Visual quality of life in NMOSD and MOGAD: profiles, dynamics and associations with ageing and vision.

Objective: In this multicentric study, we were interested in the vision-related quality of life and its association with visual impairment in neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in comparison to multiple sclerosis (MS) and healthy controls.

Methods: We analysed extracted data from the German NEMOS registry including National Eye Institute Visual Function Questionnaire (NEI-VFQ) scores, high and low contrast visual acuity (HCVA, LCVA), visually evoked potentials (VEP) and the scores for the expanded disability status scale (EDSS) and other neurological tests which assessed their disease-related impairment. The mean follow-up time of our patients was 1.

Target trial emulation to evaluate the effect of immune-related adverse events on outcomes in metastatic urothelial cancer.

Background: Immune checkpoint inhibitors (ICIs) are an important therapeutic pillar in metastatic urothelial carcinoma (mUC). The occurrence of immune-related adverse events (irAEs) appears to be associated with improved outcomes in observational studies. However, these associations are likely affected by immortal time bias and do not represent causal effects.

Is Whole-Brain Radiotherapy for Brain Metastases an Overestimated Therapy? A Retrospective Study of Real-World Data Using Landmark Analyses.

Background: The role of whole-brain radiotherapy for patients with brain metastases is changing as immunotherapy and molecularly targeted therapies advance. However, whole-brain radiotherapy continues to be part of the multimodal concept.

Methods: This retrospective study included 285 patients who received whole-brain radiotherapy for brain metastases, using a median dose of 30 Gy.

OXTR-mediated signaling in astrocytes contributes to anxiolysis.

Astrocytes are an indispensable part of signal processing within the mammalian brain. Thus, the mode of action of a neuropeptide such as oxytocin (OXT) can only be fully understood considering this integral part of the CNS. Here, we show that OXT regulates astrocytic gene expression, intracellular signaling and specific proteins both in vitro and in vivo.

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.

Elucidating the molecular mechanisms of CCR5-containing extracellular vesicles in vitro and in a rat model of experimental Rheumatoid arthritis.

Extracellular vesicles from Rheumatoid arthritis (RA) derived synovial fibroblasts (EVs) have been implicated in the pathogenesis of RA, acting as mediators of cell-to-cell communication. This study aimed to elucidate the role of the chemokine receptor CCR5 and EVs positive for CCR5 (EVs) in RA, focusing on their impact on cartilage destruction and bone erosion in a rat model of Adjuvant-induced arthritis (AIA). In vivo experiments were conducted using AIA rats, treated with either EVs, EVs without CCR5 (EVs), or EVs which encapsulated the CCR5 antagonist Maraviroc.

Phenotypic screens identify SCAF1 as critical activator of RNAPII elongation and global transcription.

Transcripts produced by RNA polymerase II (RNAPII) are fundamental for cellular responses to environmental changes. It is therefore no surprise that there exist multiple avenues for the regulation of this process. To explore the regulation mediated by RNAPII-interacting proteins, we used a small interfering RNA (siRNA)-based screen to systematically evaluate their influence on RNA synthesis.

A Defined Diet Combined with Sonicated Inoculum Provides a High Incidence, Moderate Severity Form of Experimental Autoimmune Encephalomyelitis (EAE).

Background: Myelin oligodendrocyte glycoprotein 35-55 (MOG)-peptide induced experimental autoimmune encephalomyelitis (EAE) is a model for inflammation of the brain and spinal cord. However, its severity and incidence vary within and between laboratories. Severe scores can lead to premature termination and are both unnecessary for readouts and detrimental to animal welfare.

Consensus Recommendations for Studies of Outflow Facility and Intraocular Pressure Regulation Using Ex Vivo Perfusion Approaches.

Intraocular pressure (IOP) elevation is the primary risk factor and currently the main treatable factor for progression of glaucomatous optic neuropathy. In addition to direct clinical and living animal in vivo studies, ex vivo perfusion of anterior segments and whole eyes is a key technique for studying conventional outflow function as it is responsible for IOP regulation. We present well-tested experimental details, protocols, considerations, advantages, and limitations of several ex vivo model systems for studying IOP regulation.

Low income, being without employment, and living alone: how they are associated with cognitive functioning-Results from the German national cohort (NAKO).

Aim was to investigate to what extent cognitive functioning differs by three socioeconomic conditions: low income, being without employment, and living alone. A total of N = 158,144 participants of the population-based German National Cohort (NAKO) provided data on socioeconomic conditions and completed cognitive tests. Multivariable confounder-adjusted regression analyses indicated that cognitive functioning was lower in those with low income (b = -0.

Association of blood inflammatory phenotypes and asthma burden in children with moderate-to-severe asthma.

Background: Underlying immunological mechanisms in children with moderate-to-severe asthma are complex and unclear. We aimed to investigate the association between blood inflammatory parameters and asthma burden in children with moderate-to-severe asthma.

Methods: Blood inflammatory parameters (eosinophil and neutrophil counts and inflammatory mediators using multiplex immunoassay technology) were measured in children (6-17 years) with moderate-to-severe asthma from the SysPharmPediA cohort across four European countries.

A Comprehensive Functional Investigation of the Human Translocator Protein 18 kDa (TSPO) in a Novel Human Neuronal Cell Knockout Model.

The translocator protein 18 kDa (TSPO) is a multifunctional outer mitochondrial membrane protein associated with various aspects of mitochondrial physiology and multiple roles in health and disease. Here, we aimed to analyse the role of TSPO in the regulation of mitochondrial and cellular functions in a human neuronal cell model. We used the CRISPR/Cas9 technology and generated TSPO knockout (KO) and control (CTRL) variants of human-induced pluripotent stem cells (hiPSCs).

Neutrophils in the Spotlight-An Analysis of Neutrophil Function and Phenotype in ARDS.

Acute respiratory distress syndrome (ARDS) is a complex disease pattern in which pathogenesis polymorphonuclear neutrophil granulocytes (PMN) play a key role. In previous experiments, we could show that interaction with collagen III (an important component of pulmonary tissue) is a possible trigger of neutrophil reactive oxygen species (ROS) production. To investigate possible correlations, further elucidate ARDS pathophysiology, and maybe find pharmacological targets, we evaluated PMNs from blood (circulating PMNs: cPMNs) and tracheal secretion (tPMNs) from patients with and without ARDS with regard to function and phenotype.

Kinetic cooling in mid-infrared methane photoacoustic spectroscopy: A quantitative analysis via digital twin verification.

This study presents a detailed quantitative analysis of kinetic cooling in methane photoacoustic spectroscopy, leveraging the capabilities of a digital twin model. Using a quantum cascade laser tuned to 1210.01 cm⁻¹, we investigated the effects of varying nitrogen-oxygen matrix compositions on the photoacoustic signals of 15 ppmV methane.

Children with MOG-IgG positive bilateral optic neuritis misdiagnosed as fulminant idiopathic intracranial hypertension.

Background: Fulminant idiopathic intracranial hypertension (IIH) is characterized by headache, rapid decrease of vision and elevated CSF-opening pressure.

Objective: To delineate a subgroup of MOGAD mimicking fulminant IIH.

Methods: In this case series children with MOGAD with vision loss, optic disc swelling and elevated CSF opening pressure, initially diagnosed with fulminant IIH, were included.

SLAM-seq reveals independent contributions of RNA processing and stability to gene expression in African trypanosomes.

Gene expression is a multi-step process that converts DNA-encoded information into proteins, involving RNA transcription, maturation, degradation, and translation. While transcriptional control is a major regulator of protein levels, the role of post-transcriptional processes such as RNA processing and degradation is less well understood due to the challenge of measuring their contributions individually. To address this challenge, we investigated the control of gene expression in Trypanosoma brucei, a unicellular parasite assumed to lack transcriptional control.

'You grow with the allergy': a grounded theory study of families' experiences with food allergy risk or diagnosis in early childhood.

Objective: Childhood food allergy is increasing in western societies. Preventing and managing food allergies is therefore essential for both parents and children. Given the limited previous research on parents' experiences of food allergy prevention in early childhood, this study aimed to develop a grounded theory to understand the experiences and interactions of families whose children are at risk of, or have been diagnosed with, food allergy.

Optical Control of TRPM8 Channels with Photoswitchable Menthol.

Transient receptor potential melastatin 8 (TRPM8) channels are well known as sensors for cold temperatures and cooling agents such as menthol and icilin and these channels are tightly regulated by the membrane lipid phosphoinositol-4,5-bisphosphate (PIP). Since TRPM8 channels emerged as promising drug targets for treating pain, itching, obesity, cancer, dry eye disease, and inflammation, we aimed at developing a high-precision TRPM8 channel activator, to achieve spatiotemporal control of TRPM8 activity with light. In this study, we designed, synthesized and characterized the first photoswitchable TRPM8 activator azo-menthol (AzoM).