Die Taphozönose des Fischschiefers (Rupelium/Oligozän) der Paläogen-Scholle Wiesloch-Rot (Baden-Württemberg/Deutschland)

Der unteroligozäne Fischschiefer der Paläogen-Scholle „Wiesloch-Rot“ wird unter der Berücksichtigung der Sedimentologie, Stratigraphie, Taxonomie, Diversität, Taphonomie und Paläoökologie untersucht. Die Sedimente dieser Scholle am östlichen Rand des Oberrheingrabens werden der Hochberg-Subformation innerhalb der Bodenheim-Formation zugeordnet. Die schwarzgrauen Ton- und Siltwechsellagerungen wurden während einer Transgression im einstigen Rupelmeer abgelagert. Sedimentologische Analysen an einem aufgenommen Profil der Tongrube Unterfeld bei Rauenberg zeigen, dass der Faulschlamm zeitweise sowohl über als auch unter der Sturmwellenbasis abgelagert wurde. Unterhalb der Sturmwellenbasis bildeten sich in einem hyp- bis anoxischen Stillwasserbereich fein laminierte Schichten ohne Bioturbation. Die Sturmwellenbasis erreichte durch heftige Sturmereignisse oder Meeresspiegelschwankungen zeitweise den Meeresboden und verwirbelte die laminierten Faulschlammlagen. Das führte zur Ablagerung von ungeschichteten, massigen Ton- und Siltsteineinlagen. Der Fischschiefer zeichnet sich durch eine diverse Tapho- und Thanatozönose aus. Pflanzen (Embryophyta) und Knochenfische (Teleostei) sind abundant und hoch divers. Anhand der Taxonomie und Taphonomie der Pflanzenfossilien erfolgt eine Einteilung in vier Assoziationen: Seegraswiesen entlang der Offshore-Rampe, litorale Sumpfgebiete, immergrüne Laubmischwälder im unmittelbaren Hinterland und die Gemeinschaft der submontanen Stufe am östlichen Rand des Oberrheingrabens. Marine Wirbellose (Gastropoda, Bivalvia, Echinodermata, Crustaceae), Knorpelfische (Chondrichthyes) und marine Landwirbeltiere (Testudinata, Sirenia) sind im Vergleich zu den oben genannten Gruppen selten und bestätigen ein lebensfeindliches Ablagerungsmilieu. Die Erhaltung terrestrischer Wirbellose (Araneae, Insecta) und Landwirbeltiere (Aves, Microchiroptera, Creodonta) belegt die küstennahe Lage des Ablagerungsraumes. Die taphonomische Analyse der Fossilien spricht für eine allochthone Herkunft und für eine Taphozönose, welche durch eine Vielzahl von umgebenden Ökosystemen gespeist wurde. Eine paläobiogeographische Analyse der Fischtaxa bestätigt, dass die Fischschiefer-Vergesellschaftung unter einem nördlichen und einem südlichen Fauneneinfluss stand. Der starke südliche Fauneneinfluss aus der Paratethys spricht für eine marine Verbindung zum Rupelmeer zur Ablagerungszeit des Fischschiefers. Die Kenntnis über die vertikale Häufigkeitsverteilung der Fossilien aus der wissenschaftlichen Grabung ermöglicht eine Rekonstruktion des Ablagerungsmodells für den Fischschiefer der Paläogen-Scholle „Wiesloch-Rot“. Die korrelierenden Häufigkeitsverteilungen von Fossilien aus den Seegraswiesen und den litoralen Waldgebieten belegen die ehemalige Existenz von Seegraswiesen im Osten des Ablagerungsbereiches. Sie waren der Küste vorgelagert. Der schwankende Eintrag aus diesen Liefergebieten steht gegensätzlich zu dem stetigen Eintrag von Überresten pelagischer Taxa aus dem Rupelmeer. Es wird für den östlichen Rand des Rupelmeeres eine nach Westen abfallenden Relief angenommen. Dadurch unterbrach bei einem Meeresspiegelrückgang zeitweise die Verbindung zwischen dem Ablagerungsbereich und den litoralen Vegetationszonen. Die Verbindung zum Rupelmeer im Westen bestand dabei weiter. Sturmereignisse hatten ebenfalls einen Einfluss auf den Eintrag aus den umliegenden Biozönosen. Der Fischschiefer der Paläogen-Scholle „Wiesloch-Rot“ bildete sich in einer Bucht oder Meeresbecken in einer Wassertiefe von weniger als 50 m am östlichen Rand des Oberrheingrabens mit einer Verbindung zum Rupelmeer. Weit entfernte Süßwassereinflüsse und gelegentliche Algenblüten führten zu einer Stratifizierung der Wassersäule mit salzarmen, sauerstoffreichen Oberflächenwasser und salzreichen, sauerstofffreien Tiefenwässern. Letztere hatten eine Mächtigkeit von nur wenigen 100 mm. Ungeachtet dessen haben die taxonomischen und taphonomischen Analysen gezeigt, dass auch das Oberflächenwasser nur spärlich besiedelt war und der Fischschiefer seinen Artenreichtum den lebensfreundlichen Bereichen in der Umgebung zu verdanken hat

The Liver-Selective Thyromimetic T-0681 Influences Reverse Cholesterol Transport and Atherosclerosis Development in Mice

Liver-selective thyromimetics have been reported to efficiently reduce plasma cholesterol through the hepatic induction of both, the low-density lipoprotein receptor (LDLr) and the high-density lipoprotein (HDL) receptor; the scavenger receptor class B type I (SR-BI). Here, we investigated the effect of the thyromimetic T-0681 on reverse cholesterol transport (RCT) and atherosclerosis, and studied the underlying mechanisms using different mouse models, including mice lacking LDLr, SR-BI, and apoE, as well as CETP transgenic mice.T-0681 treatment promoted bile acid production and biliary sterol secretion consistently in the majority of the studied mouse models, which was associated with a marked reduction of plasma cholesterol. Using an assay of macrophage RCT in mice, we found T-0681 to significantly increase fecal excretion of macrophage-derived neutral and acidic sterols. No positive effect on RCT was found in CETP transgenic mice, most likely due to the observed decrease in plasma CETP mass. Studies in SR-BI KO and LDLr KO mice suggested hepatic LDLr to be necessary for the action of T-0681 on lipid metabolism, as the compound did not have any influence on plasma cholesterol levels in mice lacking this receptor. Finally, prolonged treatment with T-0681 reduced the development of atherosclerosis by 60% in apoE KOs on Western type diet. In contrast, at an earlier time-point T-0681 slightly increased small fatty streak lesions, in part due to an impaired macrophage cholesterol efflux capacity, when compared to controls.The present results show that liver-selective thyromimetics can promote RCT and that such compounds may protect from atherosclerosis partly through induction of bile acid metabolism and biliary sterol secretion. On-going clinical trials will show whether selective thyromimetics do prevent atherosclerosis also in humans

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Hypnotherapy compared to cognitive-behavioral therapy for smoking cessation in a randomized controlled trial

Worldwide, more than eight million people die each year as a result of tobacco use. A large proportion of smokers who want to quit are interested in alternative smoking cessation methods, of which hypnotherapy is the most popular. However, the efficacy of hypnotherapy as a tobacco cessation intervention cannot be considered sufficiently proven due to significant methodological limitations in the studies available to date. The aim of the present study was to compare the efficacy of a hypnotherapeutic group program for smoking cessation with that of an established cognitive-behavioral group program in a randomized controlled trial. A total of 360 smokers who were willing to quit were randomly assigned to either hypnotherapy (HT) or cognitive-behavioral therapy (CBT) at two study sites, without regard to treatment preference. They each underwent a 6 weeks smoking cessation course (one 90 min group session per week) and were followed up at regular intervals over a 12 months period. The primary outcome variable was defined as continuous abstinence from smoking according to the Russell standard, verified by a carbon monoxide measurement at three measurement time points. Secondary outcome variables were 7 days point prevalence abstinence during the 12 months follow up and the number of cigarettes the non-quitters smoked per smoking day (smoking intensity). Generalized estimating equations were used to test treatment condition, hypnotic suggestibility, and treatment expectancy as predictors of abstinence. The two interventions did not differ significantly in the proportion of participants who remained continuously abstinent throughout the follow-up period (CBT: 15.6%, HT: 15.0%) and also regarding the 7 days abstinence rates during the 12 months follow-up (CBT: 21.2%, HT: 16.7%). However, when controlling for hypnotic suggestibility, CBT showed significantly higher 7 days abstinence rates. In terms of the continuous abstinence rates, it can be concluded that the efficacy of hypnotherapeutic methods for smoking cessation seem to be comparable to established programs such as CBT.Clinical trial registrationClinicalTrials.gov, identifier NCT01129999

Table_1_Hypnotherapy compared to cognitive-behavioral therapy for smoking cessation in a randomized controlled trial.DOCX

Worldwide, more than eight million people die each year as a result of tobacco use. A large proportion of smokers who want to quit are interested in alternative smoking cessation methods, of which hypnotherapy is the most popular. However, the efficacy of hypnotherapy as a tobacco cessation intervention cannot be considered sufficiently proven due to significant methodological limitations in the studies available to date. The aim of the present study was to compare the efficacy of a hypnotherapeutic group program for smoking cessation with that of an established cognitive-behavioral group program in a randomized controlled trial. A total of 360 smokers who were willing to quit were randomly assigned to either hypnotherapy (HT) or cognitive-behavioral therapy (CBT) at two study sites, without regard to treatment preference. They each underwent a 6 weeks smoking cessation course (one 90 min group session per week) and were followed up at regular intervals over a 12 months period. The primary outcome variable was defined as continuous abstinence from smoking according to the Russell standard, verified by a carbon monoxide measurement at three measurement time points. Secondary outcome variables were 7 days point prevalence abstinence during the 12 months follow up and the number of cigarettes the non-quitters smoked per smoking day (smoking intensity). Generalized estimating equations were used to test treatment condition, hypnotic suggestibility, and treatment expectancy as predictors of abstinence. The two interventions did not differ significantly in the proportion of participants who remained continuously abstinent throughout the follow-up period (CBT: 15.6%, HT: 15.0%) and also regarding the 7 days abstinence rates during the 12 months follow-up (CBT: 21.2%, HT: 16.7%). However, when controlling for hypnotic suggestibility, CBT showed significantly higher 7 days abstinence rates. In terms of the continuous abstinence rates, it can be concluded that the efficacy of hypnotherapeutic methods for smoking cessation seem to be comparable to established programs such as CBT.Clinical trial registrationClinicalTrials.gov, identifier NCT01129999.</p

Influence of T-0681 on macrophage reverse cholesterol transport <i>in vivo</i>.

<p>(A) WT mice were treated with T-0681 (36 nmol/kg/d) or PBS, and the treatment was continued during the 48-hours RCT study. 12 days into treatment, cholesterol-loaded, [³H]-labeled J774 macrophages were injected intraperitoneally, and 48 hours later tracer was measured in plasma, liver, and fecal sterols (N = 10). (B) Macrophage <i>in vivo</i> RCT in CETP Tg mice was performed as described in (A) (N = 5); inset: Western blot showing hepatic expression of LDLr and SR-BI; each lane represents pooled protein extracts from 5 mice per group. **<i>P</i><0.01, ***<i>P</i><0.001 versus corresponding control.</p

Influence of T-0681 on atherosclerosis development in apoE KO mice.

<p>Western type diet-fed apoE KOs were treated with T-0681 (36 nmol/kg/d) or PBS for 4 weeks (A, B) (N = 7) and 8 weeks (C, D) (N = 10). (A, C) FPLC analysis of pooled plasma from control and T-0681-treated mice. (B, D) Statistical comparison of the atherosclerotic lesion size in histological sections from the aortic root. ***<i>P</i><0.001 versus corresponding control.</p