Heterogene chemo-enzymatische dynamisch kinetische Racematspaltung symmetrischer und asymmetrischer α-Hydroxyketone

Für die Herstellung pharmazeutisch interessanter α-Hydroxyketone ist die dynamsich kinetische Racematspaltung (DKR) der korrespondierenden Racemate eine interessante und leistungsfähige Methode. Die dafür benötigten Lipasen zeichnen sich insbesondere durch ihre Aktivität und Stabilität in rein organischen Lösungsmitteln aus. Der Verzicht von Cofaktoren macht diese Enzymklasse für einen industriellen Einsatz besonders attraktiv. Für α-Hydroxyketone mit großen Seitenketten hat sich die Lipase TL aus Pseudomonas stutzeri als Biokatalysator als am geeignetsten gezeigt. In vorherigen Studien wurde die Lipase TL erfolgreich mit dem homogenen Shvo-Katalysator für eine effektive DKR von Benzoin und Benzoinderivaten kombiniert und eine strikte (S)-Selektivität der Lipase TL festgestellt. In einer weiteren Studie wurde eine komplett heterogene DKR etabliert. Hierbei wurde die Lipase TL adsorptiv auf dem Polypropylenträger Accurel MP1001 immobilisiert und der Shvo-Katalysator durch verschiedene Metallkatalysatoren ersetzt. Als Modellsubstrat wurde Benzoin verwendet. Das beste Ergebnis der DKR von Benzoin wurde mit den Katalysator Zr-TUD-1 (25) im Lösungsmittel Toluol erreicht. Hauptziel dieser Arbeit war die Übertragung der heterogenen DKR von Benzoin auf weitere pharmazeutisch relevante α-Hydroxyketone. Dafür wurde zunächst eine generelle Optimierung der Immobilisierung der Lipase TL durch Verwendung verschiedener trägerbasierter und trägerloser Methoden und die Charakterisierung der Wasseraktivitätsabhängigkeit der KR und der Racemisierung durchgeführt. Zur Verbesserung der Umweltfreundlichkeit der Reaktion wurden außerdem alternative Lösungsmittel als Reaktionsmedium untersucht. Das optimierte Reaktionssystem wurde auf ausgewählte symmetrische und asymmetrische α-Hydroxyketone übertragen und die Eignung der Lipase TL sowie der CALB als Biokatalysatoren überprüft. Nach der Wahl der passenden Lipase wurde die DKR der ausgewählten α-Hydroxyketone untersucht und optimiert

Bestimmung der Eigenstabilität von enoralen Zirkondioxid-Implantaten

Den deutlichen biologischen Vorteilen von ZrO2-Implantaten steht eine möglicherweise geringere Stabilität im Interfacebereich gegenüber. Es sollte daher die mechanische Stabilität zweiteiliger vollkeramischer ZrO2-Implantate geprüft und mit der von Ti-Implantaten verglichen werden. Durch das technisch ausgereifte und in der Zahnheilkunde bereits erprobte Rotationsschwinger-Verfahren (DIN 1331-2) wurden verschiedene Typen von ZrO2-Implantaten (geteilte Formen mit verschiedenen Interface-Levels, zementierte und verschraubte Abutments mit ZrO2- und Titanschrauben, einteilige Kontroll-Implantate) pseudorealistischen Belastungen von 15 und 50 Ncm im life time-Modus ausgesetzt. Vor, während und nach den Stresstests wurden die Lockerung der Verbindungsschraube, das Kipp- und Drehspiel sowie die Bruchfestigkeit im Verbundbereich zwischen Fixtur und Abutment bestimmt. Frakturen im Interface-Bereich traten bei 15 Ncm-Belastung in 3 %, bei 50 Ncm in 26 % der Fälle auf. Als besonders bruchanfällig erwiesen sich Implantate mit zementiertem Abutment sowie sog. Bone Level-Implantate mit ZrO2-Schrauben. Die Lösedrehmomente (Restdrehmomente) betrugen für Titan-Schrauben 64 % und für solche aus ZrO2 nur noch 36 % des initialen Anzugsdrehmoments. Das höchste Drehspiel im Verbundbereich (+2,5°) wurde bei Bone Level-Implantaten mit ZrO2-Schrauben beobachtet. Das Kippspiel aller Implantate blieb während der Tests weitgehend unabhängig vom Material und einer Zementierung der Fixierungsschrauben relativ stabil. Die höchste mechanische Stabilität des Verbundbereichs wurde unter Berücksichtigung aller Testkriterien bei sog. Tissue Level-Implantaten, die mit Titan-Schrauben befestigt waren, beobachtet. Durch das Rotationsschwinger-Verfahren kann eine langjährige Belastung von Implantaten innerhalb kurzer Zeit simuliert werden. Im Vergleich zu Ti-Implantaten zeigten dabei ZrO2-Implantate weitgehend bessere Ergebnisse bezüglich Bruchfestigkeit, Abnützungs- und Lockerungseffekten im Bereich des Verbunds zwischen Fixtur und Abutment

Effects of a brief mindfulness meditation practice on Pavlovian-to-instrumental transfer in alcohol use disorder – a pilot study

IntroductionPavlovian conditioned contextual cues have been suggested to modulate instrumental action and might explain maladaptive behavior such as relapse in participants suffering from alcohol use disorder (AUD). Pavlovian-to-Instrumental transfer (PIT) experimentally assesses the magnitude of this context-dependent effect and studies have shown a larger PIT effect in AUD populations. Taken this into account, a reduction of the influence of cues on behavior seems warranted and one approach that could alter such cue reactivity is mindfulness. Mindfulness-based interventions have been shown to be efficient in the treatment of AUD, but underlying mechanisms are yet to be elucidated. Therefore, we aim at investigating the effect of a brief mindful body scan meditation on the magnitude of the PIT effect in AUD subjects and matched controls.MethodsUsing a randomized within-subjects design, we compared the effect of a short audio guided body scan meditation against a control condition (audio of nature sounds) on PIT in healthy (n = 35) and AUD (n = 27) participants.ResultsWe found no differences in PIT effect between healthy and AUD participants as well as between conditions. However, a significant interaction effect points to a decreased PIT effect after body scan meditation in AUD subjects only.DiscussionThese pilot results suggest that AUD might be susceptible to mindfulness-induced changes in PIT, with these findings contributing to entangling the underlying mechanisms of the efficacy of mindfulness-based interventions in AUD. However, further investigation should confirm these preliminary results and the efficacy of mindfulness meditation practice in decreasing the PIT effect

Volumetric Prefrontal Cortex Alterations in Patients With Alcohol Dependence and the Involvement of Self‐Control

Background: Aspects of self-control such as sensation seeking and impaired impulse control have been implicated in alcohol dependence (ALC). Conversely, sensation seeking has been ascribed a possible protective role in stress-related psychopathologies. We therefore examined gray matter (GM) morphology in individuals with ALC, focusing on differences in prefrontal regions that have been associated with self-control. Additionally, we accounted for differences in lifetime alcohol intake regarding self-control measures and cortical structures in ALC patients. Methods: With voxel-based morphometry (VBM) focusing on prefrontal a priori defined regions of interest, we assessed a group of 62 detoxified ALC patients and 62 healthy controls (HC). ALC patients were subsequently divided into high (n = 9) and low consumers (n = 53). Self-control was assessed by use of the Barratt Impulsiveness Scale and the Sensation Seeking Scale. Results: Compared to HC, ALC had significantly less GM volume in bilateral middle frontal gyrus (MFG) and right medial prefrontal cortex as well as in the right anterior cingulate. High-consuming ALC showed smaller GM in right orbitofrontal cortex as well as lower sensation seeking scores than low consumers. In low-consuming ALC, right MFG-GM was positively associated with magnitude of sensation seeking; particularly, larger MFG-GM correlated with greater thrill and adventure seeking. Conclusion: Thus, our findings (i) indicate deficient GM volume in prefrontal areas related to self-control and (ii) might accentuate the phenotypic divergence of ALC patients and emphasize the importance of the development of individual treatment options

Pathology of Echinococcosis

Infection of humans by the larval stage of the tapeworms Echinococcus granulosus sensu lato or Echinococcus multilocularis causes the life-threatening zoonoses cystic echinococcosis (CE) and alveolar echinococcosis (AE). Although cystic liver lesions are a hallmark of both diseases, course, prognosis, and patients' management decisively differ between the two. The wide and overlapping spectrum of morphologies and the limited availability of ancillary tools are challenges for pathologists to reliably diagnose and subtype echinococcosis. Here, we systematically and quantitatively recorded the pathologic spectrum in a clinically and molecularly defined echinococcosis cohort (138 specimens from 112 patients). Immunohistochemistry using a novel monoclonal antibody (mAbEmG3) was implemented, including its combined application with the mAbEm2G11. Six morphologic criteria sufficiently discriminated between CE and AE: size of smallest (CE/AE: >2/≤2 mm) and largest cyst (CE/AE: >25/≤25 mm), thickness of laminated layer (CE/AE: >0.15/≤0.15 mm) and pericystic fibrosis (CE/AE: >0.6/≤0.6 mm), striation of laminated layer (CE/AE: moderate-strong/weak), and number of cysts (CE/AE: ≤9/>9). Combined immunohistochemistry with mAbEm2G11 (E. multilocularis specific) and mAbEmG3 (reactive in AE and CE) was equally specific as and occasionally more sensitive than polymerase chain reaction. On the basis of these findings, we developed a diagnostic algorithm for the differential diagnosis of echinococcosis. In summary, we have not only identified the means to diagnose echinococcosis with greater certainty, but also defined morphologic criteria, which robustly discriminate between CE and AE. We expect our findings to improve echinococcosis diagnostics, especially of challenging cases, beneficially impacting the management of echinococcosis patients

Pathology of Echinococcosis: A Morphologic and Immunohistochemical Study on 138 Specimens With Focus on the Differential Diagnosis Between Cystic and Alveolar Echinococcosis.

Infection of humans by the larval stage of the tapeworms Echinococcus granulosus sensu lato or Echinococcus multilocularis causes the life-threatening zoonoses cystic echinococcosis (CE) and alveolar echinococcosis (AE). Although cystic liver lesions are a hallmark of both diseases, course, prognosis, and patients' management decisively differ between the two. The wide and overlapping spectrum of morphologies and the limited availability of ancillary tools are challenges for pathologists to reliably diagnose and subtype echinococcosis. Here, we systematically and quantitatively recorded the pathologic spectrum in a clinically and molecularly defined echinococcosis cohort (138 specimens from 112 patients). Immunohistochemistry using a novel monoclonal antibody (mAbEmG3) was implemented, including its combined application with the mAbEm2G11. Six morphologic criteria sufficiently discriminated between CE and AE: size of smallest (CE/AE: >2/≤2 mm) and largest cyst (CE/AE: >25/≤25 mm), thickness of laminated layer (CE/AE: >0.15/≤0.15 mm) and pericystic fibrosis (CE/AE: >0.6/≤0.6 mm), striation of laminated layer (CE/AE: moderate-strong/weak), and number of cysts (CE/AE: ≤9/>9). Combined immunohistochemistry with mAbEm2G11 (E. multilocularis specific) and mAbEmG3 (reactive in AE and CE) was equally specific as and occasionally more sensitive than polymerase chain reaction. On the basis of these findings, we developed a diagnostic algorithm for the differential diagnosis of echinococcosis. In summary, we have not only identified the means to diagnose echinococcosis with greater certainty, but also defined morphologic criteria, which robustly discriminate between CE and AE. We expect our findings to improve echinococcosis diagnostics, especially of challenging cases, beneficially impacting the management of echinococcosis patients

From representing views to representativeness of views: illustrating a new (Q2S) approach in the context of health care priority setting in nine European countries

Governments across Europe are required to make decisions about how best to allocate scarce health care resources. There are legitimate arguments for eliciting societal vales in relation to health care resource allocation given the roles of the general public as payers and potential patients. However, relatively little is known about the views of the general public on general principles which could guide these decisions. In this paper we present five societal viewpoints on principles for health care resources allocation and develop a new approach, Q2S, designed to investigate the extent to which these views are held across a range of European countries. An online survey was developed, based on a previously completed study Q methodology, and delivered between November 2009 and February 2010 across nine countries to 33,515 respondents. The largest proportion of our respondents (44%), were found to most associate themselves with an egalitarian perspective. Differences in views were more strongly associated with countries than with socio-demographic characteristics. These results provide information which could be useful for decision makers in understanding the pluralistic context in which they are making health care resource allocation decisions and how different groups in society may respond to such decisions

Mobile Air Quality Studies (MAQS) - an international project

Due to an increasing awareness of the potential hazardousness of air pollutants, new laws, rules and guidelines have recently been implemented globally. In this respect, numerous studies have addressed traffic-related exposure to particulate matter using stationary technology so far. By contrast, only few studies used the advanced technology of mobile exposure analysis. The Mobile Air Quality Study (MAQS) addresses the issue of air pollutant exposure by combining advanced high-granularity spatial-temporal analysis with vehicle-mounted, person-mounted and roadside sensors. The MAQS-platform will be used by international collaborators in order 1) to assess air pollutant exposure in relation to road structure, 2) to assess air pollutant exposure in relation to traffic density, 3) to assess air pollutant exposure in relation to weather conditions, 4) to compare exposure within vehicles between front and back seat (children) positions, and 5) to evaluate "traffic zone"- exposure in relation to non-"traffic zone"-exposure. Primarily, the MAQS-platform will focus on particulate matter. With the establishment of advanced mobile analysis tools, it is planed to extend the analysis to other pollutants including including NO2, SO2, nanoparticles, and ozone