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Schwerk A.,Charite University of Medicine | Pouwels P.J.W.,VU University Amsterdam | Van Amelsvoort T.,Maastricht University
Journal of Neurochemistry | Year: 2014

By reviewing the existing 1H-magnetic resonance spectroscopy literature in schizophrenia, the relationship of different sample characteristics and applied methodologies with metabolite alterations is explored. Furthermore, we emphasize common pitfalls and discrepancies in the methodological framework of the reviewed studies that introduce unwanted variation in findings and complicate the comparison of studies. A total of 92 studies were reviewed. Articles were retrieved by searching the Pubmed database. Care was taken to note down reliability and validity measures of each included study. Despite many methodological differences and shortcomings, progressive NAA reductions could be seen in several brain regions implicated in the pathogenesis of schizophrenia. In terms of treatment effects, cross-sectional evidence implicates a normalizing role for atypical antipsychotic medication; however, longitudinal studies remain inconclusive on this issue. Choline, creatine, and myo-inositol levels remain largely unchanged and a time-dependent role of glutamate finds confirmation in several spectroscopy studies. Other findings are less consistent and need further replication. Most studies lack power and methodological precision. Future studies should aim for standardization and for more distinguished study populations to gain more valid and reliable findings. © 2013 International Society for Neurochemistry.

Strubing F.,Leibniz University of Hanover | Ruiz M.H.,Leibniz University of Hanover | Ruiz M.H.,Charite University of Medicine | Jabusch H.C.,Leibniz University of Hanover | And 2 more authors.
Annals of the New York Academy of Sciences | Year: 2012

Musician's dystonia (MD) is a task-specific movement disorder characterized by a loss of voluntary motor control in highly trained movements like piano playing. Its underlying pathophysiology is defined by deficient functioning of neural pathways at different levels of the central nervous system. However, a few studies have examined the brain responses associated with executive functions such as error monitoring in MD. We recorded the electroencephalogram (EEG) in professional pianists during the performance of memorized music sequences at fast tempi. Event-related potentials (ERPs) locked to pitch errors were investigated in MD and a control group. In MD patients, significantly larger error-related brain responses before and following errors were observed as compared with healthy pianists. Our results suggest that in MD, the generalized degraded neural activity at all levels of the central nervous system is manifested in specific neural correlates of the executive functions that monitor an overlearned sensorimotor performance. © 2012 New York Academy of Sciences.

Mosleh I.M.,University of Jordan | Shonian G.,Charite University of Medicine | Geith E.,South Shuneh Hospital | Al-Jawabreh A.,Leishmania Research Unit | Natsheh L.,University of Jordan
Experimental Parasitology | Year: 2015

The identity of the causative species of cutaneous leishmaniasis (CL) in the endemic Jordanian Mid Jordan Valley (JMidJV) was investigated using the polymerase chain reaction (PCR) amplifying the ribosomal internal transcribed spacer 1 (ITS-1) followed by the restriction fragment length polymorphism (RFLP). The geographical distribution of CL and the usefulness of ITS1 PCR in diagnosis of suspected CL in the study area were also addressed. Over the period from 2004 to 2009, 56 clinical isolates of Leishmania promastigotes and 185 lesion scrapings spotted on filter papers were obtained from suspected CL patients living in the JMidJV, which is divided into northern and southern districts. The majority (67.1%) of patients occurred in the populated eastern part of the southern district. Of the 185 suspected CL patients, 173 (93.5%) were confirmed positive using PCR. Leishmanial DNA was detected in 27 (90%) of 30 patients having clinically atypical lesions of CL and in 60 (92%) of 65 smear- and culture-negative cases having typical lesions of CL. The parasites in all of the 56 isolates and the 173 PCR-positive scrapings were classified as Leishmania major. In conclusion, PCR is useful in diagnosis of CL especially when smear and culture are negative. It is also recommended as a differential diagnostic tool of atypical lesions when CL is endemic. The identification of L.major as the causative species in such a considerable number of CL cases, representative of all mini foci of CL in the study area, shows that the JMidJV is a classic focus of L.major. © 2014 Elsevier Inc.

Humme D.,Charite University of Medicine | Lukowsky A.,Charite University of Medicine | Sterry W.,Charite University of Medicine
Giornale Italiano di Dermatologia e Venereologia | Year: 2010

Cutaneous T-cell lymphomas (CTCL) represent clonal proliferations of neoplastic skin homing T-cells. Within the group of primary CTCL, mycosis fungoides (MF) is the most common entity, affecting the skin as a primary site. MF initially presents in the skin with a slow indolent course of a characteristic stepwise progression from patches to plaques and tumors accompanied by distinctive histological changes. Routine diagnosis is based on these clinical and histological features. However, due to similarities with benign lymphoproliferative or reactive skin diseases, especially at the initial presentation of the disease, diagnosis can be difficult. Although the etiology of mycosis fungoides is still unknown, important insights have been gained in the immunological and genetic perturbations, which are associated with the disease. In the last years the emergence of molecular genetic techniques allowing to analyze the clonality status in lymphocytic infiltrates, has provided new tools with the potential to increase the accuracy of diagnosis, staging and therefore stage-adapted treatment. Nevertheless, it is important to notice that some limitations restrict the predictive value of the results obtained by these analyses. Diagnostic tool of MF, including clinical, histo- and immunohistological findings as well as molecular genetic analysis will be covered in this review.

Chassidim Y.,Ben - Gurion University of the Negev | Vazana U.,Ben - Gurion University of the Negev | Prager O.,Ben - Gurion University of the Negev | Veksler R.,Ben - Gurion University of the Negev | And 5 more authors.
Seminars in Cell and Developmental Biology | Year: 2015

A dysfunctional BBB is a common feature in a variety of brain disorders, a fact stressing the need for diagnostic tools designed to assess brain vessels' permeability in space and time. Biological research has benefited over the years various means to analyze BBB integrity. The use of biomarkers for improper BBB functionality is abundant. Systemic administration of BBB impermeable tracers can both visualize brain regions characterized by BBB impairment, as well as lead to its quantification. Additionally, locating molecular, physiological content in regions from which it is restricted under normal BBB functionality undoubtedly indicates brain pathology-related BBB disruption. However, in-depth research into the BBB's phenotype demands higher analytical complexity than functional vs. pathological BBB; criteria which biomarker based BBB permeability analyses do not meet. The involvement of accurate and engineering sciences in recent brain research, has led to improvements in the field, in the form of more accurate, sensitive imaging-based methods. Improvements in the spatiotemporal resolution of many imaging modalities and in image processing techniques, make up for the inadequacies of biomarker based analyses. In pre-clinical research, imaging approaches involving invasive procedures, enable microscopic evaluation of BBB integrity, and benefit high levels of sensitivity and accuracy. However, invasive techniques may alter normal physiological function, thus generating a modality-based impact on vessel's permeability, which needs to be corrected for. Non-invasive approaches do not affect proper functionality of the inspected system, but lack in spatiotemporal resolution. Nevertheless, the benefit of medical imaging, even in pre-clinical phases, outweighs its disadvantages. The innovations in pre-clinical imaging and the development of novel processing techniques, have led to their implementation in clinical use as well. Specialized analyses of vessels' permeability add valuable information to standard anatomical inspections which do not take the latter into consideration. © 2014 Elsevier Ltd.

Jung T.M.,Charite University of Medicine | Lubowicki A.,Charite University of Medicine | Wienand A.,Charite University of Medicine | Wagner M.,Sporthopaedicum | Weiler A.,Sporthopaedicum
Arthroscopy - Journal of Arthroscopic and Related Surgery | Year: 2011

Purpose: To analyze outcome differences after posterior cruciate ligament (PCL) reconstruction in male and female patients. Methods: A prospective database of 234 PCL reconstructions (53 female and 181 male patients) with either isolated or combined procedures was analyzed. Patients were followed up for a mean of 62 months (range, 34 to 110 months) by use of stress radiography and the International Knee Documentation Committee score. We included 32 female patients for a matched-group analysis and compared them with 32 matching male patients. Matching parameters were number/type of reconstructed ligaments, revision/primary surgery, autograft/allograft use, preoperative tibial displacement, time interval from injury to surgery, follow-up interval, and age. Results: There was no preoperative difference in posterior stress radiographs (12.9 ± 3.0 mm in female patients and 13.2 ± 2.3 mm in male patients). After surgery, both groups showed a significant reduction in posterior displacement (6.0 ± 2.5 mm [54% reduction] in female patients and 7.8 ± 2.2 mm [40% reduction] in male patients). There was a significant greater reduction of posterior laxity in female patients. International Knee Documentation Committee scoring showed a significant improvement in both groups. Conclusions: We found in this specific patient series a superior reduction of posterior tibial laxity in female patients compared with male patients, indicating that possible gender-related differences exist after PCL surgery. Level of Evidence: Level III, retrospective comparative study using prospective data. © 2011 Arthroscopy Association of North America.

Gansukh T.,Medical Research Institute of Mongolia | Donizy P.,Wroclaw Medical University | Halon A.,Wroclaw Medical University | Lage H.,Charite University of Medicine | Surowiak P.,Wroclaw Medical University
Anticancer Research | Year: 2013

Background: Cisplatin-based therapy is a pivotal type of chemotherapy for non-small cell lung cancer (NSCLC) and chemoresistance to cisplatin represents one of the most significant barriers to improving long-term clinical outcomes. Materials and Methods: The present study aimed at examining metallothionein (MT) expression in six NSCLC cell lines as well as examining effects of exposure to cisplatin on MT expression in the most cisplatin-resistant (97/97) and the cisplatin-sensitive (DV90) cell lines. Results: The most cisplatin-resistant NSCLC cell line [97/97; (IC50)= 4.659 μM] exposed to the highest concentration of cisplatin (10 μM) exhibited decreased nuclear MT expression (MTn=6) compared to cells cultured in medium with a lower concentration of cisplatin (0, 1 and 5 μM) (MTn=12). A higher cytoplasmic metallothionein expression (MTc=6) was found in the 97/97 cell line exposed to the highest concentration of cisplatin (10 μM), compared to cells cultured in the medium with lower concentrations of cisplatin (0, 1 and 5 μM) (MTc=3). The most cisplatin-sensitive NSCLC cell line (DV90; IC50=0.184 μM) was characterized by a significant decrease of both nuclear and cytoplasmic MT expression with increasing cisplatin concentrations (5 vs. 10 μM). Conclusion: Nuclear and cytoplasmic expression of MT has no significant impact on the development of cisplatichemoresistance in NSCLC cell lines. The present study suggests that cisplatin resistance in NSCLC is metallothionein- independent.

Sanzleon P.,Institute Of Neurosciences Des Systemes | Knock S.A.,Charite University of Medicine | Woodman M.M.,Institute Of Neurosciences Des Systemes | Domide L.,Codemart | And 3 more authors.
Frontiers in Neuroinformatics | Year: 2013

We present TheVirtualBrain (TVB), a neuroinformatics platform for full brain network simulations using biologically realistic connectivity. This simulation environment enables the model-based inference of neurophysiological mechanisms across different brain scales that underlie the generation of macroscopic neuroimaging signals including functional MRI (fMRI), EEG and MEG. Researchers from different backgrounds can benefit from an integrative software platform including a supporting framework for data management (generation, organization, storage, integration and sharing) and a simulation core written in Python. TVB allows the reproduction and evaluation of personalized configurations of the brain by using individual subject data. This personalization facilitates an exploration of the consequences of pathological changes in the system, permitting to investigate potential ways to counteract such unfavorable processes. The architecture of TVB supports interaction with MATLAB packages, for example, the well known Brain Connectivity Toolbox. TVB can be used in a client-server configuration, such that it can be remotely accessed through the Internet thanks to its web-based HTML5, JS and WebGL graphical user interface. TVB is also accessible as a standalone cross-platform Python library and application, and users can interact with the scientific core through the scripting interface IDLE, enabling easy modeling, development and debugging of the scientific kernel. This second interface makes TVB extensible by combining it with other libraries and modules developed by the Python scientific community. In this article, we describe the theoretical background and foundations that led to the development of TVB, the architecture and features of its major software components as well as potential neuroscience applications. © 2013 Sanz_leon, Knock, Woodman, Domide, Mersmann, Mcintosh and Jirsa.

Ledet E.H.,Rensselaer Polytechnic Institute | D'Lima D.,Scripps Research Institute | Westerhoff P.,Charite University of Medicine | Szivek J.A.,University of Arizona | And 2 more authors.
Journal of the American Academy of Orthopaedic Surgeons | Year: 2012

For decades, implantable sensors have been used in research to provide comprehensive understanding of the biomechanics of the human musculoskeletal system. These complex sensor systems have improved our understanding of the in vivo environment by yielding in vivo measurements of force, torque, pressure, and temperature. Historically, implants have been modified to be used as vehicles for sensors and telemetry systems. Recently, microfabrication and nanofabrication technology have sufficiently evolved that wireless, passive sensor systems can be incorporated into implants or tissue with minimal or no modification to the host implant. At the same time, sensor technology costs per unit have become less expensive, providing opportunities for use in daily clinical practice. Although diagnostic implantable sensors can be used clinically without significant increases in expense or surgical time, to date, orthopaedic smart implants have been used exclusively as research tools. These implantable sensors can facilitate personalized medicine by providing exquisitely accurate in vivo data unique to each patient.

Diekmann F.,Charite University of Medicine | Schmitzberger F.F.,Charite University of Medicine | Fallenberg E.M.,Charite University of Medicine | Lawaczeck R.,Charite University of Medicine | And 7 more authors.
Radiology | Year: 2011

Purpose: To demonstrate the feasibility of low-dose photon-counting tomosynthesis in combination with a contrast agent (contrast material-enhanced tomographic mammography) for the differentiation of breast cancer. Materials and Methods: All studies were approved by the institutional review board, and all patients provided written informed consent. A phantom model with wells of iodinated contrast material (3 mg of iodine per milliliter) 1, 2, 5, 10, and 15 mm in diameter was assessed. Nine patients with malignant lesions and one with a high-risk lesion (atypical papilloma) were included (all women; mean age, 60 7 years). A multislit photon-counting tomosynthesis system was utilized (spectral imaging) to produce both low- and high-energy tomographic data (below and above the k edge of iodine, respectively ) in a single scan, which allowed for dual-energy visualization of iodine. Images were obtained prior to contrast material administration and 120 and 480 seconds after contrast material administration. Four readers independently assessed the images along with conventional mammograms, ultrasonographic images, and magnetic resonance images. Glandular dose was estimated. Results: Contrast agent was visible in the phantom model with simulated spherical tumor diameters as small as 5 mm. The average glandular dose was measured as 0.42 mGy per complete spectral imaging tomosynthesis scan of one breast. Because there were three time points (prior to contrast medium administration and 120 and 480 seconds after contrast medium administration), this resulted in a total dose of 1.26 mGy for the whole procedure in the breast with the abnormality. Seven of 10 cases were categorized as Breast Imaging Reporting and Data System score of 4 or higher by all four readers when reviewing spectral images in combination with mammograms. One lesion near the chest wall was not captured on the spectral image because of a positioning problem. Conclusion: The use of contrast-enhanced tomographic mammography has been demonstrated successfully in patients with promising diagnostic benefit. Further studies are necessary to fully assess diagnostic sensitivity and specificity. © RSNA, 2011. © RSNA, 2011.

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