Combined diffusion-weighted and functional magnetic resonance imaging reveals a temporal-occipital network involved in auditory-visual object processing

Functional magnetic resonance imaging (MRI) showed that the superior temporal and occipital cortex are involved in multisensory integration. Probabilistic fiber tracking based on diffusion-weighted MRI suggests that multisensory processing is supported by white matter connections between auditory cortex and the temporal and occipital lobe. Here, we present a combined functional MRI and probabilistic fiber tracking study that reveals multisensory processing mechanisms that remained undetected by either technique alone. Ten healthy participants passively observed visually presented lip or body movements, heard speech or body action sounds, or were exposed to a combination of both. Bimodal stimulation engaged a temporal-occipital brain network including the multisensory superior temporal sulcus (msSTS), the lateral superior temporal gyrus (lSTG), and the extrastriate body area (EBA). A region-of-interest (ROI) analysis showed multisensory interactions (e.g., subadditive responses to bimodal compared to unimodal stimuli) in the msSTS, the lSTG, and the EBA region. Moreover, sounds elicited responses in the medial occipital cortex. Probabilistic tracking revealed white matter tracts between the auditory cortex and the medial occipital cortex, the inferior occipital cortex (IOC), and the superior temporal sulcus (STS). However, STS terminations of auditory cortex tracts showed limited overlap with the msSTS region. Instead, msSTS was connected to primary sensory regions via intermediate nodes in the temporal and occipital cortex. Similarly, the lSTG and EBA regions showed limited direct white matter connections but instead were connected via intermediate nodes. Our results suggest that multisensory processing in the STS is mediated by separate brain areas that form a distinct network in the lateral temporal and inferior occipital cortex

A case report of metastasis of malignant mesothelioma to the oral gingiva

Introduction: Metastatic mesothelioma to the oral cavity arises from the pleura or peritoneum and distant hematogenous metastases are seen in more than half of cases but only a few cases are reported to the oral cavity Case: A 75 year old male suffering from metastatic mesothelioma presents an hyperplasia of the attached gingiva. Malignant mesothelioma is a rare tumour arising from pleura, pericardium or peritoneum. Conclusion: This article highlights the importance of biopsy and histopathological diagnosis of oral lesions especially in case of a malignant history

4D perfusion CT of prostate cancer for image-guided radiotherapy planning: A proof of concept study.

PURPOSE: Advanced forms of prostate cancer (PCa) radiotherapy with either external beam therapy or brachytherapy delivery techniques aim for a focal boost and thus require accurate lesion localization and lesion segmentation for subsequent treatment planning. This study prospectively evaluated dynamic contrast-enhanced computed tomography (DCE-CT) for the detection of prostate cancer lesions in the peripheral zone (PZ) using qualitative and quantitative image analysis compared to multiparametric magnet resonance imaging (mpMRI) of the prostate. METHODS: With local ethics committee approval, 14 patients (mean age, 67 years; range, 57-78 years; PSA, mean 8.1 ng/ml; range, 3.5-26.0) underwent DCE-CT, as well as mpMRI of the prostate, including standard T2, diffusion-weighted imaging (DWI), and DCE-MRI sequences followed by transrectal in-bore MRI-guided prostate biopsy. Maximum intensity projections (MIP) and DCE-CT perfusion parameters (CTP) were compared between healthy and malignant tissue. Two radiologists independently rated image quality and the tumor lesion delineation quality of PCa using a five-point ordinal scale. MIP and CTP were compared using visual grading characteristics (VGC) and receiver operating characteristics (ROC)/area under the curve (AUC) analysis. RESULTS: The PCa detection rate ranged between 57 to 79% for the two readers for DCE-CT and was 92% for DCE-MRI. DCE-CT perfusion parameters in PCa tissue in the PZ were significantly different compared to regular prostate tissue and benign lesions. Image quality and lesion visibility were comparable between DCE-CT and DCE-MRI (VGC: AUC 0.612 and 0.651, p>0.05). CONCLUSION: Our preliminary results suggest that it is feasible to use DCE-CT for identification and visualization, and subsequent segmentation for focal radiotherapy approaches to PCa

Differences in Fabry Cardiomyopathy Between Female and Male Patients Consequences for Diagnostic Assessment

ObjectivesWe hypothesized that Fabry cardiomyopathy in female patients might differ substantially from that in male patients and sought to prove this hypothesis in a large cohort consisting of 104 patients with Fabry disease.BackgroundFabry cardiomyopathy in male patients is characterized by left ventricular (LV) hypertrophy, impaired myocardial function, and subsequent progressive myocardial fibrosis. In contrast, the occurrence of these 3 cardiomyopathic hallmarks in female patients remains unknown.MethodsIn 104 patients (58 females, age 42 ± 16 years; 46 males, age 42 ± 13 years) with genetically proven Fabry disease, LV hypertrophy, regional myocardial deformation and myocardial fibrosis were assessed by standard echocardiography, strain rate imaging, and cardiac magnetic resonance (CMR) imaging–guided late enhancement (LE).ResultsIn men, end-diastolic left ventricular wall thickness (LVWT) ranged from 6 to 19.5 mm (LV mass CMR 55 to 200 g/m2), and LE was never seen with LVWT <12 mm (LV mass <99 g/m2). In contrast in female patients, LVWT ranged from 5 to 15.5 mm, LV mass ranged from 39 to 146 g/m2, and LE was already detectable with an LVWT of 9 mm (LV mass 56 g/m2). When LV mass was examined in CMR, LE was detected in 23% of the female patients without hypertrophy (n = 9), whereas LE was never seen in male patients with normal LV mass. LE was always associated with low systolic strain rate, but the severity of impairment was independent of LVWT in female patients (lateral strain rate in patients with LV hypertrophy with LE −0.7 ± 0.2 s−1; patients without LV hypertrophy with LE −0.8 ± 0.2 s−1; p = 0.45).ConclusionsIn contrast to male patients, the loss of myocardial function and the development of fibrosis do not necessarily require myocardial hypertrophy in female patients with Fabry disease. Thus, in contrast to actual recommendations, initial cardiac staging and monitoring should be based on LV hypertrophy and on replacement fibrosis in female patients with Fabry disease

Chest CT in patients after lung transplantation: A retrospective analysis to evaluate impact on image quality and radiation dose using spectral filtration tin-filtered imaging.

OBJECTIVES: The purpose of this study was to investigate the impact of a 150kV spectral filtration chest imaging protocol (Sn150kVp) combined with advanced modeled iterative reconstruction (ADMIRE) on radiation dose and image quality in patients after lung-transplantation. METHODS: This study included 102 patients who had unenhanced chest-CT examinations available on both, a second-generation dual-source CT (DSCT) using standard protocol (100kVp, filtered-back-projection) and, on a third-generation DSCT using Sn150kVp protocol with ADMIRE. Signal-to-noise-ratio (SNR) was measured in 6 standardized regions. A 5-point Likert scale was used to evaluate subjective image quality. Radiation metrics were compared. RESULTS: The mean time interval between the two acquisitions was 1.1±0.7 years. Mean-volume-CT-dose-index, dose-length-product and effective dose were significantly lower for Sn150kVp protocol (2.1±0.5mGy;72.6±16.9mGy*cm;1.3±0.3mSv) compared to 100kVp protocol (6.2±1.8mGy;203.6±55.6mGy*cm;3.7±1.0mSv) (p<0.001), equaling a 65% dose reduction. All studies were considered of diagnostic quality. SNR measured in lung tissue, air inside trachea, vertebral body and air outside the body was significantly higher in 100kVp protocol compared to Sn150kVp protocol (12.5±2.7vs.9.6±1.5;17.4±3.6vs.11.8±1.8;0.7±0.3vs.0.4±0.2;25.2±6.9vs.14.9±3.3;p<0.001). SNR measured in muscle tissue was significantly higher in Sn150kVp protocol (3.2±0.9vs.2.6±1.0;p<0.001). For SNR measured in descending aorta there was a trend towards higher values for Sn150kVp protocol (2.8±0.6 vs. 2.7±0.9;p = 0.3). Overall SNR was significantly higher in 100kVp protocol (5.0±4.0vs.4.0±4.0;p<0.001). On subjective analysis both protocols achieved a median Likert rating of 1 (25th-75th-percentile:1-1;p = 0.122). Interobserver agreement was good (intraclass correlation coefficient = 0.73). CONCLUSIONS: Combined use of 150kVp tin-filtered chest CT protocol with ADMIRE allows for significant dose reduction while maintaining highly diagnostic image quality in the follow up after lung transplantation when compared to a standard chest CT protocol using filtered back projection

Zweiter Fortschrittsbericht wirtschaftswissenschaftlicher Forschungsinstitute über die wirtschaftliche Entwicklung in Ostdeutschland.

Auch im Sommer 2003 kann die Entwicklung in der ostdeutschen Wirtschaft niemanden zufrieden stellen. Zusätzlich zu allen Diskussionen um Möglichkeiten einer Belebung der Wachstumsdynamik in ganz Deutschland stellt sich deswegen die Frage, wie die Politik dem Aufbau Ost neuen Schwung geben kann. Diese Frage stellt sich umso dringender, weil die finanzpolitischen Schwierigkeiten Deutschlands die Spielräume für finanziell kostspielige Programme für die neuen Länder stark einengen. Wichtige Bestandteile der Wirtschaftspolitik für Ostdeutschland waren in den letzten Jahren die spezifische Wirtschaftsförderung (insbesondere die Investitionsförderung), für die wegen ihrer Befristung wie auch wegen EU-rechtlicher Restriktionen nach Nachfolgelösungen gesucht wird, sowie die Aktive Arbeitsmarktpolitik, die im Zuge der allgemeinen Arbeitsmarktreformen ebenfalls auf den Prüfstand gestellt worden ist. In Anbetracht der anstehenden Entscheidungen über die weitere Strategie für den Aufbau Ost hat der Bundesminister der Finanzen die mit dem so genannten Fortschrittsbericht betrauten Forschungsinstitute – das Deutsche Institut für Wirtschaftsforschung Berlin (DIW), das Institut für Arbeitsmarkt- und Berufsforschung (IAB), das Institut für Weltwirtschaft an der Universität Kiel (IfW), das Institut für Wirtschaftsforschung Halle (IWH) und das Zentrum für Europäische Wirtschaftsforschung (ZEW) – deshalb gebeten, diese beiden Politikbereiche einer näheren Analyse zu unterziehen und darauf aufbauend wirtschaftspolitische Schlussfolgerungen abzuleiten. Darüber hinaus wurden als weitere Schwerpunkte der Arbeit eine regional differenzierte Analyse der Infrastrukturausstattung in den neuen Ländern, eine Untersuchung der technologischen Leistungsfähigkeit der ostdeutschen Wirtschaft und eine Analyse der finanzpolitischen Situation der ostdeutschen Länder und Gemeinden vereinbart.Wirtschaftliche Anpassung; Wirtschaftspolitik; Wirtschaftspolitische Wirkungsanalyse; Deutschland;

Zweiter Fortschrittsbericht wirtschaftswissenschaftlicher Forschungsinstitute über die wirtschaftliche Entwicklung in Ostdeutschland

Auch im Sommer 2003 kann die Entwicklung in der ostdeutschen Wirtschaft niemanden zufrieden stellen. Zusätzlich zu allen Diskussionen um Möglichkeiten einer Belebung der Wachstumsdynamik in ganz Deutschland stellt sich deswegen die Frage, wie die Politik dem Aufbau Ost neuen Schwung geben kann. Diese Frage stellt sich umso dringender, weil die finanzpolitischen Schwierigkeiten Deutschlands die Spielräume für finanziell kostspielige Programme für die neuen Länder stark einengen. Wichtige Bestandteile der Wirtschaftspolitik für Ostdeutschland waren in den letzten Jahren die spezifische Wirtschaftsförderung (insbesondere die Investitionsförderung), für die wegen ihrer Befristung wie auch wegen EU-rechtlicher Restriktionen nach Nachfolgelösungen gesucht wird, sowie die Aktive Arbeitsmarktpolitik, die im Zuge der allgemeinen Arbeitsmarktreformen ebenfalls auf den Prüfstand gestellt worden ist. In Anbetracht der anstehenden Entscheidungen über die weitere Strategie für den Aufbau Ost hat der Bundesminister der Finanzen die mit dem so genannten Fortschrittsbericht betrauten Forschungsinstitute – das Deutsche Institut für Wirtschaftsforschung Berlin (DIW), das Institut für Arbeitsmarkt- und Berufsforschung (IAB), das Institut für Weltwirtschaft an der Universität Kiel (IfW), das Institut für Wirtschaftsforschung Halle (IWH) und das Zentrum für Europäische Wirtschaftsforschung (ZEW) – deshalb gebeten, diese beiden Politikbereiche einer näheren Analyse zu unterziehen und darauf aufbauend wirtschaftspolitische Schlussfolgerungen abzuleiten. Darüber hinaus wurden als weitere Schwerpunkte der Arbeit eine regional differenzierte Analyse der Infrastrukturausstattung in den neuen Ländern, eine Untersuchung der technologischen Leistungsfähigkeit der ostdeutschen Wirtschaft und eine Analyse der finanzpolitischen Situation der ostdeutschen Länder und Gemeinden vereinbart. --

Within-host evolution of SARS-CoV-2 in an immunosuppressed COVID-19 patient as a source of immune escape variants.

The origin of SARS-CoV-2 variants of concern remains unclear. Here, we test whether intra-host virus evolution during persistent infections could be a contributing factor by characterizing the long-term SARS-CoV-2 infection dynamics in an immunosuppressed kidney transplant recipient. Applying RT-qPCR and next-generation sequencing (NGS) of sequential respiratory specimens, we identify several mutations in the viral genome late in infection. We demonstrate that a late viral isolate exhibiting genome mutations similar to those found in variants of concern first identified in UK, South Africa, and Brazil, can escape neutralization by COVID-19 antisera. Moreover, infection of susceptible mice with this patient's escape variant elicits protective immunity against re-infection with either the parental virus and the escape variant, as well as high neutralization titers against the alpha and beta SARS-CoV-2 variants, B.1.1.7 and B.1.351, demonstrating a considerable immune control against such variants of concern. Upon lowering immunosuppressive treatment, the patient generated spike-specific neutralizing antibodies and resolved the infection. Our results suggest that immunocompromised patients could be a source for the emergence of potentially harmful SARS-CoV-2 variants

Intranasal delivery of bone marrow derived mesenchymal stem cells, macrophages, and microglia to the brain in mouse models of Alzheimer's and Parkinson's disease

In view of the rapid preclinical development of cell-based therapies for neurodegenerative disorders, traumatic brain injury, and tumors, the safe and efficient delivery and targeting of therapeutic cells to the central nervous system is critical for maintaining therapeutic efficacy and safety in the respective disease models. Our previous data demonstrated therapeutically efficacious and targeted delivery of mesenchymal stem cells (MSCs) to the brain in the rat 6-hydroxydopamine model of Parkinson’s disease (PD). The present study examined delivery of bone marrow derived MSCs, macrophages, and microglia to the brain in a transgenic model of PD ((Thy1)-h[A30P] αS) and an APP/PS1 model of Alzheimer’s disease (AD) via intranasal application (INA). INA of microglia in naïve BL/6 mice led to targeted and effective delivery of cells to the brain. Quantitative PCR analysis of eGFP DNA showed that the brain contained the highest amount of eGFP-microglia (up to 2.1x104) after INA of 1x106 cells, while the total amount of cells detected in peripheral organs did not exceed 3.4x103. Seven days after INA, MSCs expressing eGFP were detected in the olfactory bulb (OB), cortex, amygdala, striatum, hippocampus, cerebellum, and brainstem of (Thy1)-h[A30P] αS transgenic mice, showing predominant distribution within the OB and brainstem. INA of eGFP-expressing macrophages in 13 month-old APP/PS1 mice led to delivery of cells to the OB, hippocampus, cortex, and cerebellum. Both, MSCs and macrophages contained Iba-1-positive population of small microglia-like cells and Iba-1-negative large rounded cells showing either intracellular Amyloid beta (macrophages in APP/PS1 model) or α-Synuclein (MSCs in (Thy1)-h[A30P] αS model) immunoreactivity. Here we show, for the first time, intranasal delivery of cells to the brain of transgenic PD and AD mouse models. Additional work is needed to determine the optimal dosage (single treatment regimen or repeated administrations) to achieve functional improvement in these mouse models with intranasal microglia/macrophages and MSCs