250 episodios

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Medizin - Open Access LMU - Teil 19/22 Ludwig-Maximilians-Universität München

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Die Universitätsbibliothek (UB) verfügt über ein umfangreiches Archiv an elektronischen Medien, das von Volltextsammlungen über Zeitungsarchive, Wörterbücher und Enzyklopädien bis hin zu ausführlichen Bibliographien und mehr als 1000 Datenbanken reicht. Auf iTunes U stellt die UB unter anderem eine Auswahl an elektronischen Publikationen der Wissenschaftlerinnen und Wissenschaftler an der LMU bereit. (Dies ist der 19. von 22 Teilen der Sammlung 'Medizin - Open Access LMU'.)

    Impact of histone H4 lysine 20 methylation on 53BP1 responses to chromosomal double strand breaks.

    Impact of histone H4 lysine 20 methylation on 53BP1 responses to chromosomal double strand breaks.

    Recruitment of 53BP1 to chromatin flanking double strand breaks (DSBs) requires γH2AX/MDC1/RNF8-dependent ubiquitination of chromatin and interaction of 53BP1 with histone H4 methylated on lysine 20 (H4K20me). Several histone methyltransferases have been implicated in 53BP1 recruitment, but their quantitative contributions to the 53BP1 response are unclear. We have developed a multi-photon laser (MPL) system to target DSBs to subfemtoliter nuclear volumes and used this to mathematically model DSB response kinetics of MDC1 and of 53BP1. In contrast to MDC1, which revealed first order kinetics, the 53BP1 MPL-DSB response is best fitted by a Gompertz growth function. The 53BP1 MPL response shows the expected dependency on MDC1 and RNF8. We determined the impact of altered H4K20 methylation on 53BP1 MPL response kinetics in mouse embryonic fibroblasts (MEFs) lacking key H4K20 histone methyltransferases. This revealed no major requirement for the known H4K20 dimethylases Suv4-20h1 and Suv4-20h2 in 53BP1 recruitment or DSB repair function, but a key role for the H4K20 monomethylase, PR-SET7. The histone methyltransferase MMSET/WHSC1 has recently been implicated in 53BP1 DSB recruitment. We found that WHSC1 homozygous mutant MEFs reveal an alteration in balance of H4K20 methylation patterns; however, 53BP1 DSB responses in these cells appear normal.

    Antidepressant drugs and the response in the placebo group: the real problem lies in our understanding of the issue

    Antidepressant drugs and the response in the placebo group: the real problem lies in our understanding of the issue

    In a recent paper, Horder and colleagues (Horder et al., 2010, J Psychopharmacol 25: 1277–1288) have suggested that the mainproblem in the Kirsch analysis is methodological. We argue that the results are similar irrespective of the method used. In our opinion the data suggest that placebo and drug effects are non-additive: antidepressants act independently of depression severity, while the placebo effect is present only in milder cases. While the response in the placebo group is due to unstable ‘noise’ and ‘artefacts’, the medication effect is reliable, valid and stable.

    Self-reported muscle pain in adolescents with migraine and tension-type headache

    Self-reported muscle pain in adolescents with migraine and tension-type headache

    Aim: To identify possible associations between muscular pain and headache in adolescents in a large population-based sample.
    Methods: Grammar school students were invited to fill in a questionnaire on headache and associated lifestyle factors. Headache was classified according to the German version of the International Classification of Headache Disorders (2nd edition). Muscular pain was assessed via denoting affected areas in schematic drawings of a body and via provoked muscular pain on controlled movements of head, neck and shoulder regions.
    Results: Prevalence of any headache within the previous 6 months exceeded 80%. In all subjects muscular pain or pain on movement was most prominent in the neck and shoulder region, ranging from 9% to 27% in the non-headache population to up to 63% for individuals with migraine or mixed migraine and tension-type headache (TTH). Frequency of muscular pain increased significantly with growing chronicity of TTH.
    Interpretation: A strong association between muscle pain in the neck/shoulder region and headache was observed, pointing to the importance of muscular pain for headache in adolescents. Also, in this age group muscular pain appears to be of particular importance in chronic TTH and – unexpectedly – in migraine, which is the most important new finding in our study.

    Fibromyalgia Syndrome and Chronotype: Late Chronotypes Are More Affected

    Fibromyalgia Syndrome and Chronotype: Late Chronotypes Are More Affected

    Sleep has strong links to the symptomology of fibromyalgia syndrome (FMS), a diffuse musculoskeletal pain disorder. Information about the involvement of the circadian clock is, however, sparse. In this study, 1548 individuals with FMS completed an online survey containing questions on demographics, stimulant consumption, sleep quality, well-being and subjective pain, chronotype (assessed by the Munich ChronoType Questionnaire, MCTQ), and FMS impact. Chronotype (expressed as the mid-sleep-point on free days, corrected for sleep deficit on workdays, MSFsc) significantly correlated with stress-ratings, so-called “memory failures in everyday life,” fatigue, FMS impact, and depression but not with anxiety. When chronotypes were categorized into 3 groups (early, intermediate, late), significant group differences were found for sum scores of perceived stress, memory failures in everyday life, fatigue, FMS impact, and depression but not anxiety, with late chronotypes being more affected than early chronotypes. Sleepiness ratings were highest in early chronotypes. Challenges of sleep quality and subjective pain were significantly increased in both early and late chronotypes. The results show that according to their reports, late chronotypes are more affected by fibromyalgia.

    Glycoproteins as targets of autoantibodies in CNS inflammation: MOG and more

    Glycoproteins as targets of autoantibodies in CNS inflammation: MOG and more

    B cells and antibodies constitute an important element in different inflammatory diseases of the central nervous system (CNS). Autoantibodies can serve as a biomarker to identify disease subgroups and may in addition contribute to the pathogenic process. One candidate autoantigen for multiple sclerosis (MS) is myelin oligodendrocyte glycoprotein (MOG). MOG is localized at the outermost surface of myelin in the CNS and has been the focus of extensive research for more than 30 years. Its role as an important autoantigen for T cells and as a target of demyelinating autoantibodies has been established in several variants of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The literature regarding antibodies to MOG in MS patients is confusing and contradictory. Recent studies, however, have described high levels of antibodies to conformationally correct MOG in pediatric acquired demyelination, both acute disseminated encephalomyelitis (ADEM) and MS. In adult MS, such antibodies are rarely found and then only at low levels. In this review, we summarize key findings from animal models and patient studies, discuss challenges in detecting anti-MOG antibodies in patients and present recent approaches to identifying new autoantigens in MS.

    Whey- vs Casein-Based Enteral Formula and Gastrointestinal Function in Children With Cerebral Palsy.

    Whey- vs Casein-Based Enteral Formula and Gastrointestinal Function in Children With Cerebral Palsy.

    Objectives: Children with severe cerebral palsy (CP) commonly have gastrointestinal (GI) dysfunction. Whey-based enteral formulas have been postulated to reduce gastroesophageal reflux (GOR) and accelerate gastric emptying (GE). The authors investigated whether whey-based (vs casein-based) enteral formulas reduce GOR and accelerate GE in children who have severe CP with a gastrostomy and fundoplication.
    Methods: Thirteen children received a casein-based formula for 1 week and either a 50% whey whole protein (50% WWP) or a 100% whey partially hydrolyzed protein (100% WPHP) formula for 1 week. Reflux episodes, gastric half-emptying time (GE t1/2), and reported pain and GI symptoms were measured.
    Results: Whey formulas emptied significantly faster than casein (median [interquartile range (IQR)] GE t1/2, 33.9 [25.3-166.2] min vs 56.6 [46-191] min; P = .033). Reflux parameters were unchanged. GI symptoms were lower in children who received 50% WWP (visual analog symptom score, median [IQR], 0[0-11.8]) vs 100% WPHP (13.0 [2.5-24.8]) (P = .035).
    Conclusion: This pilot study shows that in children who have severe CP with a gastrostomy and fundoplication, GE of the whey-based enteral formula is significantly faster than casein. The acceleration in GE does not alter GOR frequency, and there appears to be no effect of whey vs casein in reducing acid, nonacid, and total reflux episodes. The results indicate that enteral formula selection may be particularly important for children with severe CP and delayed GE. (JPEN J Parenter Enteral Nutr. 2012;36:118S-123S)

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