'Public Health', 'Social Solidarity' and a modern Greek tragedy....

First paragraph: We are writing these lines in November 2018; 6 years after the Greek Ministry of Public Health and Social Solidary first issued Health Regulation No GY/39A, which gave the Greek police the power to detain drug users, amongst other groups, for forced HIV testing and compulsory hospitalisation and treatment (where deemed 'appropriate'). The Health Regulation was issued amidst what was deemed a public health emergency. For the first time, the number of new HIV transmissions among people who inject drugs had exceeded the number of new cases reported among men who have sex with men. During the first seven months of 2011, new transmissions among people who inject drugs had increased more than tenfold. By 2012, approximately half of all newly reported HIV transmissions were linked to injecting drug use.Output Type: Blog Pos

Spatiotemporal Identification of Cell Divisions Using Symmetry Properties in Time-Lapse Phase Contrast Microscopy

A variety of biological and pharmaceutical studies, such as for anti-cancer drugs, require the quantification of cell responses over long periods of time. This is performed with time-lapse video microscopy that gives a long sequence of frames. For this purpose, phase contrast imaging is commonly used since it is minimally invasive. The cell responses of interest in this study are the mitotic cell divisions. Their manual measurements are tedious, subjective, and restrictive. This study introduces an automated method for these measurements. The method starts with preprocessing for restoration and reconstruction of the phase contrast time-lapse sequences. The data are first restored from intensity non-uniformities. Subsequently, the circular symmetry of the contour of the mitotic cells in phase contrast images is used by applying a Circle Hough Transform (CHT) to reconstruct the entire cells. The CHT is also enhanced with the ability to “vote” exclusively towards the center of curvature. The CHT image sequence is then registered for misplacements between successive frames. The sequence is subsequently processed to detect cell centroids in individual frames and use them as starting points to form spatiotemporal trajectories of cells along the positive as well as along the negative time directions, that is, anti-causally. The connectivities of different trajectories enhanced by the symmetry of the trajectories of the daughter cells provide as topological by-products the events of cell divisions together with the corresponding entries into mitoses as well as exits from cytokineses. The experiments use several experimental video sequences from three different cell lines with many cells undergoing mitoses and divisions. The quantitative validations of the results of the processing demonstrate the high performance and efficiency of the method

Reliability of a risk-factor questionnaire for osteoporosis: a primary care survey study with dual energy x-ray absorptiometry ground truth

(1) Purpose: Predisposing factors to osteoporosis (OP) as well as dual-source x-ray densitometry (DXA) steer therapeutic decisions by determining the FRAX index. This study examines the reliability of a standard risk factor questionnaire in OP-screening. (2) Methods: n = 553 eligible questionnaires encompassed 24 OP-predisposing factors. Reliability was assessed using DXA as a gold standard. Multiple logistic regression and Spearman’s correlations, as well as the confounding influence of age and body mass index, were analyzed in SPSS (IBM Corporation, Armonk, NY, USA). (3) Results: Our study revealed low patient self-awareness regarding OP and its risk factors. One out of every four patients reported a positive history for osteoporosis not confirmed by DXA. The extraordinarily high incidence of rheumatoid arthritis and thyroid disorders likely reflect confusion with other diseases or health anxiety. FRAX-determining risk factors such as malnutrition, liver insufficiency, prior fracture without trauma, and glucocorticoid therapy did not correlate with increased OP incidence, altogether demonstrating how inaccurate survey information could influence therapeutic decisions on osteoporosis. (4) Conclusions: Contradictive results and a low level of patient self-awareness suggest a high degree of uncertainty and low reliability of the current OP risk factor survey

Phosphorylation of the actin binding protein Drebrin at S647 and is regulated by neuronal activity and PTEN

Defects in actin dynamics affect activity-dependent modulation of synaptic transmission and neuronal plasticity, and can cause cognitive impairment. A salient candidate actin-binding protein linking synaptic dysfunction to cognitive deficits is Drebrin (DBN). However, the specific mode of how DBN is regulated at the central synapse is largely unknown. In this study we identify and characterize the interaction of the PTEN tumor suppressor with DBN. Our results demonstrate that PTEN binds DBN and that this interaction results in the dephosphorylation of a site present in the DBN C-terminus - serine 647. PTEN and pS647-DBN segregate into distinct and complimentary compartments in neurons, supporting the idea that PTEN negatively regulates DBN phosphorylation at this site. We further demonstrate that neuronal activity increases phosphorylation of DBN at S647 in hippocampal neurons in vitro and in ex vivo hippocampus slices exhibiting seizure activity, potentially by inducing rapid dissociation of the PTEN:DBN complex. Our results identify a novel mechanism by which PTEN is required to maintain DBN phosphorylation at dynamic range and signifies an unusual regulation of an actin-binding protein linked to cognitive decline and degenerative conditions at the CNS synapse

Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment

Sickness behavior and cognitive dysfunction occur frequently by unknown mechanisms in virus-infected individuals with malignancies treated with type I interferons (IFNs) and in patients with autoimmune disorders. We found that during sickness behavior, single-stranded RNA viruses, double-stranded RNA ligands, and IFNs shared pathways involving engagement of melanoma differentiation-associated protein 5 (MDA5), retinoic acid-inducible gene 1 (RIG-I), and mitochondrial antiviral signaling protein (MAVS), and subsequently induced IFN responses specifically in brain endothelia and epithelia of mice. Behavioral alterations were specifically dependent on brain endothelial and epithelial IFN receptor chain 1 (IFNAR). Using gene profiling, we identified that the endothelia-derived chemokine ligand CXCL10 mediated behavioral changes through impairment of synaptic plasticity. These results identified brain endothelial and epithelial cells as natural gatekeepers for virus-induced sickness behavior, demonstrated tissue specific IFNAR engagement, and established the CXCL10-CXCR3 axis as target for the treatment of behavioral changes during virus infection and type I IFN therapy

Einfluss der aktivierten Mikroglia-Zellen auf neuronales Überleben und Erregbarkeit

Microglia are the central nervous system´s (CNS) resident macrophages. The myeloid progenitors that determine the microglial lineage colonize the CNS in the early embryonic life and serve thereafter the local innate immunity. In the immune privileged CNS, microglial innate immune functions are constitutively suppressed (‘resting’). Activation of microglial innate immune functions, such as direct cytotoxicity, antigen presentation, sequestration and stimulation of lymphocytes and phagocytosis, has been associated with reduction of the ‘resting/surveying’ ramified morphology and somatic transition to a round, ‘ameboid’ shape. Microglial activation is a pathologic hallmark in many CNS diseases and a common finding in in vitro neurodegeneration models. However, the causality underlying the correlation between microglial activation and neurodegeneration is currently debated. In this study we used the organotypic hippocampal slice culture as a model to investigate the impact of microglial activation on neuronal function and survival. After exposure of organotypic slices to the purified bacterial endotoxin lipopolysaccharide (LPS), for 72 hours, the microglial activation was quantified by assaying the supernatant for nitrite production, as well as for the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). By applying anti-Iba1 immunohistochemistry and quantitative morphological methods (stereology and Neurolucida® tracings) we additionally described the microglial population in terms of size and ramification pattern. Standard histochemical and immunohistochemical staining (toluidine blue, NeuN) in combination with the specific neurodegeneration marker Fluoro-Jade B® were used to quantify neurodegeneration. The impact of microglial activation on neuronal function was assessed in the CA1 hippocampal subregion by extracellular electrophysiological measurements of the spontaneous (multiunit activity and local field potential) and evoked field activity (input-output properties and short88 term plasticity). Moreover, by studying stimulation- evoked potassium ([K+]o) transients with ion-sensitive microelectrodes we probed the homeostatic capacity of the local neuro-glial network. Our results show that the LPS-triggered microglial activation did not result to neurodegeneration. Furthermore, minimal changes in the electrophysiological field activity and [K+]o transients argue against a fundamental perturbation of the neuronal and astroglial function. The absence of neuronal death after LPS exposure in organotypic slice cultures, in sharp contrast to the severe degeneration occurring in vivo and in primary cultures, suggests that microglial activation is not necessarily neurotoxic and toxicity may occur in a context-dependent manner. With the present study we have established a model to further investigate the factors that may link microglial activation with neurotoxicity.Die Mikroglia-Zellen sind die Makrophagen des zentralen Nervensystem. Deren Myeloid Vorläuferzellen wandern während der frühen Embryogenese in das zentrale Nervensystem (ZNS) ein und vermitteln dort die angeborene Immunität, die im ZNS unter normalen Bedingungen konstitutiv unterdrückt ist. Demzufolge, befinden sich die Mikrogliazellen in einem „Ruhezustand. Der Übergang zum aktiven Status der Mikrogliazellen, ausgelöst z.B. durch Zelltoxizität, Antigenpräsentation, Lymphozytenstimulation oder Phagozytose führt zu einer bemerkenswerten Veränderung der Zellmorphologie: Die weitverzweigte Erscheinung der ruhenden/beobachtenden Zellen wird durch ein eher „amöboides“ Erscheinungsbild des Zellkörpers ersetzt. Dieser Aktivierungsprozess ist nicht nur ein auffälliges Erscheinungsbild vieler pathologischer Zustände des ZNS, sondern lässt sich auch in diversen in vitro Modellen neurodegenerativer Krankheiten beobachten. Dies legt einen kausalen Zusammenhang zwischen Aktivierung und pathologischer Manifestation nahe, ohne dass diese allerdings zweifelsfrei nachgewiesen werden konnte. Zu diesem Zweck wurde in der vorliegenden Arbeit der Einfluss von Mikrogliazellenaktivierung auf neuronale Zellen und ihr Überleben untersucht. Inkubation mit dem bakteriellen Endotoxin (Lipopolysaccharide, LPS) für 72 Stunden führte zu einer verlässlichen und reproduzierbaren Aktivierung der Mikrogliazellen. Dies konnte durch Quantifizierung des Nitritgehalts im Überstand, der entzündungsfördernden Interleukine IL-6 und des Tumornecrosis factors α (TNF-α) belegt werden. Eine detaillierte Analyse der Mikroglia- Morphologie wurde durch immunohistochemische und stereologische Methoden durchgeführt, mit einem Schwerpunkt auf Zellkörpergröße und Verzweigungsgrad. Diese Parameter, die den Aktivierungsgrad der Mikrogliazellen charakterisieren, wurden mit verschiedenen, histo- und immunzytochemischen Markern (toluidine blue, NeuN) des Zellüberlebens und solchen spezifisch für Neurodegeneration (Fluoro-Jade B®) korreliert. Unabhängig vom Überleben der Nervenzellen, wurde auch deren Funktion nach Mikrogliaaktivierung untersucht. Dazu wurden in der hippokampalen CA1 Region extrazelluläre elektrophysiologische Ableitungen durchgeführt, die Aufschlüsse über spontanes und evoziertes Verhalten (multiunit activity, evoked and spontaneous local field potential, Kurzzeitplastizität) geben. Darüber hinaus wurde auch die homeostatische Regulation der extrazellulären Kaliumkonzentration mit ionensensitiven Elektroden charakterisiert. In dieser Studie wurden neurodegenerative Vorgänge nicht von LPS-induzierter Mikrogliaaktivierung beeinflusst. Darüber hinaus wiesen auch die elektrophysiologischen und ionensensitiven Messungen nicht auf eine grundlegende Veränderung der neuronalen und astrogliären Funktionen hin, sondern enthüllten nur geringfügige Veränderungen. Diese Resultate widersprechen bisherigen Erkenntnissen aus in vivo und Primärkulturexperimenten. Eine mögliche Interpretation der Daten stellte daher keinen zwangsläufigen kausalen Zusammenhang zwischen Mikrogliazellenaktivierung und Neurotoxizität her; ein solcher Zusammenhang könnte aber im hohen Maße kontextabhängig und nicht kanonisch sein. Um solche kontextabhängigen Zusammenhänge aufzuklären, ist das in dieser Arbeit etablierte experimentelle Modell hervorragend geeignet

Quantitative Assessment of Breast-Tumor Stiffness Using Shear-Wave Elastography Histograms

Purpose: Shear-wave elastography (SWE) measures tissue elasticity using ultrasound waves. This study proposes a histogram-based SWE analysis to improve breast malignancy detection. Methods: N = 22/32 (patients/tumors) benign and n = 51/64 malignant breast tumors with histological ground truth. Colored SWE heatmaps were adjusted to a 0–180 kPa scale. Normalized, 250-binned RGB histograms were used as image descriptors based on skewness and area under curve (AUC). The histogram method was compared to conventional SWE metrics, such as (1) the qualitative 5-point scale classification and (2) average stiffness (SWEavg)/maximal tumor stiffness (SWEmax) within the tumor B-mode boundaries. Results: The SWEavg and SWEmax did not discriminate malignant lesions in this database, p > 0.05, rank sum test. RGB histograms, however, differed between malignant and benign tumors, p < 0.001, Kolmogorov–Smirnoff test. The AUC analysis of histograms revealed the reduction of soft-tissue components as a significant SWE biomarker (p = 0.03, rank sum). The diagnostic accuracy of the suggested method is still low (Se = 0.30 for Se = 0.90) and a subject for improvement in future studies. Conclusions: Histogram-based SWE quantitation improved the diagnostic accuracy for malignancy compared to conventional average SWE metrics. The sensitivity is a subject for improvement in future studies

Neuroscience Scaffolded by Informatics: A Raging Interdisciplinary Field

Following breakthrough achievements in molecular neurosciences, the current decade witnesses a trend toward interdisciplinary and multimodal development. Supplementation of neurosciences with tools from computer science solidifies previous knowledge and sets the ground for new research on “big data” and new hypothesis-free experimental models. In this Special Issue, we set the focus on informatics-supported interdisciplinary neuroscience accomplishments symmetrically combining wet-lab and clinical routines. Video-tracking and automated mitosis detection in vitro, the macromolecular modeling of kinesin motion, and the unsupervised classification of the brain’s macrophage activation status share a common denominator: they are energized by machine and deep learning. Essential clinical neuroscience questions such as the estimated risk of brain aneurysm rupture and the surgical outcome of facial nerve transplantation are addressed in this issue as well. Precise and rapid evaluation of complex clinical data by deep learning and data mining dives deep to reveal symmetrical and asymmetrical features beyond the abilities of human perception or the limits of linear algebraic modeling. This editorial opts to motivate researchers from the wet lab, computer science, and clinical environments to join forces in reshaping scientific platforms, share and converge high-quality data on public platforms, and use informatics to facilitate interdisciplinary information exchange

Neuroscience Scaffolded by Informatics: A Raging Interdisciplinary Field

Following breakthrough achievements in molecular neurosciences, the current decade witnesses a trend toward interdisciplinary and multimodal development. Supplementation of neurosciences with tools from computer science solidifies previous knowledge and sets the ground for new research on “big data” and new hypothesis-free experimental models. In this Special Issue, we set the focus on informatics-supported interdisciplinary neuroscience accomplishments symmetrically combining wet-lab and clinical routines. Video-tracking and automated mitosis detection in vitro, the macromolecular modeling of kinesin motion, and the unsupervised classification of the brain’s macrophage activation status share a common denominator: they are energized by machine and deep learning. Essential clinical neuroscience questions such as the estimated risk of brain aneurysm rupture and the surgical outcome of facial nerve transplantation are addressed in this issue as well. Precise and rapid evaluation of complex clinical data by deep learning and data mining dives deep to reveal symmetrical and asymmetrical features beyond the abilities of human perception or the limits of linear algebraic modeling. This editorial opts to motivate researchers from the wet lab, computer science, and clinical environments to join forces in reshaping scientific platforms, share and converge high-quality data on public platforms, and use informatics to facilitate interdisciplinary information exchange