Translation and cultural adaptation of the COVID-19 Yorkshire Rehabilitation Scale into German

BackgroundExperts estimate that in up to 10% of the infected, SARS-CoV-2 would cause persistent symptoms, activity limitations and reduced quality of life. Referred to as long COVID, these conditions might, in the future, specifically impact German-speaking countries due to their higher rates of unvaccinated people compared to other Western countries. Accurate measurement of symptom burden and its consequences is needed to manage conditions such as long COVID, and several tools have been developed to do so. However, no patient-reported instrument existed in the German language at the time of writing.ObjectiveThis study, therefore, aimed to develop a German version of the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS).MethodsWe conducted a translation and qualitative evaluation, including cultural adaptation, of the C19-YRS and assessed its face validity. After creating a preliminary version, 26 individuals (14 women [53%]) participated in cognitive interviews (January 2022 to March 2022). Using cognitive debriefing interviews, we ensured the content’s comprehensibility. The matrix-framework method guided the qualitative data analysis.ResultsCompared to the original English version, adaptations were necessary, resulting in changes to the introductory text, while the items for recording persistent symptoms were hardly changed.ConclusionThe German version of the C19-YRS is expected to support standardized long COVID care

Alpha-1 antitrypsin (AAT) augmentation and the liver phenotype of adults with AAT deficiency (genotype Pi*ZZ)

Background and aims: Alpha-1 antitrypsin (AAT) is a major protease inhibitor produced by hepatocytes. The most relevant AAT mutation giving rise to AAT deficiency (AATD), the ‘Pi*Z’ variant, causes harmful AAT protein accumulation in the liver, shortage of AAT in the systemic circulation and thereby predisposes to liver and lung injury. Although intravenous AAT augmentation constitutes an established treatment of AATD-associated lung disease, its impact on the liver is unknown.Methods: Liver-related parameters were assessed in a multinational cohort of 760 adults with severe AATD (Pi*ZZ genotype) and available liver phenotyping, of whom 344 received augmentation therapy and 416 did not. Liver fibrosis was evaluated non-invasively via the serum test AST-to-platelet ratio index (APRI) as well as via transient elastography-based liver stiffness measurement (LSM). Histological parameters were compared in 15 Pi*ZZ adults with and 35 without augmentation.Results: Compared to non-augmented subjects, augmented Pi*ZZ individuals displayed lower serum liver enzyme levels (AST 71 vs. 75 % ULN, PConclusion: The first evaluation of AAT augmentation on the Pi*ZZ-related liver disease indicates liver safety of a widely used treatment for AATD-associated lung disease. Prospective studies are needed to confirm the beneficial effects and to demonstrate the potential efficacy of exogenous AAT in patients with Pi*ZZ-associated liver disease

Bi-allelic Mutations in NDUFA6 Establish Its Role in Early-Onset Isolated Mitochondrial Complex I Deficiency.

Isolated complex I deficiency is a common biochemical phenotype observed in pediatric mitochondrial disease and often arises as a consequence of pathogenic variants affecting one of the ∼65 genes encoding the complex I structural subunits or assembly factors. Such genetic heterogeneity means that application of next-generation sequencing technologies to undiagnosed cohorts has been a catalyst for genetic diagnosis and gene-disease associations. We describe the clinical and molecular genetic investigations of four unrelated children who presented with neuroradiological findings and/or elevated lactate levels, highly suggestive of an underlying mitochondrial diagnosis. Next-generation sequencing identified bi-allelic variants in NDUFA6, encoding a 15 kDa LYR-motif-containing complex I subunit that forms part of the Q-module. Functional investigations using subjects' fibroblast cell lines demonstrated complex I assembly defects, which were characterized in detail by mass-spectrometry-based complexome profiling. This confirmed a marked reduction in incorporated NDUFA6 and a concomitant reduction in other Q-module subunits, including NDUFAB1, NDUFA7, and NDUFA12. Lentiviral transduction of subjects' fibroblasts showed normalization of complex I. These data also support supercomplex formation, whereby the ∼830 kDa complex I intermediate (consisting of the P- and Q-modules) is in complex with assembled complex III and IV holoenzymes despite lacking the N-module. Interestingly, RNA-sequencing data provided evidence that the consensus RefSeq accession number does not correspond to the predominant transcript in clinically relevant tissues, prompting revision of the NDUFA6 RefSeq transcript and highlighting not only the importance of thorough variant interpretation but also the assessment of appropriate transcripts for analysis

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Educational readiness among health professionals in rheumatology : low awareness of EULAR offerings and unfamiliarity with the course content as major barriers – results of a EULAR-funded European survey

Background: Ongoing education of health professionals in rheumatology (HPR) is critical for high-quality care. An essential factor is education readiness and a high quality of educational offerings. We explored which factors contributed to education readiness and investigated currently offered postgraduate education, including the European Alliance of Associations for Rheumatology (EULAR) offerings. Methods and participants: We developed an online questionnaire, translated it into 24 languages and distributed it in 30 European countries. We used natural language processing and the Latent Dirichlet Allocation to analyse the qualitative experiences of the participants as well as descriptive statistics and multiple logistic regression to determine factors influencing postgraduate educational readiness. Reporting followed the Checklist for Reporting Results of Internet E-Surveys guideline. Results: The questionnaire was accessed 3589 times, and 667 complete responses from 34 European countries were recorded. The highest educational needs were ‘professional development’, ‘prevention and lifestyle intervention’. Older age, more working experience in rheumatology and higher education levels were positively associated with higher postgraduate educational readiness. While more than half of the HPR were familiar with EULAR as an association and the respondents reported an increased interest in the content of the educational offerings, the courses and the annual congress were poorly attended due to a lack of awareness, comparatively high costs and language barriers. Conclusions: To promote the uptake of EULAR educational offerings, attention is needed to increase awareness among national organisations, offer accessible participation costs, and address language barriers

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Influence of electromyographic biofeedback on the outcome of rehabilitation of the Musculus quadriceps femoris in patients with knee pathologies

Hintergrund und Ziel: Patient*innen mit Kniegelenkspathologien weisen häufig eine Schwäche sowie verminderte Ansteuerungsfähigkeit des Musculus quadriceps femoris auf. Im Rahmen der Rehabilitation von Kniegelenkspathologien wird in den letzten Jahren Elektromyographisches Biofeedback (EMGBF) zusätzlich zur Visualisierung der Ansteuerung des Quadrizeps während Kräftigungsübungen angewandt. Das Ziel dieser Arbeit ist es herauszufinden, ob die Anwendung von EMGBF im Vergleich zur Rehabilitation ohne dieses Tool, Unterschiede im Outcome zeigt. Methode: Die vorliegende Arbeit basiert auf einer Literaturrecherche, welche in verschiedenen Datenbanken auf Grundlage von vordefinierten Suchbegriffen durchgeführt wurde. Die Suchergebnisse werden anhand von vordefinierten Ein- und Ausschlusskriterien gescreent, wobei nicht relevante Studien ausgeschlossen werden. Für die Beantwortung der Forschungsfrage werden eine Metaanalyse von Xie et al. (2021), ein systematisches Review von Armshaw et al. (2022) sowie zwei systematische Reviews von Raeissadat et al. (2018) und Sklempe Kokic et al. (2022) als auch eine Forschungsarbeit von Hasan et al. (2022) ausgewählt. AMSTAR2 und die PEDro-Skala werden verwendet, um ihre methodische Qualität und ihr Risiko bezüglich Verzerrungen zu bewerten. Ergebnisse: 20 % der in dieser Arbeit inkludierten Studien haben signifikante Messergebnisse zum Parameter Funktionalität des Kniegelenks gemessen. 50 % der Studien liefert für den Messwert Quadrizepsstärke klinisch relevante Ergebnisse, welche für die Verwendung von EMGBF sprechen. 20 % der Studien zeigen eine Signifikanz in der Verbesserung der ROM und 30 % in Punkto Schmerzlinderung innerhalb der Interventionsgruppe im Vergleich zur Kontrollgruppe. Schlussfolgerung: Die Autorin dieser Arbeit schlussfolgert anhand der Ergebnisse, dass EMGBF eine sinnvolle Ergänzung zur Kräftigung des Quadriceps femoris im Rahmen der Rehabilitation darstellen kann. Für die restlichen drei Parameter ROM, Schmerz und Funktionalität des Kniegelenks ist die Evidenz einer klinischen Relevanz geringer. Daher sollten die Verfügbarkeit, das Kosten-Nutzen-Verhältnis und die Präferenzen von Therapeut*in und Patient*in bei der Entscheidung für oder gegen den Einsatz von EMGBF berücksichtigt werden.Background and objective: Patients with knee joint pathologies often show weakness and reduced control of the quadriceps femoris muscle. In recent years, electromyographic biofeedback (EMGBF) has been used in the rehabilitation of knee joint pathologies in addition to visualising the control of the quadriceps during strengthening exercises. The aim of this study is to find out whether the use of EMGBF shows differences in outcome compared to rehabilitation without EMGBF. Methods: The present study is based on a literature search, which was conducted in various databases based on predefined search terms. The search results are screened using predefined inclusion and exclusion criteria, whereby irrelevant studies are excluded. A meta-analysis by Xie et al. (2021), a systematic review by Armshaw et al. (2022) and two sys-tematic reviews by Raeissadat et al. (2018) and Sklempe Kokic et al. (2022) as well as a research article by Hasan et al. (2022) are selected to answer the research question. AMSTAR2 and the PEDro scale were used to assess their methodological quality and risk of bias. Results: 20% of the studies included in this paper measured significant results for the parameter functionality of the knee joint. 50 % of the studies provide clinically relevant results for quadriceps strength, which support the use of EMGBF. 20% of the studies show significance in the improvement of ROM and 30% in pain relief in the intervention group compared to the control group. Conclusion: The author of this paper concludes from the results that EMGBF can be a useful addition to quadriceps femoris strengthening in rehabilitation. For the remaining three parameters ROM, pain and functionality of the knee joint, the evidence of clinical relevance is lower. Therefore, the availability, cost-effectiveness and the preferences of therapist and patient should be considered to decide whether to use EMGBF or not

Dynamic light scattering from single macroscopic particles

Here we present a methodology to characterize the light intensity fluctuations that arise from rotations of individual granular particles. We describe a setup for dynamic light scattering measurements on individual macroscopic particles and isolate the contribution from rotations of the individual particles to the obtained correlation functions. The results show that rotation of granular particles results in a significant contribution to scattered light intensity fluctuations, a phenomenon not considered so far in dynamic light scattering measurements on fluidized granular media. The results presented here may thus form the basis for an extended light scattering methodology for granular media, and improve the selection of granular particles according to their dynamic light scattering signal. (C) 2021 Optical Society of Americ