Metabotropic glutamate receptor 5 binding in patients with obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a disabling, mostly chronic, psychiatric condition with significant social and economic impairments and is a major public health issue. However, numerous patients are resistant to currently available pharmacological and psychological interventions. Given that recent animal studies and magnetic resonance spectroscopy research points to glutamate dysfunction in OCD, we investigated the metabotropic glutamate receptor 5 (mGluR5) in patients with OCD and healthy controls. We determined mGluR5 distribution volume ratio (DVR) in the brain of ten patients with OCD and ten healthy controls by using [11C]ABP688 positron-emission tomography. As a clinical measure of OCD severity, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was employed. We found no significant global difference in mGluR5 DVR between patients with OCD and healthy controls. We did, however, observe significant positive correlations between the Y-BOCS obsession sub-score and mGluR5 DVR in the cortico-striatal-thalamo-cortical brain circuit, including regions of the amygdala, anterior cingulate cortex, and medial orbitofrontal cortex (Spearman's ρ's⩾ = 0.68, p < 0.05). These results suggest that obsessions in particular might have an underlying glutamatergic pathology related to mGluR5. The research indicates that the development of metabotropic glutamate agents would be useful as a new treatment for OCD.

VIRTOPSY--scientific documentation, reconstruction and animation in forensic: individual and real 3D data based geo-metric approach including optical body/object surface and radiological CT/MRI scanning.

Until today, most of the documentation of forensic relevant medical findings is limited to traditional 2D photography, 2D conventional radiographs, sketches and verbal description. There are still some limitations of the classic documentation in forensic science especially if a 3D documentation is necessary. The goal of this paper is to demonstrate new 3D real data based geo-metric technology approaches. This paper present approaches to a 3D geo-metric documentation of injuries on the body surface and internal injuries in the living and deceased cases. Using modern imaging methods such as photogrammetry, optical surface and radiological CT/MRI scanning in combination it could be demonstrated that a real, full 3D data based individual documentation of the body surface and internal structures is possible in a non-invasive and non-destructive manner. Using the data merging/fusing and animation possibilities, it is possible to answer reconstructive questions of the dynamic development of patterned injuries (morphologic imprints) and to evaluate the possibility, that they are matchable or linkable to suspected injury-causing instruments. For the first time, to our knowledge, the method of optical and radiological 3D scanning was used to document the forensic relevant injuries of human body in combination with vehicle damages. By this complementary documentation approach, individual forensic real data based analysis and animation were possible linking body injuries to vehicle deformations or damages. These data allow conclusions to be drawn for automobile accident research, optimization of vehicle safety (pedestrian and passenger) and for further development of crash dummies. Real 3D data based documentation opens a new horizon for scientific reconstruction and animation by bringing added value and a real quality improvement in forensic science.

3D documentation and visualization of external injury findings by integration of simple photography in CT/MRI data sets (IprojeCT).

This study evaluated the feasibility of documenting patterned injury using three dimensions and true colour photography without complex 3D surface documentation methods. This method is based on a generated 3D surface model using radiologic slice images (CT) while the colour information is derived from photographs taken with commercially available cameras. The external patterned injuries were documented in 16 cases using digital photography as well as highly precise photogrammetry-supported 3D structured light scanning. The internal findings of these deceased were recorded using CT and MRI. For registration of the internal with the external data, two different types of radiographic markers were used and compared. The 3D surface model generated from CT slice images was linked with the photographs, and thereby digital true-colour 3D models of the patterned injuries could be created (Image projection onto CT/IprojeCT). In addition, these external models were merged with the models of the somatic interior. We demonstrated that 3D documentation and visualization of external injury findings by integration of digital photography in CT/MRI data sets is suitable for the 3D documentation of individual patterned injuries to a body. Nevertheless, this documentation method is not a substitution for photogrammetry and surface scanning, especially when the entire bodily surface is to be recorded in three dimensions including all external findings, and when precise data is required for comparing highly detailed injury features with the injury-inflicting tool.

Non-Contact Documentation of Physical Characteristics of Ecstasy Tablets, Hemp Coins, and Imprint Punches by using 3D Optical Surface Scanning

The description of seized illicit ecstasy tablets and other pressed drug products is an important step in casework. The physical and visual analysis and the description of the characteristics can be employed for intelligence purposes. Besides photography and manual measurements of dimensions, some optical instruments are employed for detailed measurements of physical characteristics. In this work, the method of 3D surface digitizing is introduced as a suitable tool for highly accurate documentation of small objects, especially for pressed drug products. The resulting detailed information about the geometry, and the results of an automatic comparison of apparently uniform tablets and coins with punches, can support drug intelligence.

Virtopsy in der Unfallrekonstruktion

Mit der Virtopsy hat das Institut für Rechtmedizin der Universität Bern unter Prof. Dr. med. R. Dirnhofer und Prof. Dr. med. M. Thali die Rechtsmedizin über die ganze Welt revolutioniert. Obwohl einzelne Techniken, aus dem klinischen Medizinalltag stammend, bereits zu früherer Zeit im einen oder andere Autopsie-Saal bereits zur Anwendung kamen, waren es die Berner Rechtsmediziner, Radiologen und Ingenieure, welche diese kombinierten. Unter dem Begriff Virtopsy vereint sich die Nutzung von medizinischen bildgebenden Verfahren mit dem Erfassen der Körperoberfläche mittels 3D-Oberflächenscanning. Dadurch hat Virtopsy, nebst den rekonstruktiven Möglichkeiten, ein immenses Potential für die Dokumentation sowohl vom Verstorbenen als auch von Verletzungen von Lebenden. Gerade mittels der räumlichen Darstellung von inneren Verletzungen und Frakturen können diese für den medizinischen Laien optimal dargestellt und verständlich gemacht werden. Bei der Klärung von Verkehrsunfällen, insbesondere bei Kollisionen von Motorfahrzeugen mit Fussgängern oder Zweiradfahrern - gegenüber welchen der Mensch besonders exponiert und verletzlich ist - aber auch zur Klärung von Verletzungen an Fahrzeuginsassen, zeigen sich die rekonstruktiven Möglichkeiten von Virtopsy. Dabei gilt zu beachten, dass die 3D-Dokumentation mittels den erwähnten Verfahren eine Akquisition von digitalen Daten, nicht automatisch eine vollständige Auswertung zur Folge haben muss. Trotzdem zeigt sich, dass viele offene Fragen erst im Nachhinein auftreten, wenn die Befunde und Spuren nicht mehr zugänglich sind. Die mittels Virtopsy erhobenen digitalen Daten lassen sich jedoch zu jedem Zeitpunkt neu befunden oder weiter bearbeiten und können auch in Zukunft zur Klärung eines Unfallereignisses beitragen.

Wer lenkte den PW?

Die Rekonstruktion von Verkehrsunfällen ist ein interdisziplinäres Arbeitsgebiet. Verschiedene Institutionen wie z.B. die Polizei, die Rechtsmedizin oder die Unfallanalyse befassen sich mit der Beantwortung von juristischen Fragestellungen bei Verkehrsunfällen. Die modernen 3D-Dokumentations- und Analysemethoden und der Einsatz der bildgebenden Verfahren in der Rechtsmedizin ermöglichen eine disziplinübergreifende Auswertung der vorhandenen Spuren und Befunde und eröffnen damit ganz neue Horizonte und Dimensionen. Zudem ermöglichen sie es auch dem technischen Laien, eine bildliche Vorstellung der komplexen unfalldynamischen Abläufe zu geben. Im vorliegenden Beitrag wird anhand eines Falles die interdisziplinäre Fallanalyse und morphometrische 3D-Rekonstruktion vorgestellt und erläutert. Dieser Fall wurde Jahre nach dem Ereignis in Auftrag gegeben zur Klärung der Frage, wer den PW zum Unfallzeitpunkt gelenkt hatte. Die morphometrische 3D-Rekonstruktion umfasst die Ermittlung des Unfallhergangs, des biomechanischen Verhaltens der Fahrzeuginsassen und der Entstehung ihrer Verletzungen sowie der Entstehung der Blutspuren und weiterer Spuren und Beschädigungen im Fahrzeuginneren. Die Fahrzeuginsassen werden mittels Photogrammetrie und optischem 3D-Oberflächenscanning dreidimensional dokumentiert. Von verletzten Insassen werden zusätzlich die Daten klinischer radiologischer Untersuchungen von verstorbenen die vor der Obduktion durchgeführte Computertomographie (CT) und Magnetresonanztomographie (MRT) in die 3D-Analyse integriert. Das Fahrzeug und alle unfallrelevanten Objekte werden ebenfalls mittels Photogrammetrie und 3D-Oberflächenscanning erfasst. Ein 3D- Situationsplan der Örtlichkeit mit allen Spuren wird von der Polizei mittels Photogrammetrie und Laserscanning erstellt und in die Auswertung integriert. Anhand dieser 3D-Daten, insbesondere der Spuren am Unfallort und der Beschädigungen des Fahrzeuges, wird der Unfallablauf und daraus resultierend das biomechanische Verhalten der Fahrzeuginsassen rekonstruiert und in der Animationssoftware 3DS Max Design nachgestellt. Basierend auf den gewonnenen Erkenntnissen können morphometrische Vergleiche der Verletzungen mit den relevanten Strukturen im Fahrzeuginneren durchgeführt und so ermittelt werden, wie diese Verletzungen entstanden sind und auf welchen Sitzen die Insassen während des Unfalles sassen. Neben den Verletzungen können auch die Körpergrössen der Insassen Hinweise zur Ermittlung des Lenkers geben. Die Möglichkeiten der morphometrischen Rekonstruktion mittels der 3D-Techniken sind weitreichend und können oft entscheidende Erkenntnisse für das Ermittlungsverfahren liefern.

Association of long-term nicotine abstinence with normal metabotropic glutamate receptor-5 binding

BACKGROUND Nicotine addiction is a major public health problem and is associated with primary glutamatergic dysfunction. We recently showed marked global reductions in metabotropic glutamate receptor type 5 (mGluR5) binding in smokers and recent ex-smokers (average abstinence duration of 25 weeks). The goal of this study was to examine the role of mGluR5 downregulation in nicotine addiction by investigating a group of long-term ex-smokers (abstinence >1.5 years), and to explore associations between mGluR5 binding and relapse in recent ex-smokers. METHODS Images of mGluR5 receptor binding were acquired in 14 long-term ex-smokers, using positron emission tomography with radiolabeled [11C]ABP688, which binds to an allosteric site with high specificity. RESULTS Long-term ex-smokers and individuals who had never smoked showed no differences in mGluR5 binding in any of the brain regions examined. Long-term ex-smokers showed significantly higher mGluR5 binding than recent ex-smokers, most prominently in the frontal cortex (42%) and thalamus (57%). CONCLUSIONS Our findings suggest that downregulation of mGluR5 is a pathogenetic mechanism underlying nicotine dependence and the high relapse rate in individuals previously exposed to nicotine. Therefore, mGluR5 receptor binding appears to be an effective biomarker in smoking and a promising target for the discovery of novel medication for nicotine dependence and other substance-related disorders.

High-resolution MALDI-FT-ICR MS imaging for the analysis of metabolites from formalin-fixed, paraffin-embedded clinical tissue samples.

We present the first analytical approach to demonstrate the in situ imaging of metabolites from formalin-fixed, paraffin-embedded (FFPE) human tissue samples. Using high-resolution matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometry imaging (MALDI-FT-ICR MSI), we conducted a proof-of-principle experiment comparing metabolite measurements from FFPE and fresh frozen tissue sections, and found an overlap of 72% amongst 1700 m/z species. In particular, we observed conservation of biomedically relevant information at the metabolite level in FFPE tissues. In biomedical applications, we analysed tissues from 350 different cancer patients and were able to discriminate between normal and tumour tissues, and different tumours from the same organ, and found an independent prognostic factor for patient survival. This study demonstrates the ability to measure metabolites in FFPE tissues using MALDI-FT-ICR MSI, which can then be assigned to histology and clinical parameters. Our approach is a major technical, histochemical, and clinicopathological advance that highlights the potential for investigating diseases in archived FFPE tissues.

Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation.

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis.