Virus-mediated delivery of single-chain antibody targeting TDP-43 protects against neuropathology, cognitive impairment and motor deficit caused by chronic cerebral hypoperfusion.

Chronic cerebral hypoperfusion induced by permanent unilateral common carotid artery occlusion in mice was recently found to induce an age-dependent formation of insoluble cytoplasmic TDP-43 aggregates reminiscent of pathological changes found in human vascular dementia. In this model, the gradual deregulation of TDP-43 homeostasis in cortical neurons was associated with marked cognitive and motor deficits. To target the TDP-43-mediated toxicity in this model, we generated an adeno-associated virus vector encoding a single-chain antibody against TDP-43, called scFv-E6, designed for pan-neuronal transduction following intravenous administration.

Safety and efficacy of intrathecal antibodies to Nogo-A in patients with acute cervical spinal cord injury: a randomised, double-blind, multicentre, placebo-controlled, phase 2b trial.

Background: Spinal cord injury results in permanent neurological impairment and disability due to the absence of spontaneous regeneration. NG101, a recombinant human antibody, neutralises the neurite growth-inhibiting protein Nogo-A, promoting neural repair and motor recovery in animal models of spinal cord injury. We aimed to evaluate the efficacy of intrathecal NG101 on recovery in patients with acute cervical traumatic spinal cord injury.

Muscle Excitability Scale for the assessment of spastic reflexes in spinal cord injury: development and evaluation.

Study Design: A psychometric study.

Objectives: To introduce a novel simple tool designed to evaluate the intensity of the phasic (dynamic) component of spastic motor behavior in spinal cord injury (SCI) people and to assess its reliability and validity.

Setting: The study was developed in the Spinal Cord Unit at University Hospital Motol and Paraple Centre in Prague, Czech Republic.

Inhibition of NF-κB with an Analog of Withaferin-A Restores TDP-43 Homeostasis and Proteome Profiles in a Model of Sporadic ALS.

The current knowledge on pathogenic mechanisms in amyotrophic lateral sclerosis (ALS) has widely been derived from studies with cell and animal models bearing ALS-linked genetic mutations. However, it remains unclear to what extent these disease models are of relevance to sporadic ALS. Few years ago, we reported that the cerebrospinal fluid (CSF) from sporadic ALS patients contains toxic factors for disease transmission in mice via chronic intracerebroventricular (i.

Chronically activated microglia in ALS gradually lose their immune functions and develop unconventional proteome.

Neuroinflammation and chronic activation of microglial cells are the prominent features of amyotrophic lateral sclerosis (ALS) pathology. While alterations in the mRNA profile of diseased microglia have been well documented, the actual microglia proteome remains poorly characterized. Here we performed a functional characterization together with proteome analyses of microglial cells at different stages of disease in the SOD1-G93A model of ALS.

Faecal microbiota transplantation for multidrug-resistant organism decolonization in spinal cord injury patients: a case series.

Introduction: The increase of multidrug-resistant (MDR) bacteria in healthcare settings is a worldwide concern. Isolation precautions must be implemented to control the significant risk of transmitting these pathogens among patients. Antibiotic decolonization is not recommended because of the threat of increasing antibiotic resistance.

Targeting SRSF3 restores immune mRNA translation in microglia/macrophages following cerebral ischemia.

We recently described a novel ribosome-based regulatory mechanism/checkpoint that controls innate immune gene translation and microglial activation in non-sterile inflammation orchestrated by RNA binding protein SRSF3. Here we describe a role of SRSF3 in the regulation of microglia/macrophage activation phenotypes after experimental stroke. Using a model-system for analysis of the dynamic translational state of microglial ribosomes we show that 24 h after stroke highly upregulated immune mRNAs are not translated resulting in a marked dissociation of mRNA and protein networks in activated microglia/macrophages.

Translational profiling identifies sex-specific metabolic and epigenetic reprogramming of cortical microglia/macrophages in APPPS1-21 mice with an antibiotic-perturbed-microbiome.

Background: Microglia, the brain-resident macrophages perform immune surveillance and engage with pathological processes resulting in phenotype changes necessary for maintaining homeostasis. In preceding studies, we showed that antibiotic-induced perturbations of the gut microbiome of APPPS1-21 mice resulted in significant attenuation in Aβ amyloidosis and altered microglial phenotypes that are specific to male mice. The molecular events underlying microglial phenotypic transitions remain unclear.

Epidural spinal cord stimulation can facilitate ejaculatory response in spinal cord injury individuals: a report of two cases.

Background: The recovery of autonomic functions and the ability to reproduce in particular is of the highest priority to individuals with spinal cord injury (SCI). The potential of epidural spinal cord stimulation (ESCS) for promoting recovery of sensorimotor functions in the chronic phase of SCI has long been studied. In recent years, several studies have emerged confirming the positive effect of ESCS also on the cardiovascular system and neurogenic bladder and bowel.

Emerging Trends in the Field of Inflammation and Proteinopathy in ALS/FTD Spectrum Disorder.

Proteinopathy and neuroinflammation are two main hallmarks of neurodegenerative diseases. They also represent rare common events in an exceptionally broad landscape of genetic, environmental, neuropathologic, and clinical heterogeneity present in patients. Here, we aim to recount the emerging trends in amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) spectrum disorder.

Radiation doses to mediastinal organs at risk in early-stage unfavorable Hodgkin lymphoma- a risk stratified analysis of the GHSG HD17 trial.

Introduction: The German Hodgkin Study Group (GHSG) HD17 trial established the omission of radiotherapy (RT) for patients with early-stage unfavorable Hodgkin lymphoma being PET-negative after 2 cycles of BEACOPP escalated plus 2 cycles of ABVD. This patient group reveals heterogeneity in characteristics and disease extent which prompted us to perform a decisive dosimetric analysis according to GHSG risk factors. This may help to tailor RT individually balancing risks and benefits.

Walking Outcome After Traumatic Paraplegic Spinal Cord Injury: The Function of Which Myotomes Makes a Difference?

Background: Accurate prediction of walking function after a traumatic spinal cord injury (SCI) is crucial for an appropriate tailoring and application of therapeutical interventions. Long-term outcome of ambulation is strongly related to residual muscle function acutely after injury and its recovery potential. The identification of the underlying determinants of ambulation, however, remains a challenging task in SCI, a neurological disorder presented with heterogeneous clinical manifestations and recovery trajectories.

IsletSwipe, a mobile platform for expert opinion exchange on islet graft images.

We previously developed a deep learning-based web service (IsletNet) for an automated counting of isolated pancreatic islets. The neural network training is limited by the absent consensus on the ground truth annotations. Here, we present a platform (IsletSwipe) for an exchange of graphical opinions among experts to facilitate the consensus formation.

Distinct Plasma Immune Profile in ALS Implicates sTNFR-II in pAMPK/Leptin Homeostasis.

Amyotrophic lateral sclerosis (ALS) is a clinically highly heterogeneous disease with a survival rate ranging from months to decades. Evidence suggests that a systemic deregulation of immune response may play a role and affect disease progression. Here, we measured 62 different immune/metabolic mediators in plasma of sporadic ALS (sALS) patients.

[First Experience with Diaphragm Pacing System in the Czech Republic].

Patients with impaired diaphragm function are dependent on long-term mechanical ventilation. It is associated with numerous health complications as well as significant economic burden. Intramuscular diaphragm stimulation through laparoscopic implantation of pacing electrodes is a safe method which enables restoring breathing using diaphragm in a considerable number of patients.

Effect of High School Showcase Exposures and Timing of Ulnar Collateral Ligament Tear on Professional Baseball Careers in Elite Pitchers.

Background: Showcase participation has been considered a risk factor for elbow injuries. It remains unclear whether high school (HS) showcase volume negatively affects pitchers' career paths. Because pitchers are achieving 90 mph thresholds at younger ages, it is unknown whether shorter time intervals between achieving 90 mph thresholds and dates of ulnar collateral ligament reconstruction (UCL-R), known as time to tear (TTT), may affect career trajectory.

CD36 neutralisation blunts TLR2-IRF7 but not IRF3 pathway in neonatal mouse brain and immature human microglia following innate immune challenge.

Innate immune response in neonatal brain is associated with a robust microglial activation and induction of Toll-like Receptors (TLRs). To date, the role of the scavenger receptor CD36 in TLRs modulation, particularly TLR2 signaling, has been well established in adult brain. However, the crosstalk between TLR4, TLR2 and CD36 and its immunogenic influence in the neonatal brain remains unclear.

Therapeutic Trial of anle138b in Mouse Models of Genetic Prion Disease.

Phenotypic screening has yielded small-molecule inhibitors of prion replication that are effective against certain prion strains but not others. Here, we sought to test the small molecule anle138b in multiple mouse models of prion disease. In mice inoculated with the RML strain of prions, anle138b doubled survival and durably suppressed astrogliosis measured by live-animal bioluminescence imaging.

Ulnar Collateral Ligament Tear in Elite Baseball Pitchers: Are High School Showcase Exposures Associated With Injury?

Background: Ulnar collateral ligament reconstruction (UCLR) surgeries have increased significantly in amateur and professional baseball pitchers. Although showcase participation has been considered an injury risk factor, limited data are available to corroborate this association.

Hypothesis: Elite pitchers achieving fastball velocities ≥90, ≥92, and ≥95 mph at younger ages would be more likely to undergo UCLR earlier in their careers compared with pitchers not achieving these velocity thresholds at younger ages.

Bilateral Mature Ovarian Teratoma with Torsion in a Premenarchal Girl.

Mature cystic teratoma is the most common type of ovarian tumor in children. Adnexal torsion is the main complication of mature ovarian teratoma. The synchronous bilateral incidence of mature cystic teratoma in premenarchal girls is known to be rare.