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  • 1
    Online-Ressource
    Online-Ressource
    Oxford University Press (OUP) ; 2019
    In:  Microscopy and Microanalysis Vol. 25, No. S2 ( 2019-08), p. 544-545
    In: Microscopy and Microanalysis, Oxford University Press (OUP), Vol. 25, No. S2 ( 2019-08), p. 544-545
    Materialart: Online-Ressource
    ISSN: 1431-9276 , 1435-8115
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2019
    ZDB Id: 1481716-0
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: Brain, Oxford University Press (OUP), Vol. 146, No. 2 ( 2023-02-13), p. 600-611
    Kurzfassung: Anti-IgLON5 disease is a newly defined clinical entity characterized by a progressive course with high disability and mortality rate. While precise pathogenetic mechanisms remain unclear, features characteristic of both autoimmune and neurodegenerative diseases were reported. Data on immunotherapy are limited, and its efficacy remains controversial. In this study, we retrospectively investigated an anti-IgLON5 disease cohort with special focus on clinical, serological and genetic predictors of the immunotherapy response and long-term outcome. Patients were recruited from the GENERATE (German Network for Research on Autoimmune Encephalitis) registry. Along with clinical parameters, anti-IgLON5 immunoglobulin (Ig)G in serum and CSF, anti-IgLON5 IgG1-4, IgA and IgM in serum, neurofilament light chain and glial fibrillary acidic protein in serum as well as human leukocyte antigen-genotypes were determined. We identified 53 patients (symptom onset 63.8 ± 10.3 years, female:male 1:1.5). The most frequent initial clinical presentations were bulbar syndrome, hyperkinetic syndrome or isolated sleep disorder [at least one symptom present in 38% (20/53)]. At the time of diagnosis, the majority of patients had a generalized multi-systemic phenotype; nevertheless, 21% (11/53) still had an isolated brainstem syndrome and/ or a characteristic sleep disorder only. About one third of patients [28% (15/53)] reported subacute disease onset and 51% (27/53) relapse-like exacerbations during the disease course. Inflammatory CSF changes were evident in 37% (19/51) and increased blood-CSF-barrier permeability in 46% (21/46). CSF cell count significantly decreased, while serum anti-IgLON5 IgG titre increased with disease duration. The presence of human leukocyte antigen-DRB1*10:01 [55% (24/44)] was associated with higher serum anti-IgLON5 IgG titres. Neurofilament light chain and glial fibrillary acidic protein in serum were substantially increased (71.1 ± 103.9 pg/ml and 126.7 ± 73.3 pg/ml, respectively). First-line immunotherapy of relapse-like acute-to-subacute exacerbation episodes resulted in improvement in 41% (11/27) of patients and early initiation within the first 6 weeks was a predictor for therapy response. Sixty-eight per cent (36/53) of patients were treated with long-term immunotherapy and 75% (27/36) of these experienced no further disease progression (observation period of 20.2 ± 15.4 months). Long-term immunotherapy initiation during the first year after onset and low pre-treatment neurofilament light chain were significant predictors for a better outcome. In conclusion, subacute disease onset and early inflammatory CSF changes support the primary role of autoimmune mechanisms at least at initial stages of anti-IgLON5 disease. Early immunotherapy, prior to advanced neurodegeneration, is associated with a better long-term clinical outcome. Low serum neurofilament light chain at treatment initiation may serve as a potential biomarker of the immunotherapy response.
    Materialart: Online-Ressource
    ISSN: 0006-8950 , 1460-2156
    RVK:
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2023
    ZDB Id: 1474117-9
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: Archives of Toxicology, Springer Science and Business Media LLC, Vol. 93, No. 12 ( 2019-12), p. 3503-3521
    Kurzfassung: Aluminium is one of the most abundant elements in earth’s crust and its manifold uses result in an exposure of the population from many sources. Developmental toxicity, effects on the urinary tract and neurotoxicity are known effects of aluminium and its compounds. Here, we assessed the health risks resulting from total consumer exposure towards aluminium and various aluminium compounds, including contributions from foodstuffs, food additives, food contact materials (FCM), and cosmetic products. For the estimation of aluminium contents in foodstuff, data from the German “Pilot-Total-Diet-Study” were used, which was conducted as part of the European TDS-Exposure project. These were combined with consumption data from the German National Consumption Survey II to yield aluminium exposure via food for adults. It was found that the average weekly aluminium exposure resulting from food intake amounts to approx. 50% of the tolerable weekly intake (TWI) of 1 mg/kg body weight (bw)/week, derived by the European Food Safety Authority (EFSA). For children, data from the French “Infant Total Diet Study” and the “Second French Total Diet Study” were used to estimate aluminium exposure via food. As a result, the TWI can be exhausted or slightly exceeded—particularly for infants who are not exclusively breastfed and young children relying on specially adapted diets (e.g. soy-based, lactose free, hypoallergenic). When taking into account the overall aluminium exposure from foods, cosmetic products (cosmetics), pharmaceuticals and FCM from uncoated aluminium, a significant exceedance of the EFSA-derived TWI and even the PTWI of 2 mg/kg bw/week, derived by the Joint FAO/WHO Expert Committee on Food Additives, may occur. Specifically, high exposure levels were found for adolescents aged 11–14 years. Although exposure data were collected with special regard to the German population, it is also representative for European and comparable to international consumers. From a toxicological point of view, regular exceedance of the lifetime tolerable aluminium intake (TWI/PTWI) is undesirable, since this results in an increased risk for health impairments. Consequently, recommendations on how to reduce overall aluminium exposure are given.
    Materialart: Online-Ressource
    ISSN: 0340-5761 , 1432-0738
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2019
    ZDB Id: 1458459-1
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: Brain, Oxford University Press (OUP), Vol. 146, No. 3 ( 2023-03-01), p. 977-990
    Kurzfassung: Autoimmune neurological syndromes (AINS) with autoantibodies against the 65 kDa isoform of the glutamic acid decarboxylase (GAD65) present with limbic encephalitis, including temporal lobe seizures or epilepsy, cerebellitis with ataxia, and stiff-person-syndrome or overlap forms. Anti-GAD65 autoantibodies are also detected in autoimmune diabetes mellitus, which has a strong genetic susceptibility conferred by human leukocyte antigen (HLA) and non-HLA genomic regions. We investigated the genetic predisposition in patients with anti-GAD65 AINS. We performed a genome-wide association study (GWAS) and an association analysis of the HLA region in a large German cohort of 1214 individuals. These included 167 patients with anti-GAD65 AINS, recruited by the German Network for Research on Autoimmune Encephalitis (GENERATE), and 1047 individuals without neurological or endocrine disease as population-based controls. Predictions of protein expression changes based on GWAS findings were further explored and validated in the CSF proteome of a virtually independent cohort of 10 patients with GAD65-AINS and 10 controls. Our GWAS identified 16 genome-wide significant (P & lt; 5 × 10−8) loci for the susceptibility to anti-GAD65 AINS. The top variant, rs2535288 [P = 4.42 × 10−16, odds ratio (OR) = 0.26, 95% confidence interval (CI) = 0.187–0.358], localized to an intergenic segment in the middle of the HLA class I region. The great majority of variants in these loci ( & gt;90%) mapped to non-coding regions of the genome. Over 40% of the variants have known regulatory functions on the expression of 48 genes in disease relevant cells and tissues, mainly CD4+ T cells and the cerebral cortex. The annotation of epigenomic marks suggested specificity for neural and immune cells. A network analysis of the implicated protein-coding genes highlighted the role of protein kinase C beta (PRKCB) and identified an enrichment of numerous biological pathways participating in immunity and neural function. Analysis of the classical HLA alleles and haplotypes showed no genome-wide significant associations. The strongest associations were found for the DQA1*03:01-DQB1*03:02-DRB1*04:01HLA haplotype (P = 4.39 × 10−4, OR = 2.5, 95%CI = 1.499–4.157) and DRB1*04:01 allele (P = 8.3 × 10−5, OR = 2.4, 95%CI = 1.548–3.682) identified in our cohort. As predicted, the CSF proteome showed differential levels of five proteins (HLA-A/B, C4A, ATG4D and NEO1) of expression quantitative trait loci genes from our GWAS in the CSF proteome of anti-GAD65 AINS. These findings suggest a strong genetic predisposition with direct functional implications for immunity and neural function in anti-GAD65 AINS, mainly conferred by genomic regions outside the classical HLA alleles.
    Materialart: Online-Ressource
    ISSN: 0006-8950 , 1460-2156
    RVK:
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2023
    ZDB Id: 1474117-9
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    Online-Ressource
    Online-Ressource
    Cambridge University Press (CUP) ; 2004
    In:  Infection Control & Hospital Epidemiology Vol. 25, No. 11 ( 2004-11), p. 897-899
    In: Infection Control & Hospital Epidemiology, Cambridge University Press (CUP), Vol. 25, No. 11 ( 2004-11), p. 897-899
    Materialart: Online-Ressource
    ISSN: 0899-823X , 1559-6834
    Sprache: Englisch
    Verlag: Cambridge University Press (CUP)
    Publikationsdatum: 2004
    ZDB Id: 2106319-9
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    Online-Ressource
    Online-Ressource
    Massachusetts Medical Society ; 2005
    In:  New England Journal of Medicine Vol. 353, No. 5 ( 2005-08-04), p. 532-533
    In: New England Journal of Medicine, Massachusetts Medical Society, Vol. 353, No. 5 ( 2005-08-04), p. 532-533
    Materialart: Online-Ressource
    ISSN: 0028-4793 , 1533-4406
    RVK:
    Sprache: Englisch
    Verlag: Massachusetts Medical Society
    Publikationsdatum: 2005
    ZDB Id: 1468837-2
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    Online-Ressource
    Online-Ressource
    Cambridge University Press (CUP) ; 2005
    In:  Infection Control & Hospital Epidemiology Vol. 26, No. 8 ( 2005-08), p. 703-707
    In: Infection Control & Hospital Epidemiology, Cambridge University Press (CUP), Vol. 26, No. 8 ( 2005-08), p. 703-707
    Kurzfassung: To determine the efficacy and tolerability of octenidine hydrochloride, a non-alcoholic skin antiseptic, for the care of central venous catheter (CVC) insertion sites. Design: Prospective, observational study. Setting: Bone marrow transplantation unit of a university hospital. Patients: All consecutive patients with a nontunneled CVC were enrolled prospectively after informed consent. Methods: Octenidine hydrochloride (0.1%) was applied for disinfection at the CVC insertion site during dressing changes. The following cultures were performed weekly as well as at the occurrence of any systemic inflammatory response syndrome criteria: cultures of the skin surrounding the CVC entry site, cultures of the three-way hub connected to the CVC, blood cultures, and cultures of the CVC tip on removal. Enhanced microbiological methods (skin swabs of a 24-cm2 standardized area, roll plate, and sonication of catheter tips) were applied. Results: One hundred thirty-five CVCs were inserted in 62 patients during the study period and remained for a mean period of 19.1 days, corresponding to 2,462 catheter-days. Bacterial density at the insertion site declined substantially over time, and most cultures became negative 2 weeks after insertion. Only 6 patients had a documented catheter-related bloodstream infection. The incidence density was 2.39 catheter infections per 1,000 catheter-days. No side effects were noted with application of the antiseptic. Conclusions: Disinfection with a skin antiseptic that contains octenidine hydrochloride is highly active and well tolerated. It leads to a decrease in skin colonization over time and may be a new option for CVC care.
    Materialart: Online-Ressource
    ISSN: 0899-823X , 1559-6834
    Sprache: Englisch
    Verlag: Cambridge University Press (CUP)
    Publikationsdatum: 2005
    ZDB Id: 2106319-9
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    Online-Ressource
    Online-Ressource
    Oxford University Press (OUP) ; 2019
    In:  Annals of Botany Vol. 124, No. 6 ( 2019-11-27), p. 891-901
    In: Annals of Botany, Oxford University Press (OUP), Vol. 124, No. 6 ( 2019-11-27), p. 891-901
    Kurzfassung: In oilseed rape (Brassica napus) semi-dwarf hybrid varieties from crosses between bzh dwarf and normal-type lines are of increasing interest. They have improved nitrogen (N) uptake, N-utilization and N-use efficiency compared to normal types. This study aimed to elucidate whether these N-related effects can be explained by the bzh shoot growth-type alone or also by differences in root traits. Methods Root system size was measured using root electrical capacitance (EC) in field trials with two N levels in two sets of genotypes segregating for the bzh-locus: (1) 108 doubled haploid (DH) test hybrids in two seasons, 2010–2012, and (2) 16 near-isogenic hybrids in the 2016–17 season. Quantitative trait loci (QTL) for root EC were estimated in DH test hybrids. Seedling root architecture parameters were monitored in vitro. Key Results In vitro root growth showed a higher root: shoot ratio in bzh semi-dwarf hybrids. Root EC in field trials was higher at high N supply than at zero N fertilization. In most trials semi-dwarf hybrids had higher EC than normal-type hybrids, but they reduced root EC in response to N limitation more than normal types. Root EC was more heritable at the end of flowering (h2 = 0.73) than at the beginning of flowering (h2 = 0.36) in near-isogenic hybrids and had a lower heritability in trials of DH test hybrids (h2 = 0.27). A QTL for root EC in the genomic region of the bzh-locus on linkage group A06 was significant at zero N fertilization. Conclusions Root EC proved to be a meaningful method in oilseed rape breeding programmes targeting root system size. The greater reduction of semi-dwarf root EC compared to the normal type under low N supply with simultaneous increase in N efficiency implies that in roots it is not a question of ‘the more the merrier’ and that the bzh root system reacts highly economically when N is scarce.
    Materialart: Online-Ressource
    ISSN: 0305-7364 , 1095-8290
    RVK:
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2019
    ZDB Id: 1461328-1
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    Online-Ressource
    Online-Ressource
    Elsevier BV ; 1983
    In:  Tetrahedron Letters Vol. 24, No. 34 ( 1983-1), p. 3579-3582
    In: Tetrahedron Letters, Elsevier BV, Vol. 24, No. 34 ( 1983-1), p. 3579-3582
    Materialart: Online-Ressource
    ISSN: 0040-4039
    RVK:
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 1983
    ZDB Id: 2007074-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    In: Gastroenterology, Elsevier BV, Vol. 139, No. 5 ( 2010-11), p. 1593-1601
    Materialart: Online-Ressource
    ISSN: 0016-5085
    RVK:
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2010
    Standort Signatur Einschränkungen Verfügbarkeit
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