Side-effect expectations are associated with disability, physical fitness, and somatic symptoms 3 months after post-COVID neurological inpatient rehabilitation.

Introduction: The COVID-19 pandemic, caused by SARS-CoV-2, has led to long-term health issues known as post-COVID-19 condition, including fatigue and cognitive disruptions. Despite its recognition as a public health concern, the efficacy of therapeutic interventions, especially in neurological rehabilitation, remains unclear. This study examines how treatment expectations are associated with psychological and physical outcomes in post-COVID-19 condition neurological rehabilitation.

Immortalised murine R349P desmin knock-in myotubes exhibit a reduced proton leak and decreased ADP/ATP translocase levels in purified mitochondria.

Desmin gene mutations cause myopathies and cardiomyopathies. Our previously characterised R349P desminopathy mice, which carry the ortholog of the common human desmin mutation R350P, showed marked alterations in mitochondrial morphology and function in muscle tissue. By isolating skeletal muscle myoblasts from offspring of R349P desminopathy and p53 knock-out mice, we established an immortalised cellular disease model.

Clinorotation inhibits myotube formation by fluid motion, not by simulated microgravity.

To study processes related to weightlessness in ground-based cell biological research, a theoretically assumed microgravity environment is typically simulated using a clinostat - a small laboratory device that rotates cell culture vessels with the aim of averaging out the vector of gravitational forces. Here, we report that the rotational movement during fast clinorotation induces complex fluid motions in the cell culture vessel, which can trigger unintended cellular responses. Specifically, we demonstrate that suppression of myotube formation by 2D-clinorotation at 60 rpm is not an effect of the assumed microgravity but instead is a consequence of fluid motion.

Effects of long-term immobilisation on endomysium of the soleus muscle in humans.

New Findings: What is the central question of this study? While muscle fibre atrophy in response to immobilisation has been extensively examined, intramuscular connective tissue, particularly endomysium, has been largely neglected: does endomysium content of the soleus muscle increase during bed rest? What is the main finding and its importance? Absolute endomysium content did not change, and previous studies reporting an increase are explicable by muscle fibre atrophy. It must be expected that even a relative connective tissue accumulation will lead to an increase in muscle stiffness.

Abstract: Muscle fibres atrophy during conditions of disuse.

N471D WASH complex subunit strumpellin knock-in mice display mild motor and cardiac abnormalities and BPTF and KLHL11 dysregulation in brain tissue.

Aims: We investigated N471D WASH complex subunit strumpellin (Washc5) knock-in and Washc5 knock-out mice as models for hereditary spastic paraplegia type 8 (SPG8).

Methods: We generated heterozygous and homozygous N471D Washc5 knock-in mice and subjected them to a comprehensive clinical, morphological and laboratory parameter screen, and gait analyses. Brain tissue was used for proteomic analysis.

Dual Functional States of R406W-Desmin Assembly Complexes Cause Cardiomyopathy With Severe Intercalated Disc Derangement in Humans and in Knock-In Mice.

Background: Mutations in the human desmin gene cause myopathies and cardiomyopathies. This study aimed to elucidate molecular mechanisms initiated by the heterozygous R406W-desmin mutation in the development of a severe and early-onset cardiac phenotype.

Methods: We report an adolescent patient who underwent cardiac transplantation as a result of restrictive cardiomyopathy caused by a heterozygous R406W-desmin mutation.

Heart failure after pressure overload in autosomal-dominant desminopathies: Lessons from heterozygous DES-p.R349P knock-in mice.

Background: Mutations in the human desmin gene (DES) cause autosomal-dominant and -recessive cardiomyopathies, leading to heart failure, arrhythmias, and AV blocks. We analyzed the effects of vascular pressure overload in a patient-mimicking p.R349P desmin knock-in mouse model that harbors the orthologue of the frequent human DES missense mutation p.

CRN2 binds to TIMP4 and MMP14 and promotes perivascular invasion of glioblastoma cells.

CRN2 is an actin filament binding protein involved in the regulation of various cellular processes including cell migration and invasion. CRN2 has been implicated in the malignant progression of different types of human cancer. We used CRN2 knock-out mice for analyses as well as for crossbreeding with a Tp53/Pten knock-out glioblastoma mouse model.

Imbalances in protein homeostasis caused by mutant desmin.

Aims: We investigated newly generated immortalized heterozygous and homozygous R349P desmin knock-in myoblasts in conjunction with the corresponding desminopathy mice as models for desminopathies to analyse major protein quality control processes in response to the presence of R349P mutant desmin.

Methods: We used hetero- and homozygous R349P desmin knock-in mice for analyses and for crossbreeding with p53 knock-out mice to generate immortalized R349P desmin knock-in skeletal muscle myoblasts and myotubes. Skeletal muscle sections and cultured muscle cells were investigated by indirect immunofluorescence microscopy, proteasomal activity measurements and immunoblotting addressing autophagy rate, chaperone-assisted selective autophagy and heat shock protein levels.

The heterozygous R155C VCP mutation: Toxic in humans! Harmless in mice?

Heterozygous missense mutations in the human VCP gene cause inclusion body myopathy associated with Paget disease of bone and fronto-temporal dementia (IBMPFD) and amyotrophic lateral sclerosis (ALS). The exact molecular mechanisms by which VCP mutations cause disease manifestation in different tissues are incompletely understood. In the present study, we report the comprehensive analysis of a newly generated R155C VCP knock-in mouse model, which expresses the ortholog of the second most frequently occurring human pathogenic VCP mutation.

Genetic analysis of VCP and WASH complex genes in a German cohort of sporadic ALS-FTD patients.

Mutations of the human valosin-containing protein, p97 (VCP) and Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) complex genes cause motor neuron and cognitive impairment disorders. Here, we analyzed a cohort of German patients with sporadic amyotrophic lateral sclerosis and frontotemporal lobar degeneration comorbidity (ALS/FTD) for VCP and WASH complex gene mutations. Next-generation panel sequencing of VCP, WASH1, FAM21C, CCDC53, SWIP, strumpellin, F-actin capping protein of muscle Z-line alfa 1 (CAPZA1), and CAPZB genes was performed in 43 sporadic ALS/FTD patients.

Mutant desmin substantially perturbs mitochondrial morphology, function and maintenance in skeletal muscle tissue.

Secondary mitochondrial dysfunction is a feature in a wide variety of human protein aggregate diseases caused by mutations in different proteins, both in the central nervous system and in striated muscle. The functional relationship between the expression of a mutated protein and mitochondrial dysfunction is largely unknown. In particular, the mechanism how this dysfunction drives the disease process is still elusive.

Coronin 1C-free primary mouse fibroblasts exhibit robust rearrangements in the orientation of actin filaments, microtubules and intermediate filaments.

Coronin 1C is an established modulator of actin cytoskeleton dynamics. It has been shown to be involved in protrusion formation, cell migration and invasion. Here, we report the generation of primary fibroblasts from coronin 1C knock-out mice in order to investigate the impact of the loss of coronin 1C on cellular structural organisation.

Preservation of vascular tissue under hypothermic conditions.

Background: Preservation of vascular tissue plays a crucial role in the success of organ transplantation. We investigated and compared the performance of 4 preservation solutions at preserving vascular tissue over 24, 48, and 72 h under hypothermic conditions.

Materials And Methods: Rat aortic segments were stored in University of Wisconsin (UW), Modified University of Wisconsin (mUW), EuroCollins (EC), and Bretschneider Histidine-tryptophan-ketoglutarate (HTK) solutions at 4 degrees C for 24, 48, and 72 h.

Prevention of experimental myointimal hyperplasia by immunomodulation.

Introduction: we have tested the hypothesis that treatment with a mycobacterial preparation that modulates the antibody response, would diminish restenosis in a rat angioplasty model.

Materials/methods: male Sprague-Dawley rats were used. All immunisations were given subcutaneously.

Does vascular stapling improve compliance of vascular anastomoses?

Elastic properties of vessel walls are altered by vascular anastomoses. Such alterations may lead to neointimal hyperplasia, which is a common cause of reocclusion following vascular surgery. The severity of paraanastomotic hypercompliant zones and anastomotic compliance drop depend on suturing material and on elastic properties of the anastomotic vessel segments.

Myocardial injury in major aortic surgery.

Purpose: The purpose of this study was to examine the effects of major aortic surgery and its associated oxidative stress and injury on the myocardium.

Methods: Plasma from 27 patients who underwent thoracoabdominal aortic aneurysm (TAAA) repair and 17 patients who underwent infrarenal aortic aneurysm (AAA) repair was collected at incision, aortic crossclamping, and reperfusion and 1, 8, and 24 hours thereafter. Samples were assayed for the myocardial specific protein troponin-T, total antioxidant status, and lipid hydroperoxides.

Endotoxemia during supraceliac aortic crossclamping is associated with suppression of the monocyte CD14 mechanism: possible role of transforming growth factor-beta1.

Purpose: Monocyte CD14 and its soluble form (sCD14) mediate the proinflammatory response to endotoxemia. The aim of this study was to measure the changes to these factors after major aortic surgery and the possible inhibitory role of transforming growth factor-beta(1) (TGF-beta(1)) during these procedures.

Methods: Twenty-four patients with supraceliac aortic crossclamping during thoracoabdominal aortic aneurysm (TAAA) repair and 12 patients with infrarenal aortic crossclamping as part of infrarenal aneurysm repair (AAA) were studied.

[Whiplash injuries of the cervical spine. Neurologic contribution to diagnosis. Therapy and expert evaluation].

The cervical spine is an extremely complex functional unit and has always been the subject of impassioned discussions among surgeons, orthopedic specialists and neurologists. In the presence of injuries affecting this section of the spine, which sometimes have grave consequences--including implications for legal insurance aspects, neurologists are usually at the end of the line when it comes to diagnosis and treatment. In fact, in view of the clinical and technical neurophysiological options available to neurologists, it would be desirable for them to be involved as early as possible.

Deuterium oxide-based University of Wisconsin solution improves viability of hypothermically stored vascular tissue.

Background: Preservation of vascular function largely determines the outcome of transplantation. We have investigated replacing the water (H2O) in University of Wisconsin (UW) solution with deuterium oxide (D2O) in an attempt to improve vascular function after hypothermic storage.

Methods: Rat aortic segments were stored in UW solutions based on 100% H2O, 25% D2O, 50% D2O, and 100% D2O at 4 degrees C for 24, 48, or 72 hr.