Mutation-induced LZTR1 polymerization provokes cardiac pathology in recessive Noonan syndrome.

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 LZTR1 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 LZTR1-specific disease mechanism provoking cardiac hypertrophy.

Multi-element analysis of unfiltered samples in river water monitoring-digestion and single-run analyses of 67 elements.

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.

Efficiency of five samplers to trap suspended particulate matter and microplastic particles of different sizes.

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.

Physical activity monitoring-based interventions in geriatric patients: a scoping review on intervention components and clinical applicability.

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.

Quantification of 68 elements in river water monitoring samples in single-run measurements.

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).

Dance-Specific Activity in People Living With Dementia: A Conceptual Framework and Systematic Review of Its Effects on Neuropsychiatric Symptoms.

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.

Metabolic Tumor Imaging with Rapidly Signal-Enhanced 1- C-Pyruvate-d.

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- C-pyruvate-d , 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- 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.

Post-discharge Mortality in Patients With Delirium and Dementia: A 3-Year Follow Up Study.

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.

In Vivo Vasospasm Induction by Ultrasound Application in the Chicken Chorioallantoic Membrane Model.

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.

Ultrasound-Induced Release of Nimodipine from Drug-Loaded Block Copolymer Micelles: In Vivo Analysis.

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.

Functional Divergence of Mammalian TFAP2a and TFAP2b Transcription Factors for Bidirectional Sleep Control.

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 and In mammals, several paralogous AP-2 transcription factors exist.

Sediment water (interface) mobility of metal(loid)s and nutrients under undisturbed conditions and during resuspension.

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 PO and NH. 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.

Impact of mechanical disturbance and acidification on the metal(loid) and C, P, S mobility at the sediment water interface examined using a fractionation meso profiling ICP-QQQ-MS approach.

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 O concentration were detected.

Metal(loid) speciation and size fractionation in sediment pore water depth profiles examined with a new meso profiling system.

In an exemplary incubation study with an anaerobic sediment sampled at an oxbow of the river Lahn in Germany (50°18'56.87″N; 7°37'41.25″E) and contaminated by former mining activity, a novel meso profiling and sampling system (messy) is presented.

Experimental and computational X-ray emission spectroscopy as a direct probe of protonation states in oxo-bridged Mn(IV) dimers relevant to redox-active metalloproteins.

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 Kβ 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.

Electronic structural changes of Mn in the oxygen-evolving complex of photosystem II during the catalytic cycle.

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.