined with Ziegler-Rauk energy decomposition analyses are employed to introduce a new class of anti-electrostatic ion-σ bonds with considerable stability and a substantial contribution from charge transfer and dispersion between ions and finite-size functionalized graphane flakes, G-XYs. G-XYs have diverse electric multipolar moments that are comparable with those of newly synthesized all-cis-hexa-halocyclohexanes. The strong, long-range electrostatic and Pauli repulsions between some G-XYs and certain ions induce a gas-phase energy barrier to the physisorption of ions on the surface of G-XYs. However, the repulsive interactions can be overbalanced by the strong orbital interactions operating in the formation of ion-σ complexes at short range, leading to covalent-type intermolecular bonds as strong as -34â kcal mol-1 .
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Supramolecular interactions are generally classified as noncovalent. However, recent studies have demonstrated that many of these interactions are stabilized by a significant covalent component. Herein, for systems of the general structure [MX6 ]2- :YX2 (M=Se or Pt; Y=S, Se, or Te; X=F, Cl, Br, I), featuring bifurcated chalcogen bonding, it is shown that, although electrostatic parameters are useful for estimating the long-range electrostatic component of the interaction, they fail to predict the correct order of binding energies in a series of compounds. Instead, the Lewis basicity of the individual substituents X on the chalcogen atom governs the trends in the binding energies through fine-tuning the covalent character of the chalcogen bond. The effects of substituents on the binding energy and supramolecular electron sharing are consistently identified by an arsenal of theoretical methods, ranging from approaches based on the quantum chemical topology to analytical tools based on the localized molecular orbitals. The chalcogen bonding investigated herein is driven by orbital interactions with significant electron sharing; this can be designated as supramolecular covalence.
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We present a case report of a patient relapsing after anti-CD38 treatment (daratumumab). The phenotype of the disease changed during this treatment, and the myeloma clone became CD38 negative and daratumumab refractory. We expected clonal shift, however, based on immunophenotyping, cytogenetics and arrayCGH; the clone was identical as before daratumumab-based treatment with the exception of CD38 negativity. We suggest that the downregulation or loss of CD38 might be an epigenetic "escape mechanism" of malignant plasma cells from antibody-based treatment. The aim of our study was to point out the pitfalls of immunophenotyping and cytogenetics in both assessing the minimal residual disease and clone detection after monoclonal antibody-based therapy.
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Mieloma Múltiple/diagnóstico , Mieloma Múltiple/metabolismo , ADP-Ribosil Ciclasa 1/antagonistas & inhibidores , ADP-Ribosil Ciclasa 1/metabolismo , Anticuerpos Monoclonales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores , Hibridación Genómica Comparativa , Análisis Citogenético , Humanos , Inmunofenotipificación , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Pronóstico , RecurrenciaRESUMEN
The article looks at the accessibility of health care in the Czech republic in relation to the relevant legislation. Health care access is a frequently debated issue, but quantifying it is a difficult task. There are no official regulations in our country for determining the capacity of health care workers by category and type of health care provision that could be used to ensure health care is accessible to the inhabitants of a given region. Nonetheless, a government regulation came into force in 2013 regulating local health care access and travel time. This regulation is the first of its kind in the Czech rep., but (perhaps because of this) it contains a number of ambiguities, and this lack of detail makes it impossible to ensure the regulation is fully implemented and adhered to.The aim of this article is to attempt to identify these ambiguities and to broadly pinpoint the main factors potentially affecting health care access. To achieve this, an analysis is performed on the data on health care providers and methods using advanced GIS (geographic information systems) are utilized. Given the wide range of health care services on offer, the examples relate to primary health care, specifically practical medicine for children and adolescents.
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Accesibilidad a los Servicios de Salud , Adolescente , Servicios de Salud del Adolescente , Niño , Servicios de Salud del Niño , República Checa , HumanosRESUMEN
In this work we investigated the influence of an external electric field on the arrangement of the solvent shells around ions interacting with a carbon-based receptor. Our survey reveals that the mechanism of interaction between a monoatomic ion and a π-type ion receptor varies by the variation in the solvent polarity, the nature of the ion, and the strength of the external field. The characteristics of the ion-surface interaction in nonpolar solvents are similar to those observed in a vacuum. However, in water, we identified two mechanisms. Soft and polarizable ions preferentially interact with the π-receptor. In contrast, two bonded states were found for hard ions. A fully solvated ion, weakly interacting with the receptor at weak field, and a strong π-complex at the strong-field regime were identified. An abrupt variation in the potential energy surface (PES) associated with the rearrangement of the solvation shell on the surface of the receptor induced by an external field was observed both in implicit and explicit solvent environments. The electric field at which the solvation shell breaks is proportional to the hardness of the ion as has been suggested recently based on experimental observations.