Acute flaccid myelitis in Switzerland - association with enterovirus D68.

Poliomyelitis-like acute flaccid myelitis associated with enterovirus D68 (EV-D68) has emerged globally during the past decade. Here we describe the first documented case reported from Switzerland, and a second, suspected case occurring in temporal association. AFM occurs primarily in children, is usually heralded by a febrile, respiratory prodrome followed by acute-onset, usually asymmetrical, limb weakness with some predilection for the upper extremities, and respiratory muscle compromise in one third of reported cases. There is no specific therapy and the majority of cases result in permanent neurological sequelae. A comprehensive diagnostic workup and timely reporting to the health authorities are essential. Surveillance of respiratory and stool samples for EV-D68 and other neurotropic enteroviruses is in place in several European countries and warrants consideration in Switzerland. This could entail the extension of the poliomyelitis surveillance program of the Federal Office of Public Health by monitoring and enteroviral typing of respiratory samples from patients with acute flaccid paralysis

Long-term sequelae after acquired pediatric hemorrhagic cerebellar lesions

Purpose: The aim of the present study was to assess cognitive, affective, and motor long-term sequelae after acquired focal pediatric cerebellar lesions. Methods: Eight patients with a history of isolated acquired hemorrhagic cerebellar lesions before the age of 13 participated in this study. All participants underwent a neurologic examination, including the Zurich Neuromotor Assessment (ZNA) and the International Cooperative Ataxia Rating Scale (ICARS). Cognitive functions have been evaluated with a general cognitive assessment and an extensive neuropsychological battery. Furthermore, patients and parents filled in questionnaires about quality of life and possible behavioral or emotional problems. Results: The results revealed that all patients exhibited motor problems (ZNA). Most participants had further restricted oculomotor movements (ICARS). Age at injury and the full scale IQ were significantly positively correlated (Pearson correlation 0.779; p = 0.023). Conversely, no overall neuropsychological profile could be identified except for marginally reduced reaction times and susceptibility to interference. In addition, borderline results in semantic and phonemic word fluency tasks were apparent. A dysexecutive syndrome was diagnosed in one patient. However, verbal performance and reading abilities were non-pathologic in all participants. The patients reported having a good quality of life without major physical restrictions. Conclusions: Emotional disturbances and the presence of a mild cerebellar cognitive affective syndrome (as frequently described in adult patients) could only be confirmed in adolescents with vermis lesions. Nevertheless, in laboratory conditions, neuropsychological impairments were present in all patients. Heterogeneity of age at injury and exact lesion site may have led to interpersonal differences in neuropsychological outcom

Characteristic retinal atrophy pattern allows differentiation between pediatric MOGAD and MS after a single optic neuritis episode

Optical coherence tomography; Optic neuritis; Pediatric patientsTomografía de coherencia óptica; Neuritis óptica; Pacientes pediátricosTomografia de coherència òptica; Neuritis òptica; Pacients pediàtricsBackground Optic neuritis (ON) is the most prevalent manifestation of pediatric multiple sclerosis (MSped) and myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGADped) in children > 6 years. In this study, we investigated retinal atrophy patterns and diagnostic accuracy of optical coherence tomography (OCT) in differentiating between both diseases after the first ON episode. Methods Patients were retrospectively identified in eight tertial referral centers. OCT, VEP and high/low-contrast visual acuity (HCVA/LCVA) have been investigated > 6 months after the first ON. Prevalence of pathological OCT findings was identified based on data of 144 age-matched healthy controls. Results Thirteen MOGADped (10.7 ± 4.2 years, F:M 8:5, 21 ON eyes) and 21 MSped (14.3 ± 2.4 years, F:M 19:2, 24 ON eyes) patients were recruited. We observed a significantly more profound atrophy of both peripapillary and macular retinal nerve fiber layer in MOGADped compared to MSped (pRNFL global: 68.2 ± 16.9 vs. 89.4 ± 12.3 µm, p < 0.001; mRNFL: 0.12 ± 0.01 vs. 0.14 ± 0.01 mm3, p < 0.001). Neither other macular layers nor P100 latency differed. MOGADped developed global atrophy affecting all peripapillary segments, while MSped displayed predominantly temporal thinning. Nasal pRNFL allowed differentiation between both diseases with the highest diagnostic accuracy (AUC = 0.902, cutoff < 62.5 µm, 90.5% sensitivity and 70.8% specificity for MOGADped). OCT was also substantially more sensitive compared to VEP in identification of ON eyes in MOGAD (pathological findings in 90% vs. 14%, p = 0.016). Conclusion First MOGAD-ON results in a more severe global peripapillary atrophy compared to predominantly temporal thinning in MS-ON. Nasal pRNFL allows differentiation between both diseases with the highest accuracy, supporting the additional diagnostic value of OCT in children with ON.Open Access funding enabled and organized by Projekt DEAL. No

Osteogenic differentiation of MG63 cells in biodegradable scaffolds based on gelatin and genipin

Gelatin is a denatured collagen and commercially available as a biodegradable polymer. It has been extensively utilized for pharmaceutical and medical purposes, and its biosafety has been proven through long clinical applications. It showed an high cell attachment and proliferation, thus it has been widely considered as one of the best material to be used in medicine regenerative. Scaffolds based on pure gelatin showed a low mechanical and biological stability, so that a chemical crosslinking is necessary to improve its mechanical proprieties and success in clinical application. The aim of this study was to test the influence of a new porous composite scaffold based on gelatin/genipin composition on cell adhesion, proliferation and osteogenic potential. Genipin is a natural non toxic crosslinking agent which significantly improve the mechanical stability of the scaffold1. Osteoblast like cell (MG63) were seeded in collagen/genipin scaffolds for 24h, 7, 14, 21 and 28 days. Cell proliferation assay, light and electron microscopy analysis were performed to evaluate cell growth and morphological changes induced by cell/ scaffold interactions. Real Time PCR were carried out to evaluate the expression of the osteogenic markers such as collagen type I, osteonectin, osteopontin, ostecalcin and alkaline phosphatase proteins in MG63 seeded on gelatin/genipin scaffolds. Our results showed that gelatin/genipin scaffold is an excellent substrate for the growth and cell proliferation. Microscopy analysis showed an high cell adhesion on scaffold surface and an deep penetration in the macropores of the sponge. The Real Time data reveal a significant difference in the expression of the ostegenic markers in MG63 grown on gelatin/genipin scaffold compared to control samples. In conclusion, our data demonstrated that gelatin/genipin scaffold showed an high biocompatibility with human cells and an high osteogenic potential and it could be a potential tool in regenerative medicine

Fatigue in Post-COVID-19 Syndrome: Clinical Phenomenology, Comorbidities and Association With Initial Course of COVID-19.

Introduction Post-COVID-19 syndrome affects approximately 10-25% of people suffering from COVID-19 infection, irrespective of initial COVID-19 severity. Fatigue is one of the major symptoms, occurring in 30-90% of people with post-COVID-19 syndrome. This study aims at describing factors associated with fatigue in people with Post-COVID-19 seen in our newly established Post-Covid clinic. Methods This retrospective single center study included 42 consecutive patients suffering from Post-COVID-19 syndrome treated at the Department of Neurology, University Hospital Bern, between 11/2020 and05/2021. Clinical phenomenology of Post-COVID-19 syndrome with a special focus on fatigue and risk factor identification was performed using Mann-Whitney U Test, Pearson Correlation, and Chi-Quadrat-Test. Results Fatigue (90.5%) was the most prevalent Post-COVID-19 symptom followed by depressive mood (52.4%) and sleep disturbance (47.6%). Fatigue was in mean severe (Fatigue severity scale (FSS) mean 5.5 points (95% Confidence interval (95CI) 5.1 - 5.9, range .9 - 6.9, n = 40), and it was unrelated to age, COVID-19 severity or sex. The only related factors with fatigue severity were daytime sleepiness and depressed mood. Conclusion Fatigue is the main symptom of the Post-COVID-19 syndrome in our cohort. Further studies describing this syndrome are needed to prepare the healthcare systems for the challenge of treating patients with Post-COVID-19 syndrome

Evaluation of diagnostic criteria and red flags of myelin oligodendrocyte glycoprotein encephalomyelitis in a clinical routine cohort.

AIMS Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) have been proposed to define "MOG encephalomyelitis" (MOG-EM), with published diagnostic and "red flag" criteria. We aimed to evaluate these criteria in a routine clinical setting. METHODS We retrospectively analyzed patients with borderline/positive MOG-IgG and applied the diagnostic and red flag criteria to determine likelihood of MOG-EM diagnosis. Para-/clinical parameters were described and analyzed with chi-square test. RESULTS In total, 37 patients fulfilled MOG-EM diagnostic criteria (female-to-male ratio: 1.6:1, median onset age: 28.0 years [IQR 18.5-40.5], n = 8 with pediatric onset). In 24/37, red flags were present, predominantly MOG-IgG at assay cutoff and/or MRI lesions suggestive of multiple sclerosis (MS). As proposed in the consensus criteria, these patients should rather be described as "possible" MOG-EM. Of these, we classified 13 patients as "unlikely" MOG-EM in the presence of the red flag "borderline MOG-IgG" with negative MOG-IgG retest or coincidence of ≥1 additional red flag. This group mainly consisted of patients diagnosed with MS (n = 11). Frequency of cerebrospinal fluid (CSF-)-specific oligoclonal bands (OCB) is significantly lower in definite vs possible and unlikely MOG-EM (P = .0005). CONCLUSION Evaluation of diagnostic and red flag criteria, MOG-IgG retesting (incl. change of assay), and CSF-specific OCB are relevant in clinical routine cohorts to differentiate MOG-EM from MS

matricellular protein expression and cell ultrastructure as parameters to test in vitro cytotoxicity of a biomimetic scaffold

Following scaffold implantation, cell sufferance, in-vivo encapsulation, foreign body reaction and inflammatory response has been reported and the up- regulation of matricellular proteins is often connected with this condition. Cytotoxicity of biomaterials is generally tested according to ISO standard 10993-5 based mainly on viability tests. Additional assays, based on improved cytotoxicity knowledge, are suggested in order to better analyze the biocompatibility of implant materials. The purpose of the study was to evaluate the matricellular protein expression as biomarker for in vitro-testing the biocompatibility of implant materials. Tenascin-C, osteocalcin and osteopontin belong to the matricellular protein family and were chosen as cytotoxicity markers. Mesenchymal stem cells were seeded on collagen/hydroxyapatite scaffold and on carboxymethyl cellulose based hydrogel in order to evaluate gene/protein expression by cell viability test, Real Time PCR and western blot. Electron microscopy was carried out to evaluate the morphological changes induced by cell/scaffold interactions. A low expression of tenascin-c, osteonectin and osteopontin was demonstrated in collagen/hydroxyapatite scaffold compared to the cells cultured on tissue flasks and on hydrogel scaffold. Based on our results, we propose matricellular protein expression as parameter for testing in vitro biocompatibility of implant materials

Sistema de Busca de Dados Bionorte: Aproximando, de Forma Colaborativa, as Pesquisas Acadêmicas e a Bioindústria Amazônica

Este texto relata a experiência das ações gerais para o desenvolvimento do Sistema de Busca de Dados Bionorte, uma ferramenta que possibilita aos usuários participarem de forma colaborativa do processo de difusão dos conhecimentos tanto de relevância socioambiental sobre a biodiversidade amazônica quanto do potencial de agregação de valor comercial aos recursos dela advindos. Esta iniciativa decorreu da ausência de ferramentas que integrem o conhecimento científico sobre esta biodiversidade ao mercado, via empresas. O desenvolvimento ocorreu em três ações conjugadas: a concepção científica e empresarial de sua interface; o design de interface do aplicativo juntamente com a programação do servidor e a programação do banco de dados; e a prospecção e inserção dos dados. Durante o estudo, foram cadastradas mais de 526 empresas, 34 instituições de ensino e pesquisa, 1475 pesquisadores, 139 Programas de Pós-graduação, e 99 Cooperativas, com informações interconectadas por uma categoria central: a matéria-prima. Ressalva-se, porém a necessidade de alimentação de novos dados e a contínua validação dos mesmos para que o Sistema de Busca de Dados Bionorte seja preciso, confiável e se torne uma ferramenta para a visibilidade dos atores que têm interesse nos recursos da biodiversidade amazônica

T-cell and serological responses to Erp, an exported Mycobacterium tuberculosis protein, in tuberculosis patients and healthy individuals

<p>Abstract</p> <p>Background</p> <p>The identification of antigens able to differentiate tuberculosis (TB) disease from TB infection would be valuable. Cellular and humoral immune responses to Erp (Exported repetitive protein) – a recently identified <it>M. tuberculosis </it>protein – have not yet been investigated in humans and may contribute to this aim.</p> <p>Methods</p> <p>We analyzed the cellular and humoral immune responses to Erp, ESAT-6, Ag85B and PPD in TB patients, in BCG⁺individuals without infection, BCG⁺individuals with latent TB infection (LTBI) and BCG^-controls. We used lymphoproliferation, ELISpot IFN-γ, cytokine production assays and detection of specific human antibodies against recombinant <it>M. tuberculosis </it>proteins.</p> <p>Results</p> <p>We included 22 TB patients, 9 BCG⁺individuals without TB infection, 7 LTBI and 7 BCG^-controls. Erp-specific T cell counts were higher in LTBI than in the other groups. Erp-specific T cell counts were higher in LTBI subjects than TB patients (median positive frequency of 211 SFC/10⁶PBMC (range 118–2000) for LTBI subjects compared to 80 SFC/10⁶PBMC (range 50–191), p = 0.019); responses to PPD and ESAT-6 antigens did not differ between these groups. IFN-γ secretion after Erp stimulation differed between TB patients and LTBI subjects (p = 0.02). Moreover, LTBI subjects but not TB patients or healthy subjects produced IgG3 against Erp.</p> <p>Conclusion</p> <p>The frequencies of IFN-γ-producing specific T cells, the IFN-γ secretion and the production of IgG3 after Erp stimulation are higher in LTBI subjects than in TB patients, whereas PPD and ESAT-6 are not.</p