Manual handling and back pain among health care professionals in neurological inpatient and outpatient settings: a mixed methods study.

Background: The number of patients with neurological disorders and severe disability is increasing globally. These patients often need help with positioning and the amount of support varies with their level of impairment. High rates of work-related musculoskeletal disorders are observed among healthcare professionals (HCP) with patient contact due to injuries during manual handling.

A stratified treatment algorithm in psychiatry: a program on stratified pharmacogenomics in severe mental illness (Psych-STRATA): concept, objectives and methodologies of a multidisciplinary project funded by Horizon Europe.

Schizophrenia (SCZ), bipolar (BD) and major depression disorder (MDD) are severe psychiatric disorders that are challenging to treat, often leading to treatment resistance (TR). It is crucial to develop effective methods to identify and treat patients at risk of TR at an early stage in a personalized manner, considering their biological basis, their clinical and psychosocial characteristics. Effective translation of theoretical knowledge into clinical practice is essential for achieving this goal.

Analysis of Light-Controlled Artificial Cell-Cell Adhesions.

The precise spatial and temporal regulation of cell-cell adhesions is crucial for understanding the underlying biological processes and for assembling multicellular structures in tissue engineering. Traditional approaches have relied on chemical membrane functionalization and regulated gene expression of native cell adhesion molecules (CAMs), but these methods lack the necessary control and can be detrimental to cells. In contrast, engineered photoswitchable cell-cell adhesions offer a reversible and dynamic regulation at a single-cell resolution.

TKK130 is a 3-Hydroxy-Propanamidine (HPA) with Potent Antimalarial Activity and a High Barrier to Resistance.

Malaria continues to pose a significant burden on populations in endemic areas and requires innovative treatment options. Here, we report the synthesis and preclinical evaluation of the novel 3-hydroxypropanamidine (HPA) , which shows excellent antiplasmodial activity against drug-sensitive and -resistant strains. Moreover, in various human cell lines, the compound shows no cytotoxicity and excellent parasite selectivity.

Ten-Year Outcomes and Predictors of Mortality Following Catheter Ablation of Ventricular Tachycardia.

Background: Catheter ablation is the primary treatment option for idiopathic ventricular tachycardia (VT). It plays a key role in acute therapy of electrical storm, treatment of VTs in patients with structural heart disease (SHD), and can reduce VT burden. Here we report on 10-year clinical outcomes following VT ablation from patients enrolled in the prospective German Ablation Registry.

Vagus nerve stimulation and gut microbiota interactions: A novel therapeutic avenue for neuropsychiatric disorders.

The rising prevalence of treatment-resistant neuropsychiatric disorders underscores the need for innovative and effective treatment strategies. The gut microbiota (GM) plays a pivotal role in the progression of these diseases, influencing the brain and mental health through the gut-brain axis (GBA). The vagus nerve plays a significant role in the GBA, making it a key area of focus for potential novel therapeutic interventions.

Adaptive metal ion transport and metalloregulation-driven differentiation in pluripotent synthetic cells.

Pluripotent cells can yield different cell types determined by the specific sequence of differentiation signals that they encounter as the cell activates or deactivates functions and retains memory of previous inputs. Here, we achieved pluripotency in synthetic cells by incorporating three dormant apo-metalloenzymes such that they could differentiate towards distinct fates, depending on the sequence of specific metal ion transport with ionophores. In the first differentiation step, we selectively transported one of three extracellular metal ion cofactors into pluripotent giant unilamellar vesicles (GUVs), which resulted in elevation of intracellular pH, hydrogen peroxide production or GUV lysis.

Corrigendum to [Int J Cardiol Congenit Heart Dis 9 September 2022 100394].

[This corrects the article DOI: 10.1016/j.ijcchd.

Hyperreflective material evolution patterns during long term anti-VEGF therapy in neovascular age-related macular degeneration.

This retrospective, real-life cohort was analyzed to detect the frequency of different HRM evolution patterns and their correlation with MNV types, morphological and functional changes in exudative nAMD under long-term anti-VEGF therapy. We evaluated optical coherence tomography (OCT) volume scans in 143 eyes of 94 nAMD patients (start of anti-VEGF therapy 2009-2018, therapy until the last visit) and recorded the VA at all visits. HRM evolution patterns were differentiated: pattern 1 = no HRM, pattern 2 = subretinal HRM resolved during follow-up, pattern 3 = persistent subretinal HRM with new HRM-boundary remodeling [BR], pattern 4 = persistent subretinal HRM without HRM-BR.

Correlation Between Progression-Free and Overall Survival in Patients with Hodgkin Lymphoma: A Comprehensive Analysis of Individual Patient Data from Randomized GHSG Trials.

Background: We aimed to evaluate the correlation of progression-free (PFS) and overall survival (OS) after first-line treatment of classical Hodgkin lymphoma (HL) and the potential of PFS to serve as a surrogate parameter for OS.

Patients And Methods: We analyzed individual patient data obtained during and after treatment with polychemotherapy within nine randomized phase III trials (GHSG HD7-HD15) between 01/93 - 08/18. Effects of 16 experimental treatments on PFS and OS on trial level were evaluated by estimation of the treatment effects with Cox proportional hazards (PH) regression and a linear weighted least squares regression.

Decoupling the Effects of Interface Chemical Degradation and Mechanical Cracking in Solid-State Batteries with Silicon Electrode.

Silicon is a promising negative electrode material for solid-state batteries (SSBs) due to its high specific capacity and ability to prevent lithium dendrite formation. However, SSBs with silicon electrodes currently suffer from poor cycling stability, despite chemical engineering efforts. This study investigates the cycling failure mechanism of composite Si/LiPSCl electrodes by decoupling the effects of interface chemical degradation and mechanical cracking.

Comparison of fludarabine/melphalan (FM140) with fludarabine/melphalan/BCNU (FBM110) in patients with relapsed/refractory AML undergoing allogeneic hematopoietic cell transplantation - a registry study on behalf of the EBMT Acute Leukemia Working Party.

The treatment of relapsed/refractory acute myeloid leukemia (AML) is associated with a dismal prognosis. The allogeneic hematopoietic cell transplantation (allo-HCT) is frequently performed as salvage therapy. Reduced intensity conditioning protocols have been developed with the aim of reducing the leukemia burden without increasing their toxicity.

A family of NADPH/NADP biosensors reveals in vivo dynamics of central redox metabolism across eukaryotes.

The NADPH/NADP redox couple is central to metabolism and redox signalling. NADP redox state is differentially regulated by distinct enzymatic machineries at the subcellular compartment level. Nonetheless, a detailed understanding of subcellular NADP redox dynamics is limited by the availability of appropriate tools.

Cytosolic S100A8/A9 promotes Ca supply at LFA-1 adhesion clusters during neutrophil recruitment.

S100A8/A9 is an endogenous alarmin secreted by myeloid cells during many acute and chronic inflammatory disorders. Despite increasing evidence of the proinflammatory effects of extracellular S100A8/A9, little is known about its intracellular function. Here, we show that cytosolic S100A8/A9 is indispensable for neutrophil post-arrest modifications during outside-in signaling under flow conditions in vitro and neutrophil recruitment in vivo, independent of its extracellular functions.

The serum biomarkers NSE and S100B predict intracranial complications and in-hospital survival in patients undergoing veno-venous ECMO.

Neurological complications in patients undergoing veno-venous extracorporeal membrane oxygenation (V-V ECMO) are challenging, with new intracranial pathologies posing a grave risk. We aimed to evaluate the utility of neuron-specific enolase (NSE) and S100B biomarkers for predicting outcomes in new-onset intracranial pathology during V-V ECMO. A retrospective analysis spanning 2013-2021 at a German university hospital was conducted.

Deep proteomics and network pharmacology reveal sex- and age-shared neuropathic pain signatures in mouse dorsal root ganglia.

Our understanding of how sex and age influence chronic pain at the molecular level is still limited with wide-reaching consequences for adolescent patients. Here, we leveraged deep proteome profiling of mouse dorsal root ganglia (DRG) from adolescent (4-week-old) and adult (12-week-old) male and female mice to investigate the establishment of neuropathic pain in the spared nerve injury (SNI)-model in parallel. We quantified over 12,000 proteins, including notable ion channels involved in pain, highlighting the sensitivity of our approach.

Choroid plexus morphology in schizophrenia and early-stage psychosis: A cross-sectional study.

Background: The choroid plexus is an important structure within the ventricular system. Schizophrenia has been associated with morphological changes to the choroid plexus but the presence and extent of alterations at different illness stages is unclear.

Methods: We examined choroid plexus volumes in participants at clinical high-risk for psychosis (N = 110), participants with first-episode psychosis (N = 37), participants with schizophrenia (N = 28), clinical (N = 38) and non-clinical controls (N = 75).

Nanocarriers for intracellular delivery of molecular payloads triggered by visible light.

Stimuli-responsive nanocontainers have emerged as promising vehicles to deliver molecular payloads into the cytosol of cells in a spatially, temporally and dosage-controlled manner. These nanocontainers respond to a specific type of stimulus such as a change in redox status, enzymatic activity, pH, heat, light, and others. In this work, we introduce photoresponsive nanocontainers based on the self-assembly of vesicles with surface-confined cyclodextrin-adamantane host-guest chemistry.

A pair of two atrial myxomas mimic thrombus in left atrial appendage and cause ischemic stroke in a young adult: a case report.

Background: Stroke is one of the leading causes of mortality and disability and can be rarely caused by cardiac myxoma.

Case Summary: Here, we report about a 56-year-old man who suffered from a stroke presented with acute dysarthria and left hemiparesis. Magnetic resonance imaging (MRI) of the brain revealed an acute stroke.

Abatacept Induces Long-Term Reconstitution of the B-Cell Niche in a Patient With CTLA-4 Haploinsufficiency: A Case Report.

Objectives: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) haploinsufficiency is a rare genetic condition characterized by development of immune cytopenia, hypogammaglobulinemia, and/or lymphoproliferative disorder, as well as multiple autoimmunity. Treatment with abatacept was shown to alleviate autoimmune conditions, yet its long-lasting impact on bone marrow function remains undetermined.

Methods: We here present the case of a now 39-year-old woman with CTLA-4 haploinsufficiency with predominant CNS affection, yet multiorgan autoimmunity and lymphopenia.

Ocean-Wide Conservation Genomics of Blue Whales Suggest New Northern Hemisphere Subspecies.

The blue whale is an endangered and globally distributed species of baleen whale with multiple described subspecies, including the morphologically and genetically distinct pygmy blue whale. North Atlantic and North Pacific populations, however, are currently regarded as a single subspecies despite being separated by continental land masses and acoustic call differences. To determine the degree of isolation among the Northern Hemisphere populations, 14 North Pacific and 6 Western Australian blue whale nuclear and mitochondrial genomes were sequenced and analysed together with 11 publicly available North Atlantic blue whale genomes.

Maintenance therapy with trofosfamide, idarubicin and etoposide in patients with rhabdomyosarcoma and other high-risk soft tissue sarcomas (CWS-2007-HR): a multicentre, open-label, randomised controlled phase 3 trial.

Background: Rhabdomyosarcoma and other soft tissue sarcomas (STS) with high-risk features are still associated with an unsatisfactory outcome. We evaluated the efficacy of oral maintenance therapy added at the end of standard therapy in patients with high-risk rhabdomyosarcoma and STS.

Methods: CWS-2007-HR was a multicentre, open-label, randomised controlled, phase 3 trial done at 87 centers in 5 countries.

The Thermo-Oxidative Degradation of Polyurethane Open-Cell Soft Foam Investigated Through Gas Chromatography and Mass Spectrometry of Volatile Organic Compounds.

Polyurethane (PUR) soft foams release malodorous and potentially toxic compounds when exposed to oxidative conditions. Current chamber test methods cannot distinguish between pre-existing volatiles and those formed during oxidation, nor can they assess the formation rates of oxidation products. We subjected PUR soft foam to oxidative treatment in a continuous air flow at 120 °C.

Development and validation of a quantification method for direct oral anticoagulants from capillary blood using volumetric absorptive microsampling and online SPE-LC-MS.

The number of prescriptions for new direct oral anticoagulants (DOACs) apixaban, edoxaban, rivaroxaban and dabigatran has increased exponentially in recent years, increasingly replacing the old gold standard, vitamin-K-antagonists. Due to their wide therapeutic range, therapeutic drug monitoring (TDM) is not required, although it has been proven that this could significantly reduce side effects. In order to develop a cost-efficient and simple method for the simultaneous detection of the DOACs and phenprocoumon, a new technology for sample preparation from capillary blood in the ambulant sector named VAMS® was integrated and an LC-MS detector with on-line solid phase extraction (SPE) applying a Turboflow HTLC Cyclone 1.

The distinctive mechanical and structural signatures of residual force enhancement in myofibers.

In muscle, titin proteins connect myofilaments together and are thought to be critical for contraction, especially during residual force enhancement (RFE) when steady-state force is elevated after an active stretch. We investigated titin's function during contraction using small-angle X-ray diffraction to track structural changes before and after 50% titin cleavage and in the RFE-deficient, titin mutant. We report that the RFE state is structurally distinct from pure isometric contractions, with increased thick filament strain and decreased lattice spacing, most likely caused by elevated titin-based forces.