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Routine analysis of inorganic analytes in whole water samples from rivers (unfiltered river water) is rarely reported in scientific publications. However, this sample type is valuable and often used in long-term monitoring, regulation, and catchment element budgets, as it includes the dissolved, colloidal, and particulate fraction in one sample type. Preservation measures are not needed and solid-liquid partitioning can be disregarded, which simplifies automated sampling and storage procedures. In this study, we provide several digestion protocols for whole water samples from rivers and the subsequent multi-element analysis of 67 major, minor, and trace elements: Li, Be, B, Na, Mg, Al, Si, P, S, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, Ge, As, Se, Br, Rb, Sr, Y, Zr, Nb, Mo, Ru, Ag, Cd, In, Sn, Sb, Te, Cs, Ba, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Hf, Ta, W, Ir, Pt, Au, Hg, Tl, Pb, Bi, Th, U. In the absence of whole water reference materials for inorganic analytes, we introduce simulated whole water samples by suspending sediment reference materials as quality control measures. The applicability for improved routine water quality monitoring was successfully tested on samples from different rivers revealing variations of the element fingerprints over time.
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The metabolism of malignant cells differs significantly from that of healthy cells and thus, it is possible to perform metabolic imaging to reveal not only the exact location of a tumor, but also intratumoral areas of high metabolic activity. Herein, we demonstrate the feasibility of metabolic tumor imaging using signal-enhanced 1-13 C-pyruvate-d3 , which is rapidly enhanced via para-hydrogen, and thus, the signal is amplified by several orders of magnitudes in less than a minute. Using as a model, human melanoma xenografts injected with signal-enhanced 1-13 C-pyruvate-d3, we show that the conversion of pyruvate into lactate can be monitored along with its kinetics, which could pave the way for rapidly detecting and monitoring changes in tumor metabolism.
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Neoplasias , Ácido Pirúvico , Humanos , Ácido Pirúvico/metabolismo , Hidrogênio , Imageamento por Ressonância Magnética/métodos , Isótopos de CarbonoRESUMO
OBJECTIVES: Dance as a non-pharmacological therapy is commonly used in dementia care, although the evidence of its effects remains unclear. This study systematically reviewed the effects of dance interventions on neuropsychiatric symptoms (NPS) in people living with dementia. To systematically identify and evaluate dance interventions, a standardized terminology for Dance-Specific Activity (DSA) is proposed. METHODS: Literature search was conducted on electronic databases until April 30th 2021. Studies were included when they quantified the effects of DSA on NPS in people with clinical diagnosis of dementia. Included studies were analyzed in detail for NPS. Study quality was assessed by PEDro scale (German version). RESULTS: 4 studies were included. The studies differed in study design, intervention protocols, dance styles, or measurement tools, and were generally of low study quality. Two trials showed improvements in NPS and 2 trials showed no exacerbation of NPS after DSA. CONCLUSIONS: The results of the 4 available trials indicate a positive tendency towards the effects of DSA, but considering the limitations of the few available studies, a clear statement about the effects of DSA is not possible yet. Based on the included trials, the following implications for clinical research and routine care can be derived: (1) DSA seems to be a practical terminology for identifying dance interventions (2) DSA seems to be a safe intervention for people living with dementia. (3) Different dance styles can be used. (4) DSA approaches should be better structured by differentiating between the domains type, content, intention, and protocol of the intervention.
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Dança , Demência , Humanos , Demência/complicações , Demência/terapia , Demência/psicologiaRESUMO
Noonan syndrome patients harboring causative variants in LZTR1 are particularly at risk to develop severe and early-onset hypertrophic cardiomyopathy. In this study, we investigate the mechanistic consequences of a homozygous variant LZTR1L580P by using patient-specific and CRISPR-Cas9-corrected induced pluripotent stem cell (iPSC) cardiomyocytes. Molecular, cellular, and functional phenotyping in combination with in silico prediction identify an LZTR1L580P-specific disease mechanism provoking cardiac hypertrophy. The variant is predicted to alter the binding affinity of the dimerization domains facilitating the formation of linear LZTR1 polymers. LZTR1 complex dysfunction results in the accumulation of RAS GTPases, thereby provoking global pathological changes of the proteomic landscape ultimately leading to cellular hypertrophy. Furthermore, our data show that cardiomyocyte-specific MRAS degradation is mediated by LZTR1 via non-proteasomal pathways, whereas RIT1 degradation is mediated by both LZTR1-dependent and LZTR1-independent pathways. Uni- or biallelic genetic correction of the LZTR1L580P missense variant rescues the molecular and cellular disease phenotype, providing proof of concept for CRISPR-based therapies.
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Células-Tronco Pluripotentes Induzidas , Miócitos Cardíacos , Síndrome de Noonan , Proteínas ras , Humanos , Síndrome de Noonan/genética , Síndrome de Noonan/patologia , Síndrome de Noonan/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/patologia , Proteínas ras/metabolismo , Proteínas ras/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Mutação/genética , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Hipertrófica/metabolismo , Polimerização , Sistemas CRISPR-Cas/genética , Proteólise , Mutação de Sentido Incorreto , Multimerização Proteica , Genes Recessivos , FenótipoRESUMO
The oxygen-evolving complex (OEC) in photosystem II (PS II) was studied in the S0 through S3 states using 1s2p resonant inelastic X-ray scattering spectroscopy. The spectral changes of the OEC during the S-state transitions are subtle, indicating that the electrons are strongly delocalized throughout the cluster. The result suggests that, in addition to the Mn ions, ligands are also playing an important role in the redox reactions. A series of Mn(IV) coordination complexes were compared, particularly with the PS II S3 state spectrum to understand its oxidation state. We find strong variations of the electronic structure within the series of Mn(IV) model systems. The spectrum of the S3 state best resembles those of the Mn(IV) complexes Mn3(IV)Ca2 and saplnMn2(IV)(OH)2. The current result emphasizes that the assignment of formal oxidation states alone is not sufficient for understanding the detailed electronic structural changes that govern the catalytic reaction in the OEC.
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Manganês/química , Compostos Organometálicos/química , Oxigênio/química , Complexo de Proteína do Fotossistema II/química , Biocatálise , Elétrons , Estrutura Molecular , Compostos Organometálicos/metabolismo , Complexo de Proteína do Fotossistema II/metabolismoRESUMO
The protonation state of oxo bridges in nature is of profound importance for a variety of enzymes, including the Mn4CaO5 cluster of photosystem II and the Mn2O2 cluster in Mn catalase. A set of dinuclear bis-µ-oxo-bridged Mn(IV) complexes in different protonation states was studied by Kß emission spectroscopy to form the foundation for unraveling the protonation states in the native complex. The valence-to-core regions (valence-to-core XES) of the spectra show significant changes in intensity and peak position upon protonation. DFT calculations were performed to simulate the valence-to-core XES spectra and to assign the spectral features to specific transitions. The Kß(2,5) peaks arise primarily from the ligand 2p to Mn 1s transitions, with a characteristic low energy shoulder appearing upon oxo-bridge protonation. The satellite Kß" peak provides a more direct signature of the protonation state change, since the transitions originating from the 2s orbitals of protonated and unprotonated µ-oxo bridges dominate this spectral region. The energies of the Kß" features differ by ~3 eV and thus are well resolved in the experimental spectra. Additionally, our work explores the chemical resolution limits of the method, namely, whether a mixed (µ-O)(µ-OH2) motif can be distinguished from a symmetric (µ-OH)2 one. The results reported here highlight the sensitivity of Kß valence-to-core XES to single protonation state changes of bridging ligands, and form the basis for further studies of oxo-bridged polymetallic complexes and metalloenzyme active sites. In a complementary paper, the results from X-ray absorption spectroscopy of the same Mn(IV) dimer series are discussed.
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Complexos de Coordenação/química , Manganês/química , Metaloproteínas/química , Oxigênio/química , Modelos Moleculares , Oxirredução , Complexo de Proteína do Fotossistema II/química , Prótons , Espectrometria por Raios XRESUMO
Triple-quadrupole inductively coupled plasma mass spectrometry (ICP-QQQ-MS) is a unique analytical technique which is, next to speciation analyses, applied for the determination of total element concentrations in several matrices. Due to its wide linear range, short analysis times, and the collision-reaction gas technology, it is capable of addressing a high number of analytes in a single run with sufficient low limits of quantification for river water monitoring. Over the last decades, the focus of the environmental monitoring changed from "traditional" and regulated analytes to elements of possibly rising concern from new applications such as the so-called technology-critical elements (TCE). By widening the analytical window of this method for applications in networks of future river water monitoring, a better understanding of natural transport processes and global biogeochemical element cycles will be established and the total number of methods can be reduced. During method development and validation, certified reference materials, calibration check solutions, and spiked river water samples from 12 major German rivers covering different catchment areas were measured and evaluated with the three cell gases He, H2 and O2. The method delivers a best as possible undisturbed simultaneous determination for 68 out of 71 target analytes with recoveries in an accepted range of 80-120% for river water samples (dissolved fraction; <0.45 µm). After comprehensive evaluation, we offer a novel best-practice multi-element method for river water monitoring with the goal of fostering the exchange and discussion between practitioners in long-term river monitoring. It enables the readers to create their own methods based on the scientific needs to monitor elemental "fingerprints" of rivers and their catchments.
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Rios , Poluentes Químicos da Água , Rios/química , Água Doce , Gases/análise , Monitoramento Ambiental/métodos , Água/análise , Poluentes Químicos da Água/análiseRESUMO
OBJECTIVE: To identify and analyze the components applied in interventions using physical activity (PA) monitoring in geriatric patients and determine their feasibility and applicability. METHODS: A systematic search in six databases (PubMed, Embase, SPORTDiscus, CINAHL, Web of Science, and GeroLit) was conducted to identify studies reporting interventions that included the application of a PA monitor in adults aged ≥ 60 years with a clinical diagnosis. PA monitor interventions were analyzed regarding their feedback, goal-setting and behavior change technique (BCT) components. To determine the feasibility and applicability of interventions, the participants' adherence to the intervention, their experience as well as adverse events were analyzed. RESULTS: Seventeen eligible studies, applying 22 interventions, were identified. Studies included a total of 827 older patients with a median age of 70.2 years. In thirteen interventions (59%), the PA monitor was embedded in a structured behavioral intervention, an indication-specific intervention or usual care. Most frequently applied intervention components were goal setting and self-monitoring (n = 18), real-time PA monitor feedback complemented by feedback from the study team (n = 12), use of further BCTs (n = 18), and regular counseling with the study team (n = 19). Comprehensive information on the participants' intervention adherence and experience were reported for 15 (68%) and 8 (36%) interventions, respectively. CONCLUSION: The components included in PA monitoring-based interventions varied considerably especially regarding the extent, frequency, and content of feedback, goal setting and BCTs counseling. Future research should evaluate which components are most effective and clinically applicable to promote physical activity in geriatric patients. To be able to precisely analyze the effects, trials should seek to report details on intervention components, adherence and adverse events, while future reviews may use the findings of this scoping review to conduct analyses with less heterogeneity in study characteristics and intervention strategies.
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Suspended particulate matter (SPM) plays a major role in nutrient cycles and for the transport of pollutants within local and transboundary water catchments. Obtaining representative SPM samples from rivers, lakes, inland and coastal waters is crucial for quantitative and qualitative chemical analyses to correctly describe the chemical status of a water body. However, a representative sampling of SPM over time is challenging due to the heterogeneity of SPM particles sizes, their non-uniform distribution in rivers, and a variety of sampling devices being in use. Therefore, we investigated the efficiencies of five different sampling devices commonly used in national and international monitoring programs to collect representative SPM samples. We tested three passive sedimentation-based samplers (SBSs: sedimentation box, SB; sedimentation tank, ST; Raetz Sampler, RS), and two active separation techniques (continuous flow centrifuge, CFC; vacuum filtration, VF) in an experimental laboratory setup using in-house SPM standard suspensions (mineral, organic, and microplastic particles) with defined particle sizes. The mass-based efficiencies of the three examined SBSs were 0-66% for the mineral and organic particles <75 µm, where the mean particle sizes of collected samples were always shifted to bigger sizes compared to the initial suspensions. The efficiencies of the three SBSs to collect microplastic particles <80 µm were <20% due to the lower densities of microplastic compared to organic and mineral particles. In contrast to the SBSs, VF and CFC units showed excellent efficiencies >86% for all tested materials, with similar particle size distributions of the sampled material compared to those of the inlet suspensions. In conclusion, SPM sampling efficiencies of sampling units have to be carefully considered and compared to the respective aims of the monitoring approaches, especially when statements are derived from quantitative results on SPM.
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Material Particulado , Poluentes Químicos da Água , Material Particulado/análise , Microplásticos , Plásticos , Suspensões , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Rios , Água/análiseRESUMO
Nimodipine prevents cerebral vasospasm and improves functional outcome after aneurysmal subarachnoid hemorrhage (aSAH). The beneficial effect is limited by low oral bioavailability of nimodipine, which resulted in an increasing use of nanocarriers with sustained intrathecal drug release in order to overcome this limitation. However, this approach facilitates only a continuous and not an on-demand nimodipine release during the peak time of vasospasm development. In this study, we aimed to assess the concept of controlled drug release from nimodipine-loaded copolymers by ultrasound application in the chicken chorioallantoic membrane (CAM) model. Nimodipine-loaded copolymers were produced with the direct dissolution method. Vasospasm of the CAM vessels was induced by means of ultrasound (Physiomed, continuous wave, 3 MHz, 1.0 W/cm2). The ultrasound-mediated nimodipine release (Physiomed, continuous wave, 1 MHz, 1.7 W/cm2) and its effect on the CAM vessels were evaluated. Measurements of vessel diameter before and after ultrasound-induced nimodipine release were performed using ImageJ. The CAM model could be successfully carried out in all 25 eggs. After vasospasm induction and before drug release, the mean vessel diameter was at 57% (range 44-61%) compared to the baseline diameter (set at 100%). After ultrasound-induced drug release, the mean vessel diameter of spastic vessels increased again to 89% (range 83-91%) of their baseline diameter, which was significant (p = 0.0002). We were able to provide a proof of concept for in vivo vasospasm induction by ultrasound application in the CAM model and subsequent resolution by ultrasound-mediated nimodipine release from nanocarriers. This concept merits further evaluation in a rat SAH model.
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Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Animais , Micelas , Nimodipina , Ratos , Ultrassonografia , Vasodilatadores , Vasoespasmo Intracraniano/diagnóstico por imagem , Vasoespasmo Intracraniano/tratamento farmacológico , Vasoespasmo Intracraniano/etiologiaRESUMO
Cerebral vasospasm is a highly investigated phenomenon in neurovascular research. Experimental vasospasm models are irreplaceable for the evaluation of new antivasospastic drugs. In this study, we assessed the reliability of in vivo vasospasm induction by ultrasound application in the chicken chorioallantoic membrane (CAM) model. After incubation of fertilized chicken eggs for four days, a fenestration was performed to enable examination of the CAM vessels. On the thirteenth day, continuous-wave ultrasound (3 MHz, 1 W/cm2) was applied on the CAM vessels for 60 s. The ultrasound effect on the vessels was recorded by life imaging (5-MP HD-microscope camera, Leica®). The induced vessel diameter changes were evaluated in a defined time interval of 20 min using a Fiji macro. The vessel diameter before and after sonication was measured and the relative diameter reduction was determined. A first reduction of vessel diameter was observed after three minutes with an average vessel-diameter decrease to 77%. The maximum reduction in vessel diameter was reached eight minutes after sonication with an average vessel diameter decrease to 57% (mean relative diameter reduction of 43%, range 44-61%), ANOVA, p = 0.0002. The vasospasm persisted for all 20 recorded minutes post induction. Vasospasm can be reliably induced by short application of 3 MHz-ultrasound to the CAM vessels. This might be a suitable in vivo model for the evaluation of drug effects on vasospasm in an experimental setting as intermediary in the transition process from in vitro to in vivo assessment using animal models.
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Membrana Corioalantoide , Vasoespasmo Intracraniano , Animais , Galinhas , Membrana Corioalantoide/irrigação sanguínea , Reprodutibilidade dos Testes , UltrassonografiaRESUMO
Background: Delirium and dementia are prominent psychiatric diseases in old age and connected with poor outcomes for people affected. Nevertheless, there is a lack of knowledge concerning the long-term prognosis of patients with dementia and delirium. This study analyzes mortality, readmission rates and discharge destinations of patients with dementia or delirium superimposed on dementia (DSD) within 3 years after discharge from hospital. Methods: A cross-sectional, monocentric cohort study was conducted at the department of geriatric psychiatry of the LVR hospital cologne, using structured telephone interviews and analyses from the clinical information system. All patients with dementia and DSD, admitted between December 2014 and November 2015, were screened for eligibility. Results: In total, 113 patients were included, 49 patients with dementia (M 80 years, female 49%) and 64 with DSD (M 82 years, female 47%). Three years after discharge, 66 patients (58%) had died (95% CI 91.9-112.5; p = 0.53). Within the first 3 months, 9 patients (14%) with DSD deceased, but no patient from the dementia group (95% CI 11.3-12.7; p = 0.01). Out of all patients, 17 patients were readmitted and nursing homes were the predominant discharge destination (55%). Conclusions: This analysis revealed a high post-discharge mortality rate of patients with dementia and DSD. For patients with DSD, a close clinical monitoring, mainly within the first 3 months after discharge, should challenge the significantly increased acute-mortality. These findings should set the pattern for a comprehensive analysis of long-term effects of dementia and DSD. More studies are required for better understanding and comparability in this field of research and healthcare.
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The contribution of the release from sediments to the overall river Trave budget was evaluated with respect to 16 metal(loid)s, three non-metals and the ions PO43- and NH4+. To consider undisturbed conditions and sediment resuspension in-situ dialyses-based and ex-situ suction-based pore water sampling was complemented by sequential extraction and suspension reactor experiments. In the investigated sediments, representative for the study area, metal(loid) partitioning between the different geochemical fractions was very similar despite some higher contaminated spots. Pore water investigations emphasis that profiling and peeper based analyses are comparable and deliver an indication that sediment dwelling organisms are exposed to elevated metal(loid) concentrations. However, higher toxicity of the contaminated sediments compared to the sediment treated as background reference was not revealed. During resuspension only few metal(loid)s exceeded specified guideline values. The maximum amounts released, were only between 10-5 and 10-1% of the average daily load of the river Trave per ton of suspended sediment. Overall the "most pristine sediments" and not the potentially hazardous materials in the study area are found to be from highest concern. The results support requests to better include fractionation and speciation demands in legal assessments of sediments.
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Sleep is a conserved behavioral state. Invertebrates typically show quiet sleep, whereas in mammals, sleep consists of periods of nonrapid-eye-movement sleep (NREMS) and REM sleep (REMS). We previously found that the transcription factor AP-2 promotes sleep in Caenorhabditiselegans and Drosophila In mammals, several paralogous AP-2 transcription factors exist. Sleep-controlling genes are often conserved. However, little is known about how sleep genes evolved from controlling simpler types of sleep to govern complex mammalian sleep. Here, we studied the roles of Tfap2a and Tfap2b in sleep control in mice. Consistent with our results from C. elegans and Drosophila, the AP-2 transcription factors Tfap2a and Tfap2b also control sleep in mice. Surprisingly, however, the two AP-2 paralogs play contrary roles in sleep control. Tfap2a reduction of function causes stronger delta and theta power in both baseline and homeostasis analysis, thus indicating increased sleep quality, but did not affect sleep quantity. By contrast, Tfap2b reduction of function decreased NREM sleep time specifically during the dark phase, reduced NREMS and REMS power, and caused a weaker response to sleep deprivation. Consistent with the observed signatures of decreased sleep quality, stress resistance and memory were impaired in Tfap2b mutant animals. Also, the circadian period was slightly shortened. Taken together, AP-2 transcription factors control sleep behavior also in mice, but the role of the AP-2 genes functionally diversified to allow for a bidirectional control of sleep quality. Divergence of AP-2 transcription factors might perhaps have supported the evolution of more complex types of sleep.
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Privação do Sono/genética , Fases do Sono , Fator de Transcrição AP-2/metabolismo , Animais , Ritmo Circadiano , Ritmo Delta , Memória , Camundongos , Privação do Sono/fisiopatologia , Ritmo Teta , Fator de Transcrição AP-2/genéticaRESUMO
The impact of mechanical disturbance and oxygen induced acidification on the concentration and size fractionation of the 12 metal(loid)s As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sb, Tl, V and the polyatomic nonmetals C, P and S in the pore water was studied. Using the meso profiling and sampling system (messy) 12 pore water depth profiles were sampled from two incubation experiments undertaken in parallel, which were both mechanically disturbed in the lab and subsequently exposed to a different air supply. In parallel to the low invasive, automated sampling process the redox potential, the pH value and the O2 concentration were detected. Simultaneous quantification of all analytes by inductively coupled plasma-triple quad-mass spectrometry in the two different size classes dissolved (<0.45⯵m) and colloidal (0.45-16⯵m) showed: i) the predominant influence of the pH on the mobility of metals; ii) the mobility of metalloids was strongly impacted by the mechanical disturbance; and iii) the colloidal release is less important except for Fe, P, and Ni.
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In an exemplary incubation study with an anaerobic sediment sampled at an oxbow of the river Lahn in Germany (50°18'56.87â³N; 7°37'41.25â³E) and contaminated by former mining activity, a novel meso profiling and sampling system (messy) is presented. Messy enables a low invasive, automated sampling of pore water profiles across the sediment water interface (SWI), down to â¼20 cm depth with a spacial resolution of 1 cm. In parallel to the pore water sampling it measures physicochemical sediment parameters such as redox potential and pH value. In an incubation experiment of 151 days the ability of the setup was proven to address several different aspects relevant for fresh water and marine sediment studies: (i) The influence of mechanical disturbance and oxygen induced acidification on the mobility of 13 metals and metalloids (Cd, Co, Cu, Fe, Mn, Mo, Ni, Sb, U, V, Zn) was quantified based on 11 profiles. The analytes were quantified by inductively coupled plasma-mass spectrometry. Three groups of elements were identified with respect to the release into the pore water and the overlying water under different experimental conditions. (ii) The capability to investigate the impacts of changing physicochemical sediment properties on arsenic and antimony (III/V) speciation is shown. (iii) An approach to obtain information on size fractionation effects and to address the colloidal pore water fractions (0.45 µm-16 µm) was successfully conducted for the elements Ag, As, Cu, Fe and Mn.