The uptake of iodide into the thyroid, an essential step in thyroid hormone synthesis, is an active process mediated by the sodium-iodide symporter (NIS). Despite its strong dependence on TSH, the ...master regulator of the thyroid, the NIS gene was also reported to be regulated by non-TSH signaling pathways. In the present study we provide evidence that the rat NIS gene is subject to regulation by sterol regulatory element-binding proteins (SREBPs), which were initially identified as master transcriptional regulators of lipid biosynthesis and uptake. Studies in FRTL-5 thyrocytes revealed that TSH stimulates expression and maturation of SREBPs and expression of classical SREBP target genes involved in lipid biosynthesis and uptake. Almost identical effects were observed when the cAMP agonist forskolin was used instead of TSH. In TSH receptor-deficient mice, in which TSH/cAMP-dependent gene regulation is blocked, the expression of SREBP isoforms in the thyroid was markedly reduced when compared with wild-type mice. Sterol-mediated inhibition of SREBP maturation and/or RNA interference-mediated knockdown of SREBPs reduced expression of NIS and NIS-specific iodide uptake in FRTL-5 cells. Conversely, overexpression of active SREBPs caused a strong activation of the 5′-flanking region of the rat NIS gene mediated by binding to a functional SREBP binding site located in the 5′-untranslated region of the rat NIS gene. These findings show that TSH acts as a regulator of SREBP expression and maturation in thyroid epithelial cells and that SREBPs are novel transcriptional regulators of NIS.
We investigated whether physical load has an influence on the accuracy of duration estimation of sporting activities presented in real time and slow motion. 86 participants were studied in two single ...sessions of 45 min each.
Our results showed no general effects for physical load, when comparing physical load versus rest. However, we could replicate findings of past research (Schütz et al., 2021), showing that the duration of sports performance is estimated more accurately when presented in real time compared to slow motion. Further we found, that under physical load, participants perceiving the physical exercise as hard (RPE ≥15) estimated time significantly shorter and more accurately compared to participants perceiving the physical exercise as light or moderate (RPE <15).
Thus, our results suggest that using slow motion may worsen the assessment of sports performance. Additionally, we could show that intense physical exertion contributes to reducing the overestimation of time.
•High physical load influences duration estimation.•When physical exercise is perceived as hard time is estimated shorter and more accurately.•Intense physical exertion contributes to reducing the overestimation of time.
Nicotine may affect sleep by influencing sleep‐regulating neurotransmitters. Sleep disorders can increase the risk for depression and substance dependency. To detect the influence of sleep ...disturbances on the effect of smoking cessation, we investigated polysomnographically (PSG) the sleep of smoking subjects during a period of smoking, during withdrawal and after a period of abstinence from nicotine. Thirty‐three smokers (23 male, 10 female, median age 29 years, Fagerström Test for Nicotine Dependence score 6.3) were examined during smoking, 24–36 hours after smoking and 3 months after cessation. All subjects had an adaptation night followed by the PSG night. Compared with the smoking state, we found increased arousal index and wake time during nicotine withdrawal. Smokers who later relapsed (11) presented a higher degree of nicotine dependence and more withdrawal symptoms than those who abstained (22) and were characterized by less rapid eye movement (REM) sleep, a longer REM latency as well as by more intense sleep impairments in the subjective sleep rating during the withdrawal. Impairments of sleep during the withdrawal phase may reflect more severe nicotine dependence and may contribute to earlier relapse into smoking behaviours.
Zur Verbesserung der Diagnostik der Alzheimer-Erkrankung wird die klinische Testung zunehmend durch Biomarker ergänzt. Diese können sowohl mittels Hirnbildgebung als auch mittels Liquor-Analyse ...erhoben werden. Aufgrund der großen Bedeutung in der Pathogenese der Alzheimer-Erkrankung wurde das ß-Amyloid als diagnostisches Kriterium implementiert, ebenso wie die mediale Temporallappenatrophie. Bis zur Einführung der kombinierten PET/MRT konnten die Informationen zu den genannten Bildgebungsparametern nur separat mit Hilfe mehrerer Aufnahmen gewonnen werden. Ziel der Studie war es deshalb, erstmalig herauszufinden, ob mit Hilfe der kombinierten Amyloid-PET/MRT Biomarker-Informationen zu allen Kategorien erhoben werden können. Gleichzeitig sollte überprüft werden, ob diese neue Bildgebungsmethode mit einem höheren Komfort für die Patienten/deren Angehörige und für die Überweiser einhergeht.
Hierfür wurden die Daten der ersten 100 Probanden analysiert, die eine ß-Amyloid-Bildgebung am kombinierten PET/MRT in der nuklearmedizinischen Abteilung des Universitätsklinikums Leipzigs durchliefen. Es erfolgte eine visuelle und semiquantitative Analyse der Bildgebungsdaten sowie Umfragen bei den Patienten/deren Angehörigen und den überweisenden Ärzten. Anhand der Ergebnisse konnte gezeigt werden, dass die Methode in der Lage ist, Informationen zu allen Biomarkerkategorien bereitzustellen und dies mit einer hohen Patienten-/Angehörigen- bzw. Überweiser-Zufriedenheit einhergeht.:1. Alzheimer-Erkrankung
1.1 Epidemiologie
1.2 Klinische Präsentation
1.3 Pathologische Grundlagen
1.4 Diagnostik
1.4.1 Diagnostische Algorithmen
1.4.2 Biomarker
1.4.3 Bildgebende Verfahren
1.5 Therapie
2. Zielsetzung
In Australia, National Consumer Credit Protection (NCCP) and Consumer Credit Reporting (CCR) legislation have attempted to ensure better use of credit data in the financial services industry, and ...address the issues of willingness and capacity. However, the legislation has not solved the problems identified without unintended consequences. This paper examines the challenges involved in managing the market for credit data. It proposes a new approach to data access and usage and a regulatory mandate which combines aspects of prudential, consumer and privacy regulation. An earlier version of this paper was presented at the 21st Melbourne Money and Finance Conference.
Summary
Background
A single center phase Ib/II study of gemcitabine, nab-paclitaxel, and pembrolizumab (GNP) to evaluate the safety and efficacy in metastatic pancreatic adenocarcinoma (PDAC) was ...conducted (NCT02331251).
Methods
PDAC patients (pts) with measurable disease, biopsy proven metastasis, adequate laboratory tests, and KPS ≥ 70% received GNP until progression or toxicity. Safety monitoring, RECIST 1.1, and irRECIST assessments were conducted. Response imaging was performed prior to cycle 4, then every 3 months. Changes in tumor cell-free DNA copy number instability (CNI) was retrospectively evaluated.
Results
17 pts. with a median age of 56 were treated. 11 were women and all had a KPS of at least 80%. Grade 3 events occurred in 53% of patients. The phase II portion was completed for chemotherapy naïve PDAC pts. Of the 11 evaluable chemotherapy naïve PDAC, the disease control rate (partial response PR + stable diseaseSD) was 100%. There were 3 with PR on treatment for 8+, ~11, and 15 months; respectively. The primary endpoint of >15% complete response was not met. The median progression-free survival (PFS) and overall survival (OS) was 9.1 and 15.0 months for chemotherapy naïve treated patients. Of 9 patients evaluable for CNI change, a greater reduction in CNI correlated with longer PFS and improved OS.
Conclusions
GNP can be safely given to chemotherapy naïve PDAC patients. Efficacy appears to be slightly improved over previously reported results for standard weekly × 3 every 28 day gemcitabine and nab-paclitaxel dosing. CNI change may be prognostic for OS.
Previous research has shown that action effects of self-generated movements are internally predicted before outcome feedback becomes available. To test whether these sensorimotor predictions are used ...to facilitate visual information uptake for feedback processing, we measured eye movements during the execution of a goal-directed throwing task. Participants could fully observe the effects of their throwing actions (ball trajectory, and either hitting or missing a target) in most of the trials. In a portion of the trials, the ball trajectory was not visible, and participants only received static information about the outcome. We observed a large proportion of predictive saccades, shifting gaze toward the goal region before the ball arrived and outcome feedback became available. Fixation locations after predictive saccades systematically covaried with future ball positions in trials with continuous ball flight information, but notably also in trials with static outcome feedback and only efferent and proprioceptive information about the movement that could be used for predictions. Fixation durations at the chosen positions after feedback onset were modulated by action outcome (longer durations for misses than for hits) and outcome uncertainty (longer durations for narrow vs. clear outcomes). Combining both effects, durations were longest for narrow errors and shortest for clear hits, indicating that the chosen locations offer informational value for feedback processing. Thus, humans are able to use sensorimotor predictions to direct their gaze toward task-relevant feedback locations. Outcome-dependent saccade latency differences (miss vs. hit) indicate that also predictive valuation processes are involved in planning predictive saccades.
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