12 research outputs found
Initial Genomics of the Human Nucleolus
We report for the first time the genomics of a nuclear compartment of the eukaryotic cell. 454 sequencing and microarray analysis revealed the pattern of nucleolus-associated chromatin domains (NADs) in the linear human genome and identified different gene families and certain satellite repeats as the major building blocks of NADs, which constitute about 4% of the genome. Bioinformatic evaluation showed that NADâlocalized genes take part in specific biological processes, like the response to other organisms, odor perception, and tissue development. 3D FISH and immunofluorescence experiments illustrated the spatial distribution of NADâspecific chromatin within interphase nuclei and its alteration upon transcriptional changes. Altogether, our findings describe the nature of DNA sequences associated with the human nucleolus and provide insights into the function of the nucleolus in genome organization and establishment of nuclear architecture
Effectiveness and safety of opicapone in Parkinsonâs disease patients with motor fluctuations: the OPTIPARK open-label study
Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinsonâs disease and motor fluctuations were treated with opicapone 50âmg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinicianâs Global Impression of Change (CGI-C) after 3âmonths. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinsonâs Disease Rating Scale (UPDRS), Parkinsonâs Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3âmonths of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3âmonths, respectively (full analysis set). At 6âmonths, for UK subgroup only (nâ=â95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3âmonths showed statistically significant improvements in activities of daily living during OFF (meanâ±âSD change from baseline: ââ3.0â±â4.6, pâ<â0.0001) and motor scores during ON (ââ4.6â±â8.1, pâ<â0.0001). The meanâ±âSD improvements of ââ3.4â±â12.8 points for PDQ-8 and -6.8â±â19.7 points for NMSS were statistically significant versus baseline (both pâ<â0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Conclusions Opicapone 50âmg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Trial registration Registered in July 2016 at clinicaltrials.gov (NCT02847442)
Schemaanalyse und Funktionsanalyse in der Verhaltensdiagnostik: Eine empirische Studie zu Ăberlebensregel und Reaktionskette zum Symptom
Bei den Patienten einer Therapiestudie wurde eine Schemaanalyse zur Identifizierung der impliziten dysfunktionalen Ăberlebensregel durchgefĂŒhrt, die inhaltsanalytisch untersucht wurde. Zudem wurde mit einer Funktionsanalyse die individuelle Reaktionskette bis zur Symptombildung erarbeitet und diese ebenfalls inhaltsanalytisch untersucht. Die Verbindung von Schema- und Funktionsanalyse zu einem individuellen Störungsmodell ergab einen hohen ErklĂ€rungswert. Die Reaktionskette wird wesentlich durch die Ăberlebensregel gesteuert. Der primĂ€re Handlungsimpuls in der symptomauslösenden Situation verstöĂt gegen die individuelle Ăberlebensregel, wird unterdrĂŒckt, und stattdessen erfolgt eine Handlung, die die Ăberlebensregel erlaubt. Die gezielte therapeutische Ănderung der Ăberlebensregel und ihres Einflusses auf Erleben und Verhalten war möglich. Es liegen sehr gute EffektstĂ€rken vor