Different Time Courses of Mono- and Bi-Liganded Bursts of Channel Openings of Adult nAChR Molecules Formed by the Reactions of Transmembrane Regions.

We recorded transmembrane currents through single nicotinic acetylcholine receptors (nAChRs) in cell-attached patches at high temporal resolutions from cultured and transiently transfected HEK 293 cells. Receptor activation was elicited by acetylcholine (ACh) or epibatidine (Ebd) at concentrations ranging from 0.01 to 100 µM, binding to one (R or R) or both extracellular ligand binding sites (R).

The Survey of Neonates in Pomerania: Design, Recruitment and Follow-Up of the Second Cohort, 2013-2017.

Background: The Survey of Neonates in Pomerania (SNiP) is a birth cohort study conducted in Western Pomerania, Germany. SNiP-I recruited participants at birth between the years 2002 and 2008 (5801 inclusions). Since SNiP-I, population sociodemographic characteristics and the prevalence of early exposures, including overweight and gestational diabetes (GDM), have changed.

Management of hereditary angioedema attacks by patients on long-term prophylaxis versus on-demand therapy only.

Despite the use of long-term prophylaxis (LTP) for hereditary angioedema (HAE), the risk of having an attack remains and patients with HAE and on LTP may still experience attacks that can be life threatening. However, the behavioral patterns and perspectives surrounding HAE attack management by patients on LTP are not fully understood. This survey aimed to better understand and compare the behavioral patterns and perspectives, including attitudes and perceptions associated with on-demand treatment among patients on LTP versus those using on-demand therapy only.

No detrimental effect on the hand microbiome of health care staff by frequent alcohol-based antisepsis.

Background: The importance of ethanol-based hand rubs (EBHRs) to prevent health care-associated infections is undisputed. However, there is a lack of meaningful data regarding the influence of EBHRs on skin microbiome.

Methods: Four nurses in a neonatal intensive care unit were included.

Cardiac arrhythmias during and after thoracic irradiation for malignancies.

Background: Cardiac arrhythmia has been reported as a significant complication of thoracic radiotherapy. Both bradyarrhythmias and tachyarrhythmias have been reported, highlighting the arrhythmia-modulating potential of radiation in certain oncologic therapies. This study aimed to analyse the arrhythmic burden in patients with cardiac implantable electrical devices (CIEDs) undergoing thoracic irradiation, examining both immediate effects of radiotherapy and long-term sequelae post-therapy.

Discovery of BAY 2413555, First Selective Positive Allosteric Modulator of the M2 Receptor to Restore Cardiac Autonomic Balance.

Autonomic disbalance, i.e., sympathetic overactivation and parasympathetic withdrawal, is a causal driver of disease progression in heart failure.

Structural and functional mechanisms of anti-NMDAR autoimmune encephalitis.

Autoantibodies against neuronal membrane proteins can manifest in autoimmune encephalitis, inducing seizures, cognitive dysfunction and psychosis. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most dominant autoimmune encephalitis; however, insights into how autoantibodies recognize and alter receptor functions remain limited. Here we determined structures of human and rat NMDARs bound to three distinct patient-derived antibodies using single-particle electron cryo-microscopy.

Impact of Maternal Pre-Pregnancy Underweight on Cord Blood Metabolome: An Analysis of the Population-Based Survey of Neonates in Pomerania (SNiP).

Intrauterine growth restriction leads to an altered lipid and amino acid profile in the cord blood at the end of pregnancy. Pre-pregnancy underweight is an early risk factor for impaired fetal growth. The aim of this study was to investigate whether a pre-pregnancy body mass index (ppBMI) of <18.

The complexities of decision-making associated with on-demand treatment of hereditary angioedema (HAE) attacks.

Background: Hereditary angioedema (HAE) is characterized by debilitating attacks of tissue swelling in various locations. While guidelines recommend the importance of early on-demand treatment, recent data indicate that many patients delay or do not treat their attacks.

Objective: This survey aimed to investigate patient behavior and evaluate the key factors that drive on-demand treatment decision-making, as reported by those living with HAE.

Increased expression of human endogenous retrovirus K in endomyocardial biopsies from patients with cardiomyopathy - a transcriptomics meta-analysis.

Most studied, investigating transcriptional changes in myocardial biopsies focus on human genes. However, the presence and potential consequence of persistent expression of viral genes within the myocardium is unclear. The aim of the study was to analyze viral gene expression in RNAseq data from endomyocardial biopsies.

CIME4R: Exploring iterative, AI-guided chemical reaction optimization campaigns in their parameter space.

Chemical reaction optimization (RO) is an iterative process that results in large, high-dimensional datasets. Current tools allow for only limited analysis and understanding of parameter spaces, making it hard for scientists to review or follow changes throughout the process. With the recent emergence of using artificial intelligence (AI) models to aid RO, another level of complexity has been added.

Efficacy and safety of BRAF/MEK inhibitors in BRAFV600E-mutated anaplastic thyroid cancer: a systematic review and meta-analysis.

Purpose: Approximately 45% of anaplastic thyroid cancer (ATC) patients harbor a BRAF mutation and are eligible for target therapy (TT) with BRAF and MEK inhibitors (BRAFi/MEKi), nevertheless, few data advocate for this. Hence, we've conducted a systematic review and meta-analysis investigating the effectiveness and safety of BRAFi/MEKi in BRAF ATC patients.

Methods: PubMed, Embase, and the Cochrane Library were systematically searched for BRAFi/MEKi TT in BRAF ATC patients.

Identification of Oxidative-Stress-Reducing Plant Extracts from a Novel Extract Library-Comparative Analysis of Cell-Free and Cell-Based In Vitro Assays to Quantitate Antioxidant Activity.

Numerous underexplored plant species are believed to possess considerable potential in combating oxidative stress and its associated health impacts, emphasizing the need for a comprehensive methodological screening approach to assess their antioxidant capacity. This study investigated 375 plant extracts, utilizing both cell-free and cellular methods to evaluate their antioxidant properties. Target-based antioxidant capacity was evaluated by the total phenolic content (TPC) and ferric reducing antioxidant power (FRAP) assays.

Steroid Metabolomic Signature in Term and Preterm Infants.

Adrenal function is essential for survival and well-being of preterm babies. In addition to glucocorticoids, it has been hypothesized that C-steroids (DHEA-metabolites) from the fetal zone of the adrenal gland may play a role as endogenous neuroprotective steroids. In 39 term-born (≥37 weeks gestational age), 42 preterm (30-36 weeks) and 51 early preterm (<30 weeks) infants 38 steroid metabolites were quantified by GC-MS in 24-h urinary samples.

Intracellular Delivery of Functional Proteins with DNA-Protein Nanogels-Lipids Complex.

Using functional proteins for therapeutic purposes due to their high selectivity and/or catalytic properties can enable the control of various cellular processes; however, the transport of active proteins inside living cells remains a major challenge. In contrast, intracellular delivery of nucleic acids has become a routine method for a number of applications in gene therapy, genome editing, or immunization. Here we report a functionalizable platform constituting of DNA-protein nanogel carriers cross-linked through streptavidin-biotin or streptactin-biotin interactions and demonstrate its applicability for intracellular delivery of active proteins.

Cardiological parameters predict mortality and cardiotoxicity in oncological patients.

Aims: Oncological patients suspected at risk for cardiotoxicity are recommended to undergo intensified cardiological surveillance. We investigated the value of cardiac biomarkers and patient-related risk factors [age, cardiovascular risk factors (CVRFs), and cardiac function] for the prediction of all-cause mortality (ACM) and the development of cardiotoxicity.

Methods And Results: Between January 2016 and December 2020, patients with oncological diseases admitted to the Cardio-Oncology Unit at the Heidelberg University Hospital were included.

Human NMDAR autoantibodies disrupt excitatory-inhibitory balance, leading to hippocampal network hypersynchrony.

Anti-NMDA receptor autoantibodies (NMDAR-Abs) in patients with NMDAR encephalitis cause severe disease symptoms resembling psychosis and cause cognitive dysfunction. After passive transfer of patients' cerebrospinal fluid or human monoclonal anti-GluN1-autoantibodies in mice, we find a disrupted excitatory-inhibitory balance resulting from CA1 neuronal hypoexcitability, reduced AMPA receptor (AMPAR) signaling, and faster synaptic inhibition in acute hippocampal slices. Functional alterations are also reflected in widespread remodeling of the hippocampal proteome, including changes in glutamatergic and GABAergic neurotransmission.

Development of a joint set of database parameters for the EU-ROP and Fight Childhood Blindness! ROP Registries.

Background/aims: The incidence of retinopathy of prematurity (ROP) is increasing and treatment options are expanding, often without accompanying safety data. We aimed to define a minimal, patient-centred data set that is feasible to collect in clinical practice and can be used collaboratively to track and compare outcomes of ROP treatment with a view to improving patient outcomes.

Methods: A multinational group of clinicians and a patient representative with expertise in ROP and registry development collaborated to develop a data set that focused on real-world parameters and outcomes that were patient centred, minimal and feasible to collect in routine clinical practice.

Nanoscaled RIM clustering at presynaptic active zones revealed by endogenous tagging.

Chemical synaptic transmission involves neurotransmitter release from presynaptic active zones (AZs). The AZ protein Rab-3-interacting molecule (RIM) is important for normal Ca-triggered release. However, its precise localization within AZs of the glutamatergic neuromuscular junctions of remains elusive.

Association between maternal pre-pregnancy body mass index and offspring's outcomes at 9 to 15 years of age.

Objective: Maternal pre-pregnancy underweight, overweight and obesity might increase the risk for worse short- and long-term outcome in the offspring. There is a need for further study into the relationship between maternal pre-pregnancy body mass index (BMI) and the combined outcome of physical development, state of health and social behavior in children.

Question: Is maternal pre-pregnancy BMI associated with the child outcome in terms of physical development, state of health and social behavior (school and leisure time behavior) at the age of 9 to 15 years?

Methods: In the population-based birth cohort study Survey of Neonates in Pomerania (SNIP) children at the age 9-15 years and their families were re-examined by questionnaire-based follow-up.

Cardiomuscular Biomarkers in the Diagnosis and Prognostication of Immune Checkpoint Inhibitor Myocarditis.

Background: Immune checkpoint inhibitors (ICIs) are approved for multiple cancers but can result in ICI-associated myocarditis, an infrequent but life-threatening condition. Elevations in cardiac biomarkers, specifically troponin-I (cTnI), troponin-T (cTnT), and creatine kinase (CK), are used for diagnosis. However, the association between temporal elevations of these biomarkers with disease trajectory and outcomes has not been established.

Indomethacin Prophylaxis Is Associated with Reduced Risk of Intraventricular Hemorrhage in Extremely Preterm Infants Born in the Context of Amniotic Infection Syndrome.

Background: Amniotic infection syndrome (AIS) with perinatal inflammation may increase the susceptibility to intraventricular hemorrhage (IVH) in preterm infants. Given its anti-inflammatory and ductus arteriosus constricting capacities, we hypothesized that prophylactic administration of indomethacin reduces the incidence, severity, and consequences of IVH in the context of perinatal inflammation.

Methods: We evaluated data of infants born between 2009 and 2020 of 22 + 0-25+6 weeks of gestation from 68 German Neonatal Network centers.

Antenatal Care and Health Behavior of Pregnant Women-An Evaluation of the Survey of Neonates in Pomerania.

Background: The German maternity guidelines require regular medical checkup (MC) during pregnancy as a measure of prevention. Socioeconomic factors such as education, profession, income and origin, but also age and parity may influence the preventive and health behavior of pregnant women. The aim was to investigate the influence of these factors on the participation rate in MC of pregnant women.

Flexible Changes in Attentional Focus and Task Rules Rely on A Shared Set of Frontoparietal Oscillatory Dynamics.

Flexible changes in behavior can involve changes in the processing of external information (i.e., shifts in attention between different stimuli) or internal information (i.