Validierung und psychometrische Eigenschaften der deutschen Version des SWAL-QOL – Ein Fragebogen zur Lebensqualität von Menschen mit Schluckstörungen

Der SWAL-QOL ist ein weitläufig genutztes Instrument zur Messung der schluckbezogenen Lebensqualität mit vergleichsweise herausragenden psychometrischen Eigenschaften. Eine interkulturell adaptierte und validierte deutsche Version war bisher nicht verfügbar. Ziel dieser Studie war es, den SWAL-QOL nach international anerkannten Richtlinien zu übersetzen und die psychometrischen Eigenschaften der neuen deutschen Version systematisch aufzuzeigen. Der englische SWAL-QOL wurde nach den Richtlinien von Sousa und Rojjanasrirat übersetzt, kulturell adaptiert und auf Verständlichkeit getestet (1. Durchlauf n = 45 Patienten mit Dysphagie, 2. Durchlauf n = 22 Patienten mit Dysphagie). Daraufhin wurden die psychometrischen Eigenschaften der neuen deutschen SWAL-QOL-Version (G-SWAL-QOL) anhand von 103 Patienten mit Dysphagie und 55 gesunden Kontrollen untersucht. Für die Einschätzung der Konstruktvalidität wurde (i) eine Hauptkomponentenanalyse zur Dimensionalitätserfassung durchgeführt, (ii) die konvergente und die diskriminante Validität mithilfe des M. D. Anderson Dysphagia Inventory (MDADI-D) und des Short Form 36 (SF 36) abgeleitet und (iii) die Diskriminierungsfähigkeit des Fragebogens durch Gruppenvergleiche untersucht. Weiterhin wurde die Kriteriumsvalidität durch Korrelationen mit der Symptomstärke eingeschätzt. Um die Reliabilität des G-SWAL-QOL zu beurteilen, wurden die interne Konsistenz und die Retest-Reliabilität (n = 20 Patienten mit Dysphagie) untersucht. Alle Items des G-SWAL-QOL waren verständlich, mit Ausnahme eines Items (Item #29), welches daraufhin überarbeitet wurde. In der Hauptkomponentenanalyse konnten drei dem G-SWAL-QOL unterliegende Konstrukte extrahiert werden: schluckbezogene Lebensqualität, allgemeine gesundheitsbezogene Lebensqualität und kommunikationsbezogene Lebensqualität. Weiterhin konnte konvergente Validität durch moderate bis hohe Korrelationen mit dem MDADI-D (Rangkorrelation nach Spearman [rs] 0.36 – 0.88) und durch schwache bis moderate Korrelationen der eher allgemein gehaltenen G-SWAL-QOL-Subskalen mit dem SF-36 (rs 0.34 – 0.63) abgeleitet werden. Diskriminante Validität konnte durch die Abwesenheit von Korrelationen sehr dysphagiespezifischer G-SWAL-QOL-Subskalen mit dem SF-36 abgeleitet werden. Der G SWAL-QOL konnte zwischen der Patientengruppe und der gesunden Kontrollgruppe unterscheiden (p 0.7 für alle Subskalen mit Ausnahme der Subskala Eating Desire [α = 0.69]) und Retest-Reliabilität (rs ≥ 0.68 für alle Subskalen; Intraklassen-Korrelation ≥ 0.81 für alle Subskalen) aufgezeigt werden. Zusammenfassend stellt der G-SWAL-QOL ein umfassendes Messinstrument mit soliden psychometrischen Eigenschaften zur Erfassung der schluckbezogenen Lebensqualität im deutschsprachigen Raum dar. Allerdings ist er nicht für Patienten geeignet, die sich ausschließlich per Nahrungssonde ernähren. Hier besteht der Bedarf einer modifizierten Version speziell für Patienten ohne orale Nahrungsaufnahme

Effects of an education program on knowledge and self-perception of school personnel in preparing to care for type 1 diabetes students

Avaliar a formação acadêmica e profissional dos educadores escolares; avaliar o impacto do Diabetes + Apoio dado pelo Programa Responsáveis Escolares pelas Crianças com Diabetes Tipo 1 no nível de conhecimento e de confiança dos educadores escolares, para apoiar os alunos com diabetes tipo 1; comparar o nível de conhecimento dos educadores escolares com suas variáveis acadêmicas e profissionais.info:eu-repo/semantics/publishedVersio

Hybrid bioactive hydrogels containing single-walled carbon nanotubes covalently integrated via strain-promoted azide-alkyne cycloaddition

A non-photochemical and metal-free orthogonal route for the covalent incorporation of single-walled carbon nanotubes into a κ-carrageenan-based bioactive hydrogel scaffold is reported. The characterization of materials was carried out by usual analytical techniques and hybrid biohydrogels were evaluated for in vitro cytotoxicity on HeLa cell lines. The results revealed a significant antiproliferative effect instead of additional cytotoxicity with respect to native hydrogels.Peer reviewe

Prognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome

Objective: To assess the prognostic value of MOG antibodies (abs) in the differential diagnosis of acquired demyelinating syndromes (ADS). Methods: Clinical course, MRI, MOG-abs, AQP4-abs, and CSF cells and oligoclonal bands (OCB) in children with ADS and 24 months of follow-up were reviewed in this observational prospective multicenter hospital-based study. Results: Two hundred ten children with ADS were included and diagnosed with acute disseminated encephalomyelitis (ADEM) (n = 60), neuromyelitis optica spectrum disorder (NMOSD) (n = 12), clinically isolated syndrome (CIS) (n = 101), and multiple sclerosis (MS) (n = 37) after the first episode. MOG-abs were predominantly found in ADEM (57%) and less frequently in NMOSD (25%), CIS (25%), or MS (8%). Increased MOG-ab titers were associated with younger age (p = 0.0001), diagnosis of ADEM (p = 0.005), increased CSF cell counts (p = 0.011), and negative OCB (p = 0.012). At 24-month follow-up, 96 children had no further relapses. Thirtyfive children developed recurrent non-MS episodes (63% MOG-, 17% AQP4-abs at onset). Seventy-nine children developed MS (4% MOG-abs at onset). Recurrent non-MS episodes were associated with high MOG-ab titers (p = 0.0003) and older age at onset (p = 0.024). MS was predicted by MS-like MRI (p = 1:1,280 predicted a non-MS course with a sensitivity of 47% and a specificity of 100% and a recurrent non-MS course with a sensitivity of 46% and a specificity of 86%. Conclusions: Our results show that the presence of MOG-abs strongly depends on the age at disease onset and that high MOG-ab titers were associated with a recurrent non-MS disease course

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival