The inflamed patients exhibited higher serum irisin concentrations (median 6.77 ng/ml; 95% CI for the median 5.97-7.23) than those observed in the ABCD cohort (median 5.21 ng/ml; 95% CI for the median 5.08-5.30; p less then 0.001). Irisin concentrations were significantly correlated with age (r=-0.44; p less then 0.001), creatinine (r=-0.35; p less then 0.05), and fibrinogen (r=0.40; p less then 0.05) concentrations. No association was observed between irisin, interleukine-6 and tumor necrosis factor alpha. This study confirms the association between inflammation and irisin concentrations. Further studies are needed to understand the mechanisms underlying this association and its possible clinical implications. © Georg Thieme Verlag KG Stuttgart · New York.BACKGROUND  Modeling human cardiac diseases with induced pluripotent stem cells not only enables to study disease pathophysiology and develop therapies but also, as we have previously showed, it can offer a tool for disease diagnostics. We previously observed that a few genetic cardiac diseases can be separated from each other and healthy controls by applying machine learning to Ca2+ transient signals measured from iPSC-derived cardiomyocytes (CMs). OBJECTIVES  For the current research, 419 hypertrophic cardiomyopathy (HCM) transient signals and 228 long QT syndrome (LQTS) transient signals were measured. HCM signals included data recorded from iPSC-CMs carrying either α-tropomyosin, i.e., TPM1 (HCMT) or MYBPC3 or myosin-binding protein C (HCMM) mutation and LQTS signals included data recorded from iPSC-CMs carrying potassium voltage-gated channel subfamily Q member 1 (KCNQ1) mutation (long QT syndrome 1 [LQT1]) or KCNH2 mutation (long QT syndrome 2 [LQT2]). The main objective was to study whether and how effectively HCMM and HCMT can be separated from each other as well as LQT1 from LQT2.  https://www.selleckchem.com/products/AZD2281(Olaparib).html  METHODS  After preprocessing those Ca2+ signals where we computed peak waveforms we then classified the two mutations of both disease pairs by using several different machine learning methods. RESULTS  We obtained excellent classification accuracies of 89% for HCM and even 100% for LQT at their best. CONCLUSION  The results indicate that the methods applied would be efficient for the identification of these genetic cardiac diseases. Georg Thieme Verlag KG Stuttgart · New York.in English, German HINTERGRUND  Bei Rezidiv-Plattenepithelkarzinom des Hypopharynx/Larynx nach Bestrahlung stellt die Salvage-Laryngektomie (Salvage-LE) die beste kurative Therapieoption dar. Vorbestrahlung begünstigt die Entstehung pharyngokutaner Fisteln (pk-Fisteln). Transfer von unbestrahltem Gewebe in das OP-Gebiet reduziert die Fistelrate. Hierfür wird oft ein myokutaner Pectoralis-major-Lappen (PML) verwendet. Wir beschreiben einen muskelsparenden, myofaszialen PML (ms-PML) und dessen funktionellen und ästhetischen Resultate. METHODEN  Über je eine 8 cm lange subklavikuläre und submammäre horizontale Inzision wird ein am R. pectoralis der A. thoracoacromialis gestielter kraniokaudaler Streifen des M. pectoralis major unter Schonung der Pars clavicularis präpariert und supraklavikulär auf den Pharynx aufgebracht. R0-Resektionsraten, Gesamtüberleben (GS), Komplikationen, stationäre Verweildauern und funktionelle und ästhetische Resultat wurden erhoben. ERGEBNISSE  Bei 25 Patienten wurde eine Salvage-LE mit ms-PML durchgeführt. Die R0-Resektionsrate betrug 100 %, das mediane GS 1,3 (Beobachtungszeitraum 2,8) Jahre, die Komplikationsrate 16 % (4 komplette Lappennekrosen, 3 pk-Fisteln) und die mediane stationäre Verweildauer 20 (11–78) Tage. Gute funktionelle Ergebnisse wurden beobachtet Einschränkungen der oralen Nahrungsaufnahme traten bei 2, Einschränkungen der Stimmrehabilitation bei 3 Patienten auf. Wundheilungsstörungen ohne Lappennekrosen wurden nicht beobachtet. Die ästhetischen Resultate waren ansprechend. SCHLUSSFOLGERUNG  Der ms-PML ist ein wenig invasives und sicheres Verfahren zur Fistelprophylaxe bei Salvage-LE mit günstigem funktionellem und ästhetischem Ergebnis.Drug-evoked adaptations in the mesolimbic dopamine system are postulated to drive opioid abuse and addiction. These adaptations vary in magnitude and direction following different patterns of opioid exposure, but few studies have systematically manipulated the pattern of opioid administration while measuring neurobiological and behavioral impact. We exposed male and female mice to morphine for one week, with administration patterns that were either intermittent (daily injections) or continuous (osmotic minipump infusion). We then interrupted continuous morphine exposure with either naloxone-precipitated or spontaneous withdrawal. Continuous morphine exposure caused tolerance to the psychomotor-activating effects of morphine, whereas both intermittent and interrupted morphine exposure caused long-lasting psychomotor sensitization. Given links between locomotor sensitization and mesolimbic dopamine signaling, we used fiber photometry and a genetically encoded dopamine sensor to conduct longitudinal measurements of dopamine dynamics in the nucleus accumbens. Locomotor sensitization caused by interrupted morphine exposure was accompanied by enhanced dopamine signaling in the nucleus accumbens. To further assess downstream consequences on striatal gene expression, we used next-generation RNA sequencing to perform genome-wide transcriptional profiling in the nucleus accumbens and dorsal striatum. The interruption of continuous morphine exposure exacerbated drug-evoked transcriptional changes in both nucleus accumbens and dorsal striatum, dramatically increasing differential gene expression and engaging unique signaling pathways. Our study indicates that opioid-evoked adaptations in brain function and behavior are critically dependent on the pattern of drug administration, and exacerbated by interruption of continuous exposure. Maintaining continuity of chronic opioid administration may, therefore, represent a strategy to minimize iatrogenic effects on brain reward circuits.BACKGROUND Optics can be used for guidance in deep brain stimulation (DBS) surgery. The aim was to use laser Doppler flowmetry (LDF) to investigate the intraoperative optical trajectory along the ventral intermediate nucleus (VIM) and zona incerta (Zi) regions in patients with essential tremor during asleep DBS surgery, and whether the Zi region could be identified. METHODS A forward-looking LDF guide was used for creation of the trajectory for the DBS lead, and the microcirculation and tissue greyness, i.e., total light intensity (TLI) was measured along 13 trajectories. TLI trajectories and the number of high-perfusion spots were investigated at 0.5-mm resolution in the last 25 mm from the targets. RESULTS All implantations were done without complications and with significant improvement of tremor (p less then 0.01). Out of 798 measurements, 12 tissue spots showed high blood flow. The blood flow was significantly higher in VIM than in Zi (p less then 0.001). The normalized mean TLI curve showed a significant (p less then 0.