Epigenome-wide association study of objectively measured physical activity in peripheral blood leukocytes.

Background: Few studies have explored the association between DNA methylation and physical activity. The aim of this study was to evaluate the association of objectively measured hours of sedentary behavior (SB) and moderate physical activity (MPA) with DNA methylation. We further aimed to explore the association between SB or MPA related CpG sites and cardiometabolic traits, gene expression, and genetic variation.

Rock strength controls erosion in tectonically dead landscapes.

Interactions among tectonics, climate, and lithology shape the Earth's surface. In regions dominated by tectonic quiescence and climate stability, the role of rock strength related to lithology, and its role in landscape evolution, can be most clearly perceived. We leverage these qualities in a unique field site by integrating topographic data, erosion rates, and a large suite of rock strength measurements to quantify the relationship between bedrock strength and erosion rates along a 200-km section of the southeast coast of Brazil where climatic and tectonic variability are minimal.

Impaired Presynaptic Function Contributes Significantly to the Pathology of Glycine Receptor Autoantibodies.

Background And Objectives: Autoantibodies (aAbs) against glycine receptors (GlyRs) are mainly associated with the rare neurologic diseases stiff person syndrome (SPS) and progressive encephalomyelitis with rigidity and myoclonus (PERM). GlyR aAbs are also found in other neurologic diseases such as epilepsy. The aAbs bind to different GlyR α-subunits and, more rarely, also to the GlyR β-subunit.

Automated electronic health record-based screening for Fabry disease in unexplained left ventricular hypertrophy (FAPREV-HCM).

Background And Aims: Hypertrophic cardiomyopathy (HCM) has various aetiologies, including genetic conditions like Fabry disease (FD), a lysosomal storage disorder. FD prevalence in high-risk HCM populations ranges from 0.3% to 11.

Super-resolution expansion microscopy in plant roots.

Super-resolution methods provide far better spatial resolution than the optical diffraction limit of about half the wavelength of light (∼200-300 nm). Nevertheless, they have yet to attain widespread use in plants, largely due to plants' challenging optical properties. Expansion microscopy improves effective resolution by isotropically increasing the physical distances between sample structures while preserving relative spatial arrangements and clearing the sample.

[Pilon fractures : Treatment principles and surgical therapy strategy].

Pilon fractures typically result from high-energy trauma combined with axial compression. The surrounding soft tissues are often severely compromised, complicating treatment. These fractures are best classified according to the Working Group for Osteosynthesis Issues/Orthopedic Trauma Association (AO/OTA) classification system.

Small fiber pathology in fibromyalgia syndrome.

About 50% of women with fibromyalgia syndrome have reduced skin innervation. This finding is consistent in patient cohorts from different regions of the world. Small fiber function may also be affected, as shown by various studies using different methods, such as quantitative sensory testing or special small fiber neurophysiology such as C-fiber microneurography.

Protein purification with light via a genetically encoded azobenzene side chain.

Affinity chromatography is the method of choice for the rapid purification of proteins from cell extracts or culture supernatants. Here, we present the light-responsive Azo-tag, a short peptide comprising p-(phenylazo)-L-phenylalanine (Pap), whose side chain can be switched from its trans-ground state to the metastable cis-configuration by irradiation with mild UV light. Since only trans-Pap shows strong affinity to α-cyclodextrin (α-CD), a protein exhibiting the Azo-tag selectively binds to an α-CD chromatography matrix under daylight or in the dark but elutes quickly under physiological buffer flow when illuminating the column at 355 nm.

TAM receptors mediate the Fpr2-driven pain resolution and fibrinolysis after nerve injury.

Nerve injury causes neuropathic pain and multilevel nerve barrier disruption. Nerve barriers consist of perineurial, endothelial and myelin barriers. So far, it is unclear whether resealing nerve barriers fosters pain resolution and recovery.

Altered blood and keratinocyte microRNA/transfer RNA fragment profiles related to fibromyalgia syndrome and its severity.

Fibromyalgia syndrome (FMS) is a debilitating widespread chronic pain condition of unclear pathophysiology. We studied small noncoding RNAs as potential classifiers and mediators of FMS. Blood and keratinocyte microRNAs (miRs) and transfer RNA fragments (tRFs) were profiled by small RNA-sequencing within a comprehensively phenotyped female cohort of 53 patients with FMS vs 34 healthy controls (hCOs) and 15 patients with major depression and chronic physical pain (disease controls).

Revival of recombinant IL-2 therapy - approaches from the past until today.

Interleukin-2 (IL-2) was one of the first cytokines discovered and its central role in T cell function soon led to the notion that the cytokine could specifically activate immune cells to combat cancer cells. Recombinant human IL-2 (recIL-2) belonged to the first anti-cancer immunotherapeutics that received marketing authorization and while it mediated anti-tumor effects in some cancer entities, treatment was associated with severe and systemic side effects. RecIL-2 holds an exceptional therapeutic potential, which can either lead to stimulation of the immune system - favorable during cancer treatment - or immunosuppression - used for treatment of inflammatory diseases such as autoimmunity.

Type 2 responses determine skin rash during recombinant interleukin-2 therapy.

The skin is the organ most often affected by adverse drug reactions. Although these cutaneous adverse drug reactions (CADRs) often are mild, they represent a major burden for patients. One of the drugs inducing CADRs is aldesleukin, a recombinant interleukin-2 (recIL-2) originally approved to treat malignant melanoma and metastatic renal cell carcinoma which frequently led to skin rashes when applied in high doses for anti-cancer therapy.

Using interactive platforms to encode, manage and explore immune-related adverse outcome pathways.

This work focuses on the need for modeling and predicting adverse outcomes in immunotoxicology to improve nonclinical assessments of the safety of immunomodulatory therapies. The integrated approach includes, first, the adverse outcome pathway concept established in the toxicology field, and, second, the systems medicine disease map approach for describing molecular mechanisms involved in a particular pathology. The proposed systems immunotoxicology workflow is illustrated with chimeric antigen receptor (CAR) T cell treatment as a use case.

Evaluating the reproducibility of a deep learning algorithm for the prediction of retinal age.

Recently, a deep learning algorithm (DLA) has been developed to predict the chronological age from retinal images. The Retinal Age Gap (RAG), a deviation between predicted age from retinal images (Retinal Age, RA) and chronological age, correlates with mortality and age-related diseases. This study evaluated the reliability and accuracy of RA predictions and analyzed various factors that may influence them.

Prenatal to Adulthood: The Responsibility of the Speech-Language Pathologist on the Comprehensive Cleft Palate and Craniofacial Team.

Purpose: Comprehensive cleft care is an important component when caring for a child with cleft palate with or without cleft lip (CP ± L). Speech-language pathologists (SLPs) serve different capacities on comprehensive cleft palate and craniofacial teams.

Method: This tutorial highlights the role of the SLP on the cleft palate and craniofacial team from the prenatal consultation to adulthood.

Antibody selection and automated quantification of TRPV1 immunofluorescence on human skin.

Assessing localization of the transient receptor potential vanilloid-1 (TRPV1) in skin nerve fibers is crucial for understanding its role in peripheral neuropathy and pain. However, information on the specificity and sensitivity of TRPV1 antibodies used for immunofluorescence (IF) on human skin is currently lacking. To find a reliable TRPV1 antibody and IF protocol, we explored antibody candidates from different manufacturers, used rat DRG sections and human skin samples for screening and human TRPV1-expressing HEK293 cells for further validation.

Position Paper of the German Society for Interventional Radiology and Minimally Invasive Therapy (DeGIR) and the German Roentgen Society (DRG) on Structural and Professional Requirements in Interventional Oncology.

Interventional oncology (IO) employs various techniques to enable minimally invasive, image-guided treatment of tumor diseases with both curative and palliative goals. Additionally, it significantly contributes to managing tumor-related and perioperative complications, offering diverse supportive procedures for patients at all stages of their diseases. The execution of IO procedures places unique demands on the equipment, personnel, and structural organization of radiological clinics, necessitating specific expertise from interventional radiologists.

Impact of the Covid19 pandemic on health-related quality of life in patients with Fabry disease - implications for future care of patients with rare diseases.

Background: The worldwide Covid19 pandemic caused by the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represented a unique challenge for patients and healthcare professionals. Patients with chronic rare diseases had to face novel burdens, like the inability to perform regular on-site visits or even difficulties in the supply of medication. Patients with Fabry disease (FD) are affected by a variety of organ manifestations leading to physical but also psychological burden and limitations, which are usually presented in low health-related quality of life (HR-QoL).

A New Retest-Stable Tortuosity Metric for Retinal Vessel Analyses.

Purpose: Existing retinal vessel tortuosity metrics lack standardization and retest reliability, hindering their clinical utility. Our study addresses this gap by introducing a novel metric, coined as the "vascular curvature index" (VCI), to enhance accuracy and consistency in biomarkers associated with medical conditions. We assess VCI's performance in terms of retest reliability in healthy subjects to transform early detection and monitoring approaches for various diseases.

Case report: target antigen and subclass switch in a patient with autoimmune nodopathy.

Introduction: Autoimmune nodopathy (AN) is a new entity in the field of peripheral neuropathies and is defined by the presence of auto-antibodies against structures of the node of Ranvier combined with specific clinico-pathophysiological features and therapy response in affected patients. The target-specific antibodies do not only serve as diagnostic biomarkers but also for treatment evaluation during follow-up.

Case Report: We report a 66-year-old female patient with various autoimmune diseases, including a history of membranous glomerulonephritis which presented with acute-onset, sensorimotor tetraparesis, cranial nerve involvement, and mild respiratory insufficiency.

Spinal neuron diversity scales exponentially with swim-to-limb transformation during frog metamorphosis.

Vertebrates exhibit a wide range of motor behaviors, ranging from swimming to complex limb-based movements. Here we take advantage of frog metamorphosis, which captures a swim-to-limb-based movement transformation during the development of a single organism, to explore changes in the underlying spinal circuits. We find that the tadpole spinal cord contains small and largely homogeneous populations of motor neurons (MNs) and V1 interneurons (V1s) at early escape swimming stages.