Four cases of audio-vestibular disorders related to immunisation with SARS-CoV-2 mRNA vaccines.

To gain medical insight into the clinical course and safety of otolaryngologic disorders following immunisation with severe acute respiratory coronavirus (SARS-CoV-2) mRNA-based vaccines. Case description. We report four cases of transient audio-vestibular symptoms, which occurred shortly after inoculation of two BNT162b2 (Pfizer-BioNTech <sup>®</sup> ) and mRNA-1273 (Moderna®) vaccines. Hearing loss was unilateral in all cases and recovered at least partially: it was associated with persistent gait instability in two cases, after 1 and 7 months. Trigger mechanisms underpinning audio-vestibular impairment remain uncertain. Immune tolerance mechanisms with off-target innate activation of T-lymphocytes may be involved in vestibulocochlear nerve disorders, as for other cranial nerves involvement. The occurrence of audio-vestibular manifestations following mRNA-based vaccines needs ENT monitoring to support their causality in such rare vaccine-related adverse events. Audio-vestibular disorders appeared of transitory nature, including hearing loss, and should not deter further efforts in large-scale vaccination campaigns against SARS-CoV-2

Pharmacovigilance - Vaccins à ARNm contre le Covid-19 : le point sur les effets indésirables [Pharmacovigilance - mRNA COVID-19 vaccines : current state of knowledge on their adverse effects]

The COVID-19 pandemic has stimulated the rapid development and large-scale use of technologically innovative vaccines, such as the mRNA vaccines Spikevax (Moderna) and Comirnaty (Pfizer-BioNTech). This unprecedented deployment has challenged pharmacovigilance, requiring combined skills in safety monitoring, prompt data analysis and continuous dissemination of knowledge. Main recognised adverse events of these vaccines are moderate and transient, linked to their significant reactogenicity. Active post-marketing surveillance has identified rare adverse events such as myopericarditis and a variety of skin reactions. A number of potential rare adverse events are being evaluated and could be retained at the individual level, but do not question the overall safety of these vaccines

COMMD1-deficient dogs accumulate copper in hepatocytes and provide a good model for chronic hepatitis and fibrosis

New therapeutic concepts developed in rodent models should ideally be evaluated in large animal models prior to human clinical application. COMMD1-deficiency in dogs leads to hepatic copper accumulation and chronic hepatitis representing a Wilson's disease like phenotype. Detailed understanding of the pathogenesis and time course of this animal model is required to test its feasibility as a large animal model for chronic hepatitis. In addition to mouse models, true longitudinal studies are possible due to the size of these dogs permitting detailed analysis of the sequence of events from initial insult to final cirrhosis. Therefore, liver biopsies were taken each half year from five new born COMMD1-deficient dogs over a period of 42 months. Biopsies were used for H&E, reticulin, and rubeanic acid (copper) staining. Immunohistochemistry was performed on hepatic stellate cell (HSC) activation marker (alpha-smooth muscle actin, α-SMA), proliferation (Ki67), apoptosis (caspase-3), and bile duct and liver progenitor cell (LPC) markers keratin (K) 19 and 7. Quantitative RT-PCR and Western Blots were performed on gene products involved in the regenerative and fibrotic pathways. Maximum copper accumulation was reached at 12 months of age, which coincided with the first signs of hepatitis. HSCs were activated (α-SMA) from 18 months onwards, with increasing reticulin deposition and hepatocytic proliferation in later stages. Hepatitis and caspase-3 activity (first noticed at 18 months) increased over time. Both HGF and TGF-β1 gene expression peaked at 24 months, and thereafter decreased gradually. Both STAT3 and c-MET showed an increased time-dependent activation. Smad2/3 phosphorylation, indicative for fibrogenesis, was present at all time-points. COMMD1-deficient dogs develop chronic liver disease and cirrhosis comparable to human chronic hepatitis, although at much higher pace. Therefore they represent a genetically-defined large animal model to test clinical applicability of new therapeutics developed in rodent models

Козацькі могили у творчості Тараса Шевченка

The detoxification of ammonia occurs mainly through conversion of ammonia to urea in the liver via the urea cycle and glutamine synthesis. Congenital portosystemic shunts (CPSS) in dogs cause hyperammonemia eventually leading to hepatic encephalopathy. In this study, the gene expression of urea cycle enzymes (carbamoylphosphate synthetase (CPS1), ornithine carbamoyltransferase (OTC), argininosuccinate synthetase (ASS1), argininosuccinate lyase (ASL), and arginase (ARG1)), N-acetylglutamate synthase (NAGS), Glutamate dehydrogenase (GLUD1), and glutamate-ammonia ligase (GLUL) was evaluated in dogs with CPSS before and after surgical closure of the shunt. Additionally, immunohistochemistry was performed on urea cycle enzymes and GLUL on liver samples of healthy dogs and dogs with CPSS to investigate a possible zonal distribution of these enzymes within the liver lobule and to investigate possible differences in distribution in dogs with CPSS compared to healthy dogs. Furthermore, the effect of increasing ammonia concentrations on the expression of the urea cycle enzymes was investigated in primary hepatocytes in vitro. Gene-expression of CPS1, OTC, ASL, GLUD1 and NAGS was down regulated in dogs with CPSS and did not normalize after surgical closure of the shunt. In all dogs GLUL distribution was localized pericentrally. CPS1, OTC and ASS1 were localized periportally in healthy dogs, whereas in CPSS dogs, these enzymes lacked a clear zonal distribution. In primary hepatocytes higher ammonia concentrations induced mRNA levels of CPS1. We hypothesize that the reduction in expression of urea cycle enzymes, NAGS and GLUD1 as well as the alterations in zonal distribution in dogs with CPSS may be caused by a developmental arrest of these enzymes during the embryonic or early postnatal phase

Piezoresistive cantilever designed for torque magnetometry

New piezoresistive silicon cantilevers designed specifically for torque magnetometry on microscopic samples have been microfabricated and tested. These levers have been optimized to detect the torque in two directions corresponding to flexion and torsion. Torque resolution of 10 E-14 N m can be achieved depending on the operating mode. In one version an integrated loop allows an absolute calibration of the device with an accuracy of ~1%. This loop can also be used to excite the lever mechanically. One application is the determination of the mass of nanogram samples by measuring the resonance frequency shift (nanobalance)

An innovative ethosuximide granule formulation designed for pediatric use: Comparative pharmacokinetics, safety, tolerability, and palatability profile versus reference syrup.

Ethosuximide, the first-line therapy for childhood absence epilepsy, is currently formulated as a syrup (Zarontin®, Pfizer) with a bitter taste and high sugar content, poorly adapted to children, and a ketogenic diet. The collaborative European FP7 project KIEKIDS aimed at developing an innovative sugar-free, tasteless formulation convenient for pediatric use. This dual Phase-I study evaluated two granule formulations based on lipid multiparticulate (LMP) technology. Two panels of 6 healthy adult volunteers underwent a randomized, placebo-controlled, partly blinded, 3-way cross-over trial, comparing ethosuximide granules A or B with placebo granules and syrup at single 10 mg/kg doses. Corresponding plasma pharmacokinetic profiles of ethosuximide were compared, along with palatability, safety, and tolerability. The LMP granule A proved suboptimal due to bitterness and adherence to beaker walls, while the optimized granule B revealed excellent palatability, similar to placebo granules, and low adherence to glass. The relative bioavailability of granules A versus syrup, based on dose-normalized C <sub>max</sub> and AUC <sub>0-∞</sub> was 93.7% [90% CI: 76.3-115.1] and 96.1% [91.0-101.5], respectively. For granules B it was 87.6% [81.6-94.0] and 92.5% [88.5-96.6], respectively, with slightly delayed t <sub>max</sub> of 0.75 h [0.5-4.05] compared to syrup 0.5 h [0.3-0.8]. Tolerability visual analog scales revealed a trend for statistically non-significant improvement versus syrup at peak (30 min) for transient dizziness (both granules), fatigue (granules A), and anxiety (granules B). The innovative ethosuximide granule formulation B achieves a suitable profile for pediatric use, being sugar-free, tasteless, bioequivalent, and well-tolerated while enabling precise adjustment to body weight

Creating a learning space: Using experiential learning and creativity in the teaching and learning of social pedagogy

This reflective account has been co-developed, produced and written by students and the teaching staff on the BA Hons Social Pedagogy, Advocacy, and Participation degree at the University of Central Lancashire. The account focuses on the use of experiential and creative teaching methods utilised on the course and how this enhances the understanding and application of social pedagogy. The article critically analyses the link between how the social pedagogical theories, concepts and methods are taught and the advancement of the student and lecturer understanding of this field of study. In developing this reflective account, the current student cohort and lecturers were given the opportunity to participate in a collaborative reflection across all years of the course. They discussed their own learning journey and how this has shaped development of creativity within their practice. During the discussions around the use of blended, experiential learning and creativity, three key themes emerged: (1) the importance of the environment on creativity and learning; (2) the importance of relationships, creativity and learning; and (3) Haltung, psychological safety and creativity. In the reflections on what they have learned so far, the students and lecturers hope to inspire other education providers to use creative and experiential teaching methods within their courses. The authors feel that the reflective account contains useful information around the learning that has taken place over the last three years of this course being taugh

Two cases of "cannabis acute psychosis" following the administration of oral cannabis

BACKGROUND: Cannabis is the most commonly used illegal drug and its therapeutic aspects have a growing interest. Short-term psychotic reactions have been described but not clearly with synthetic oral THC, especially in occasional users. CASE PRESENTATIONS: We report two cases of healthy subjects who were occasional but regular cannabis users without psychiatric history who developed transient psychotic symptoms (depersonalization, paranoid feelings and derealisation) following oral administration of cannabis. In contrast to most other case reports where circumstances and blood concentrations are unknown, the two cases reported here happened under experimental conditions with all subjects negative for cannabis, opiates, amphetamines, cocaine, benzodiazepines and alcohol, and therefore the ingested dose, the time-events of effects on behavior and performance as well as the cannabinoid blood levels were documented. CONCLUSION: While the oral route of administration achieves only limited blood concentrations, significant psychotic reactions may occur

Social Pedagogy: An Approach Without Fixed Recipes

A historical and theoretical reconstruction of the specificity and peculiarity of the discipline of social pedagogy, as it has developed in Denmark. Social pedagogy takes its departure from the idea that the individual person and the community are complementary but at the same time opposed to each other, so the task of social pedagogy is rebalancing the dynamics between the two. Social pedagogy is also characterised as a discipline with three dimensions: a practical dimension, a theoretical dimension and a professional dimension. The professional’s task is neither to apply theory in practice nor to uphold the usual practice; it is to mediate between theory and practice. The specificity of the discipline gives rise to particular challenges and dilemmas that theorists make understandable and transparent and practitioners have to deal with. A big challenge for social pedagogy is the quest for evidence-based methods that overrides the specificity of the social pedagogical approach. Balancing different forms of knowledge implies that programmes and methods are used as inspiration that can be contained in a social pedagogical approach