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Δευτέρα 12 Σεπτεμβρίου 2016

IJMS, Vol. 17, Pages 1531: Cancer Salivary Biomarkers for Tumours Distant to the Oral Cavity

The analysis of saliva as a diagnostic approach for systemic diseases was proposed just two decades ago, but recently great interest in the field has emerged because of its revolutionary potential as a liquid biopsy and its usefulness as a non-invasive sampling method. Multiple molecules isolated in saliva have been proposed as cancer biomarkers for diagnosis, prognosis, drug monitoring and pharmacogenetic studies. In this review, we focus on the current status of the salivary diagnostic biomarkers for different cancers distant to the oral cavity, noting their potential use in the clinic and their applicability in personalising cancer therapies.

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Proteomes, Vol. 4, Pages 28: “Omics”-Informed Drug and Biomarker Discovery: Opportunities, Challenges and Future Perspectives

The pharmaceutical industry faces unsustainable program failure despite significant increases in investment. Dwindling discovery pipelines, rapidly expanding R&D budgets and increasing regulatory control, predict significant gaps in the future drug markets. The cumulative duration of discovery from concept to commercialisation is unacceptably lengthy, and adds to the deepening crisis. Existing animal models predicting clinical translations are simplistic, highly reductionist and, therefore, not fit for purpose. The catastrophic consequences of ever-increasing attrition rates are most likely to be felt in the developing world, where resistance acquisition by killer diseases like malaria, tuberculosis and HIV have paced far ahead of new drug discovery. The coming of age of Omics-based applications makes available a formidable technological resource to further expand our knowledge of the complexities of human disease. The standardisation, analysis and comprehensive collation of the "data-heavy" outputs of these sciences are indeed challenging. A renewed focus on increasing reproducibility by understanding inherent biological, methodological, technical and analytical variables is crucial if reliable and useful inferences with potential for translation are to be achieved. The individual Omics sciences—genomics, transcriptomics, proteomics and metabolomics—have the singular advantage of being complimentary for cross validation, and together could potentially enable a much-needed systems biology perspective of the perturbations underlying disease processes. If current adverse trends are to be reversed, it is imperative that a shift in the R&D focus from speed to quality is achieved. In this review, we discuss the potential implications of recent Omics-based advances for the drug development process.

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Minerals, Vol. 6, Pages 94: Investigation of Platinum-Group Minerals (PGM) from Othrys Chromitites (Greece) Using Superpanning Concentrates

Platinum-group minerals were concentrated using superpanning from two composite chromitite samples, which were collected from two old mines within the Othrys ophiolite. This method allows for the recovery of a broad spectrum of these rare and fine-grained minerals, and helps to better identify them and interpret their origin. Major differences between the east and west Othrys ophiolites were determined, probably as a result of their different origin and evolution. Primary Os-, Ir-, and Ru-bearing platinum-group minerals (IPGM)-alloys and the Rh-, Pt- and Pd-bearing platinum-group minerals (PPGM) occur only in the east Othrys chromitite, indicating an evolution from initially low fS2 conditions at shallower mantle levels with the subsequent implication of a S-saturated ascending fluid. In contrast, the absence of primary IPGM-alloys in west Othrys chromitite indicates that S saturation had been attained. The presence of erlichmanite suggests that sulphur fugacity eventually increased significantly in both suites. Substantial fluctuations of a fluid phase, likely related to serpentinising fluids, modified the platinum-group minerals (PGM) assemblage of west Othrys, and resulted in a large diversity of secondary PGM minerals. The limited number of secondary species developed in the east Othrys indicate that secondary processes were also different in the two suites.

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IJMS, Vol. 17, Pages 1509: Testosterone-Mediated Endocrine Function and TH1/TH2 Cytokine Balance after Prenatal Exposure to Perfluorooctane Sulfonate: By Sex Status

Little information exists about the evaluation of potential developmental immunotoxicity induced by perfluorooctane sulfonate (PFOS), a synthetic persistent and increasingly ubiquitous environmental contaminant. To assess potential sex-specific impacts of PFOS on immunological health in the offspring, using male and female C57BL/6 mice, pups were evaluated for developmental immunotoxic effects after maternal oral exposure to PFOS (0.1, 1.0 and 5.0 mg PFOS/kg/day) during Gestational Days 1–17. Spontaneous TH1/TH2-type cytokines, serum levels of testosterone and estradiol were evaluated in F1 pups at four and eight weeks of age. The study showed that male pups were more sensitive to the effects of PFOS than female pups. At eight weeks of age, an imbalance in TH1/TH2-type cytokines with excess TH2 cytokines (IL-4) was found only in male pups. As for hormone levels, PFOS treatment in utero significantly decreased serum testosterone levels and increased estradiol levels only in male pups, and a significant interaction between sex and PFOS was observed for serum testosterone at both four weeks of age (pinteraction = 0.0049) and eight weeks of age (pinteraction = 0.0227) and for estradiol alternation at four weeks of age (pinteraction = 0.0351). In conclusion, testosterone-mediated endocrine function may be partially involved in the TH1/TH2 imbalance induced by PFOS, and these deficits are detectable among both young and adult mice and may affect males more than females.

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Applied Sciences, Vol. 6, Pages 257: Overview of 3D Micro- and Nanocoordinate Metrology at PTB

Improved metrological capabilities for three-dimensional (3D) measurements of various complex micro- and nanoparts are increasingly in demand. This paper gives an overview of the research activities carried out by the Physikalisch-Technische Bundesanstalt (PTB), the national metrology institute of Germany, to meet this demand. Examples of recent research advances in the development of instrumentation and calibration standards are presented. An ultra-precision nanopositioning and nanomeasuring machine (NMM) has been upgraded with regard to its mirror corner, interferometers and angle sensors, as well as its weight compensation, its electronic controller, its vibration damping stage and its instrument chamber. Its positioning noise has been greatly reduced, e.g., from 1σ = 0.52 nm to 1σ = 0.13 nm for the z-axis. The well-known tactile-optical fibre probe has been further improved with regard to its 3D measurement capability, isotropic probing stiffness and dual-sphere probing styli. A 3D atomic force microscope (AFM) and assembled cantilever probes (ACPs) have been developed which allow full 3D measurements of smaller features with sizes from a few micrometres down to tens of nanometres. In addition, several measurement standards for force, geometry, contour and microgear measurements have been introduced. A type of geometry calibration artefact, referred to as the "3D Aztec artefact", has been developed which applies wet-etched micro-pyramidal marks for defining reference coordinates in 3D space. Compared to conventional calibration artefacts, it has advantages such as a good surface quality, a well-defined geometry and cost-effective manufacturing. A task-specific micro-contour calibration standard has been further developed for ensuring the traceability of, e.g., high-precision optical measurements at microgeometries. A workpiece-like microgear standard embodying different gear geometries (modules ranging from 0.1 mm to 1 mm) has also been developed at the Physikalisch-Technische Bundesanstalt.

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Molecules, Vol. 21, Pages 1223: Synergistic Antipseudomonal Effects of Synthetic Peptide AMP38 and Carbapenems

The aim was to explore the antimicrobial activity of a synthetic peptide (AMP38) and its synergy with imipenem against imipenem-resistant Pseudomonas aeruginosa. The main mechanism of imipenem resistance is the loss or alteration of protein OprD. Time-kill and minimal biofilm eradication concentration (MBEC) determinations were carried out by using clinical imipenem-resistant strains. AMP38 was markedly synergistic with imipenem when determined in imipenem-resistant P. aeruginosa. MBEC obtained for the combination of AMP38 and imipenem was of 62.5 μg/mL, whereas the MBEC of each antimicrobial separately was 500 μg/mL. AMP38 should be regarded as a promising antimicrobial to fight MDR P. aeruginosa infections. Moreover, killing effect and antibiofilm activity of AMP38 plus imipenem was much higher than that of colistin plus imipenem.

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Computers, Vol. 5, Pages 19: Fractal Aspects in Classical Parallel Computing

In this paper, we prove that many parallel communication topologies and several parallel algorithms have fractal properties, which leads to the idea that there is a strong connection between the classical parallel computing and a plausible computing on a fractal medium. Furthermore, we show that some parallel algorithms are suitable for incursive and hyperincursive computation, which links parallel computing to quantum computing and a possible fractal computing.

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IJMS, Vol. 17, Pages 1532: A Protocol to Enhance INS1E and MIN6 Functionality—The Use of Theophylline

In vitro research in the field of type I diabetes is frequently limited by the availability of a functional model for islets of Langerhans. This method shows that by the addition of theophylline to the glucose buffers, mouse insulinoma MIN6 and rat insulinoma INS1E pseudo-islets can serve as a model for islets of Langerhans for in vitro research. The effect of theophylline is dose- and cell line-dependent, resulting in a minimal stimulation index of five followed by a rapid return to baseline insulin secretion by reducing glucose concentrations after a first high glucose stimulation. This protocol solves issues concerning in vitro research for type I diabetes as donors and the availability of primary islets of Langerhans are limited. To avoid the limitations of using human donor material, cell lines represent a valid alternative. Many different β cell lines have been reported, but the lack of reproducible responsiveness to glucose stimulation remains a challenge.

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Molecules, Vol. 21, Pages 1132: Antidiarrheal Thymol Derivatives from Ageratina glabrata. Structure and Absolute Configuration of 10-Benzoyloxy-8,9-epoxy-6-hydroxythymol Isobutyrate

Chemical investigation of the leaves from Ageratina glabrata yielded four new thymol derivatives, namely: 10-benzoyloxy-8,9-dehydro-6-hydroxythymol isobutyrate (4), 10-benzoyloxy-8,9-dehydrothymol (5), 10-benzoyloxythymol (6) and 10-benzoyloxy-6,8-dihydroxy-9-isobutyryl-oxythymol (7). In addition, (8S)-10-benzoyloxy-8,9-epoxy-6-hydroxythymol isobutyrate (1), together with other two already known thymol derivatives identified as 10-benzoyloxy-8,9-epoxy-6-methoxythymol isobutyrate (2) and 10-benzoyloxy-8,9-epoxythymol isobutyrate (3) were also obtained. In this paper, we report the structures and complete assignments of the 1H and 13C-NMR data of compounds 1–7, and the absolute configuration for compound 1, unambiguously established by single crystal X-ray diffraction, and evaluation of the Flack parameter. The in vitro antiprotozoal assay showed that compound 1 and its derivative 1a were the most potent antiamoebic and antigiardial compounds. Both compounds showed selectivity and good antiamoebic activity comparable to emetine and metronidazole, respectively, two antiprotozoal drugs used as positive controls. In relation to anti-propulsive effect, compound 1 and 1a showed inhibitory activity, with activities comparable to quercetin and compound 9, two natural antipropulsive compounds used as positive controls. These data suggest that compound 1 may play an important role in antidiarrheal properties of Ageratina glabrata.

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Improving and accelerating the differentiation and functional maturation of human stem cell-derived neurons: role of extracellular calcium and GABA

Abstract

Neurons differentiated from pluripotent stem cells using established neural culture conditions often exhibit functional deficits. Recently, we have developed enhanced media which both synchronise the neurogenesis of pluripotent stem cell-derived neural progenitors and accelerate their functional maturation; together these media are termed SynaptoJuice. This pair of media are pro-synaptogenic and generate authentic, mature synaptic networks of connected forebrain neurons from a variety of induced pluripotent and embryonic stem cell lines. Such enhanced rate and extent of synchronised maturation of pluripotent stem cell-derived neural progenitor cells generates neurons which are characterised by a relatively hyperpolarized resting membrane potential, higher spontaneous and induced action potential activity, enhanced synaptic activity, more complete development of a mature inhibitory GABAA receptor phenotype and faster production of electrical network activity when compared to standard differentiation media. This entire process - from pre-patterned neural progenitor to active neuron - takes 3 weeks or less, making it an ideal platform for drug discovery and disease modelling in the fields of human neurodegenerative and neuropsychiatric disorders, such as Huntington's disease, Parkinson's disease, Alzheimer's disease or Schizophrenia.

This article is protected by copyright. All rights reserved



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Processes, Vol. 4, Pages 32: Origins and Evolution of Inorganic-Based and MOF-Based Mixed-Matrix Membranes for Gas Separations

Gas separation for industrial, energy, and environmental applications requires low energy consumption and small footprint technology to minimize operating and capital costs for the processing of large volumes of gases. Among the separation methods currently being used, like distillation, amine scrubbing, and pressure and temperature swing adsorption, membrane-based gas separation has the potential to meet these demands. The key component, the membrane, must then be engineered to allow for high gas flux, high selectivity, and chemical and mechanical stability at the operating conditions of feed composition, pressure, and temperature. Among the new type of membranes studied that show promising results are the inorganic-based and the metal-organic framework-based mixed-matrix membranes (MOF-MMMs). A MOF is a unique material that offers the possibility of tuning the porosity of a membrane by introducing diffusional channels and forming a compatible interface with the polymer. This review details the origins of these membranes and their evolution since the first inorganic/polymer and MOF/polymer MMMs were reported in the open literature. The most significant advancements made in terms of materials, properties, and testing conditions are described in a chronological fashion.

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Marine Drugs, Vol. 14, Pages 167: An Overview of the Medical Applications of Marine Skeletal Matrix Proteins

In recent years, the medicinal potential of marine organisms has attracted increasing attention. This is due to their immense diversity and adaptation to unique ecological niches that has led to vast physiological and biochemical diversification. Among these organisms, marine calcifiers are an abundant source of novel proteins and chemical entities that can be used for drug discovery. Studies of the skeletal organic matrix proteins of marine calcifiers have focused on biomedical applications such as the identification of growth inducing proteins that can be used for bone regeneration, for example, 2/4 bone morphogenic proteins (BMP). Although a few reports on the functions of proteins derived from marine calcifiers can be found in the literature, marine calcifiers themselves remain an untapped source of proteins for the development of innovative pharmaceuticals. Following an overview of the current knowledge of skeletal organic matrix proteins from marine calcifiers, this review will focus on various aspects of marine skeletal protein research including sources, biosynthesis, structures, and possible strategies for chemical or physical modification. Special attention will be given to potential medical applications and recent discoveries of skeletal proteins and polysaccharides with biologically appealing characteristics. In addition, I will introduce an effective protocol for sample preparation and protein purification that includes isolation technology for biopolymers (of both soluble and insoluble organic matrices) from coralline algae. These algae are a widespread but poorly studied group of shallow marine calcifiers that have great potential for marine drug discovery.

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Metals, Vol. 6, Pages 223: Deformation Characteristic and Constitutive Modeling of 2707 Hyper Duplex Stainless Steel under Hot Compression

Hot deformation behavior and microstructure evolution of 2707 hyper duplex stainless steel (HDSS) were investigated through hot compression tests in the temperature range of 900–1250 °C and strain rate range of 0.01–10 s−1. The results showed that the flow behavior strongly depended on strain rate and temperature, and flow stress increased with increasing strain rate and decreasing temperature. At lower temperatures, many precipitates appeared in ferrite and distributed along the deformation direction, which could restrain processing of discontinuous dynamic recrystallization (DRX) because of pinning grain boundaries. When the temperature increased to 1150 °C, the leading softening behaviors were dynamic recovery (DRV) in ferrite and discontinuous DRX in austenite. When the temperature reached 1250 °C, softening behavior was mainly DRV in ferrite. The increase of strain rate was conducive to the occurrence of discontinuous DRX in austenite. A constitutive equation at peak strain was established and the results indicated that 2707 HDSS had a higher Q value (569.279 kJ·mol−1) than other traditional duplex stainless steels due to higher content of Cr, Mo, Ni, and N. Constitutive modeling considering strain was developed to model the hot deformation behavior of 2707 HDSS more accurately, and the correlation coefficient and average absolute relative error were 0.992 and 5.22%, respectively.

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Catalysts, Vol. 6, Pages 141: Olefin Hydroborations with Diamidocarbene–BH3 Adducts at Room Temperature

An isolable N,N'-diamidocarbene (DAC) was previously shown to promote the B–H bond activation of various BH3 complexes. The resultant DAC–BH3 adducts facilitated olefin hydroborations under mild conditions and in the absence of exogenous initiators. The substrate scope for such transformations was further explored and is described herein. While organoboranes were obtained in quantitative yields from various terminal and internal olefins, use of the latter substrates resulted in intramolecular ring-expansion of the newly formed DAC–borane adducts.

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Marine Drugs, Vol. 14, Pages 166: R-Phycoerythrin Induces SGC-7901 Apoptosis by Arresting Cell Cycle at S Phase

R-Phycoerythrin (R-PE), one of the chemical constituents of red algae, could produce singlet oxygen upon excitation with the appropriate radiation and possibly be used in photodynamic therapy (PDT) for cancer. Documents reported that R-PE could inhibit cell proliferation in HepG2 and A549 cells, which was significative for cancer therapy. This is due to the fact that R-PE could kill cancer cells directly as well as by PDT. However, little is known about the cytotoxicity of R-PE to the SGC-7901 cell. In this study, it has been found that R-PE could inhibit SGC-7901 proliferation and induce cell apoptosis, which was achieved by arresting the SGC-7901 cell at S phase. CyclinA, CDK2 and CDC25A are proteins associated with the S phase, and it was found that R-PE could increase the expression of cyclin A protein and decrease the expression of CDK2 and CDC25A proteins. Thus, it was concluded that R-PE reduced the CDK2 protein activated through decreasing the CDC25A factor, which reduced the formation of Cyclin-CDK complex. The reduction of Cyclin-CDK complex made the SGC-7901 cells arrest at the S phase. Therefore, R-PE induced apoptosis by arresting the SGC-7901 cell at S phase was successful, which was achieved by the expression of the CDC25A protein, which reduced the CDK2 protein actived and the formation of Cyclin-CDK complex.

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Energies, Vol. 9, Pages 739: Impact of Rural Grid-Connected Photovoltaic Generation Systems on Power Quality

Photovoltaic (PV) generation systems have been increasingly used to generate electricity from renewable sources, attracting a growing interest. Recently, grid connected PV micro-generation facilities in individual homes have increased due to governmental policies as well as greater attention by industry. As low voltage (LV) distribution systems were built to make energy flow in one direction, the power feed-in of PV generation in rural low-voltage grids can influence power quality (PQ) as well as facility operation and reliability. This paper presents results on PQ analysis of a real PV generation facility connected to a rural low-voltage grid. Voltage fluctuations and voltage harmonic contents were observed. Statistical analysis shows a negative impact on PQ produced by this PV facility and also that only a small fraction of the energy available during a sunny day is converted, provoking losses of revenue and forcing the converter to work in an undesirable operating mode. We discuss the disturbances imposed upon the grid and their outcome regarding technical and economic viability of the PV system, as well as possible solutions. A low-voltage grid strengthening has been suggested and implemented. After that a new PQ analysis shows an improvement in the impact upon PQ, making this facility economically viable.

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Viral and host responses after stopping long-term nucleos(t)ide analogue therapy in HBeAg negative chronic hepatitis B

The Journal of Infectious Diseases

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Safety profile of biologic drugs in the treatment of inflammatory bowel diseases: A systematic review and network meta-analysis of randomized controlled trials

Clinical Drug Investigation

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Perineural bupivacaine injection reduces inguinodynia after inguinal hernia repair

Surgery

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Proton pump inhibitor monotherapy and the risk of cardiovascular events in patients with gastro-esophageal reflux disease: A meta-analysis

Neurogastroenterology & Motility

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Association between bone mineral density and nonalcoholic fatty liver disease in Korean adults

Journal of Endocrinological Investigation

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Predictors of treatment requirement in HBeAg-negative chronic hepatitis B patients with persistently normal ALT and high serum HBV-DNA levels

International Journal of Infectious Diseases

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Twenty-five years of advocacy for patients with gastroparesis: Support group therapy and patient reported outcome tool development

BMC Gastroenterology

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The impact on endoscopic resource utilization after a targeted intervention for cost-minimization of EGD and colonoscopy

The American Journal of Gastroenterology

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Impact of split completeness on future liver remnant hypertrophy in associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in hepatocellular carcinoma: Complete-ALPPS versus partial-ALPPS

Surgery

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Impact of country of birth on age at the time of diagnosis of hepatocellular carcinoma in the United States

Cancer

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Outcomes following repeat hepatic resection for recurrent metastatic colorectal cancer: A population-based study

The American Journal of Surgery

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Mast cells are associated with the onset and progression of celiac disease

The Journal of Allergy and Clinical Immunology

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FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab for metastatic colorectal cancer (FIRE-3): A post-hoc analysis of tumour dynamics in the final wild-type subgroup of this randomised double-blind phase 3 trial

The Lancet Oncology

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Early primary biliary cholangitis is characterised by brain abnormalities on cerebral magnetic resonance imaging

Alimentary Pharmacology and Therapeutics

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Distinct pathways of pathogenesis of intraductal oncocytic papillary neoplasms and intraductal papillary mucinous neoplasms of the pancreas

Virchows Archiv

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Histopathological findings of extra-ileal manifestations at initial diagnosis of Crohns disease-related ileitis

Virchows Archiv

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Laparoscopic azygoportal disconnection with and without splenectomy for portal hypertension

International Journal of Surgery

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Assessment of Vitamin D status in a group of Egyptian children with non alcoholic fatty liver disease (multicenter study)

Nutrition & Metabolism

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Metabolic dysfunction, obesity, and survival among patients with early-stage colorectal cancer

Journal of Clinical Oncology

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Improved detection of recurrent hepatocellular carcinomas in arterial phase with CAIPIRINHA-Dixon-TWIST-volumetric interpolated breath-hold examination

Investigative Radiology

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Logistics, Vol. 1, Pages 1: Logistics Is about Competitiveness and More

Stripped to its basics, logistics is about capturing competitive advantage and creating customer value, not just optimizing costs.[...]

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Remote Sensing, Vol. 8, Pages 751: Compact Polarimetric SAR Ship Detection with m-δ Decomposition Using Visual Attention Model

A few previous studies have illustrated the potentials of compact polarimetric Synthetic Aperture Radar (CP SAR) in ship detection. In this paper, we design a ship detection algorithm of CP SAR from the perspective of computer vision. A ship detection algorithm using the pulsed cosine transform (PCT) visual attention model is proposed to suppress background clutter and highlight conspicuous ship targets. It is the first time that a visual attention model is introduced to CP SAR application. The proposed algorithm is a quick and complete framework for practical use. Polarimetric features—the relative phase δ and volume scattering component—are extracted from m-δ decomposition to eliminate false alarms and modify the PCT model. The constant false alarm rate (CFAR) algorithm based on lognormal distribution is adopted to detect ship targets, after a clutter distribution fitting procedure of the modified saliency map. The proposed method is then tested on three simulated circular-transmit-linear-receive (CTLR) mode images, which covering East Sea of China. Compared with the detection results of SPAN and the saliency map with only single-channel amplitude, the proposed method achieves the highest detection rates and the lowest misidentification rate and highest figure of merit, proving the effectiveness of polarimetric information of compact polarimetric SAR ship detection and the enhancement from the visual attention model.

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Remote Sensing, Vol. 8, Pages 750: Impact of Sensor Zenith Angle on MOD10A1 Data Reliability and Modification of Snow Cover Data for the Tarim River Basin

Snow in the mountainous watersheds of the Tarim River Basin is the primary source of water for western China. The Snow Cover Daily L3 Global 500-m Grid (MOD10A1) remote sensing dataset has proven extremely valuable for monitoring the changing snow cover patterns over large spatial areas; however, inherent uncertainty associated with large sensor zenith angles (SZAs) has called its reliability into question. Comparative analysis that utilized a paired-date difference method for parameters such as snow cover frequency, snow cover percentage, and normalized difference snow index (NDSI) has shown that overestimation of snow cover in the Tarim River Basin correlates with high values of SZA. Hence, such overestimation was associated with an increase in the NDSI, attributable to the change in reflectance between Band 4 and Band 6 imagery. A maximum threshold value of SZA of 22.37° was used alongside a multiday refilling method to modify the MOD10A1 dataset to produce a new daily snow cover map of the Tarim River Basin, spanning a 10-year period. A comparison of benchmark results of snow cover classification produced by the HJ-1A/B satellite revealed an increase in the overall accuracy of up to 4%, confirming the usefulness of our modified MOD10A1 data.

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Remote Sensing, Vol. 8, Pages 745: A Scale-Driven Change Detection Method Incorporating Uncertainty Analysis for Remote Sensing Images

Change detection (CD) based on remote sensing images plays an important role in Earth observation. However, the CD accuracy is usually affected by sunlight and atmospheric conditions and sensor calibration. In this study, a scale-driven CD method incorporating uncertainty analysis is proposed to increase CD accuracy. First, two temporal images are stacked and segmented into multiscale segmentation maps. Then, a pixel-based change map with memberships belonging to changed and unchanged parts is obtained by fuzzy c-means clustering. Finally, based on the Dempster-Shafer evidence theory, the proposed scale-driven CD method incorporating uncertainty analysis is performed on the multiscale segmentation maps and the pixel-based change map. Two experiments were carried out on Landsat-7 Enhanced Thematic Mapper Plus (ETM+) and SPOT 5 data sets. The ratio of total errors can be reduced to 4.0% and 7.5% for the ETM+ and SPOT 5 data sets in this study, respectively. Moreover, the proposed approach outperforms some state-of-the-art CD methods and provides an effective solution for CD.

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Forests, Vol. 7, Pages 201: How Time since Forest Fire Affects Stand Structure, Soil Physical-Chemical Properties and Soil CO2 Efflux in Hemiboreal Scots Pine Forest Fire Chronosequence?

We compared the changes in aboveground biomass and initial recovery of C pools and CO2 efflux following fire disturbances in Scots pine (Pinus sylvesteris L.) stands with different time since stand-replacing fire. The study areas are located in hemiboreal vegetation zone, in north-western Estonia, in Vihterpalu. Six areas where the last fire occurred in the year 1837, 1940, 1951, 1982, 1997, and 2008 were chosen for the study. Our results show that forest fire has a substantial effect on the C content in the top soil layer, but not in the mineral soil layers. Soil respiration showed a chronological response to the time since the forest fire and the values were lowest in the area where the fire was in the year 2008. The respiration values also followed seasonal pattern being highest in August and lowest in May and November. The CO2 effluxes were lowest on the newly burned area through the entire growing season. There was also a positive correlation between soil temperature and soil respiration values in our study areas.

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JFB, Vol. 7, Pages 25: A Smart pH-Responsive Three Components Luminescent Hydrogel

In this study, we report a novel three-component luminescent hydrogel, which is composed of amino acid derivatives (N,N′-di valine-3,4,9,10-perylenetetracarboxylic acid, NVPD), riboflavin (RF), and melamine (MM). The three-component hydrogel is attributed to multiple hydrogen bonds and the strong π-π stacking interaction between these molecules. Based on the strong hydrogen bonding of the gelator, when the reversible process between the gel and the solution take places it changes the pH of the system from 6.1 to 10.6. In addition, green fluorescence could be the emissive of the hydrogel under 498 nm and the conversion process of the aggregation state repeated reversibly by altering the value of ambient pH. This pH-responsive luminescent gel may display potential for use in nano pH sensors.

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Remote Sensing, Vol. 8, Pages 749: A Novel Tri-Training Technique for Semi-Supervised Classification of Hyperspectral Images Based on Diversity Measurement

This paper introduces a novel semi-supervised tri-training classification algorithm based on diversity measurement for hyperspectral imagery. In this algorithm, three measures of diversity, i.e., double-fault measure, disagreement metric and correlation coefficient, are applied to select the optimal classifier combination from different classifiers, e.g., support vector machine (SVM), multinomial logistic regression (MLR), extreme learning machine (ELM) and k-nearest neighbor (KNN). Then, unlabeled samples are selected using an active learning (AL) method, and consistent results of any other two classifiers combined with a spatial neighborhood information extraction strategy are employed to predict their labels. Moreover, a multi-scale homogeneity (MSH) method is utilized to refine the classification result with the highest accuracy in the classifier combination, generating the final classification result. Experiments on three real hyperspectral data indicate that the proposed approach can effectively improve classification performance.

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JMSE, Vol. 4, Pages 59: Dynamics of a Marine Turbine for Deep Ocean Currents

For most of the ocean currents, such as the Kuroshio at east Taiwan, the Gulf Stream at east Florida and the Agulhas Current at southeast Africa, the depth of the seabed is generally deeper than one hundred meters, some waters of which can even reach one thousand meters. In such deep waters, the design of the turbine, as well as the anchoring system shall have special features so that existing ocean engineering technologies can be applied and the engineering cost can be lowered. Thus, as regards design, in addition to the analysis of the interaction between turbine and current, priority shall also be given to the design of the anchoring system of the turbine. To address the concerns, the authors propose an ocean turbine featured as follows: (1) it can be anchored in deep waters with a single cable; (2) it can generate high power in a current of moderate flow speed while producing low drag; (3) it can be self-balanced against current disturbance; (4) it is shrouded to enhance power efficiency; (5) the dynamic variations due to the interaction between the turbine and current are small. All of these features are confirmed with the computational results, leading to a detailed design of the turbine structure. If the easy-to-install high-efficiency shrouded turbines, having the capability to self-balance and requiring minimum maintenance effort, are successfully developed, the power supply pressure in Taiwan can be greatly alleviated. The Kuroshio was chosen as the typical current for the present dynamic analysis because, firstly, the flow characteristics of Kuroshio are similar to those of other large-scale currents mentioned above, and secondly, the data of Kuroshio are highly available to us so that a thorough analysis can be done.

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Viruses, Vol. 8, Pages 246: On the Selective Packaging of Genomic RNA by HIV-1

Like other retroviruses, human immunodeficiency virus type 1 (HIV-1) selectively packages genomic RNA (gRNA) during virus assembly. However, in the absence of the gRNA, cellular messenger RNAs (mRNAs) are packaged. While the gRNA is selected because of its cis-acting packaging signal, the mechanism of this selection is not understood. The affinity of Gag (the viral structural protein) for cellular RNAs at physiological ionic strength is not much higher than that for the gRNA. However, binding to the gRNA is more salt-resistant, implying that it has a higher non-electrostatic component. We have previously studied the spacer 1 (SP1) region of Gag and showed that it can undergo a concentration-dependent conformational transition. We proposed that this transition represents the first step in assembly, i.e., the conversion of Gag to an assembly-ready state. To explain selective packaging of gRNA, we suggest here that binding of Gag to gRNA, with its high non-electrostatic component, triggers this conversion more readily than binding to other RNAs; thus we predict that a Gag–gRNA complex will nucleate particle assembly more efficiently than other Gag–RNA complexes. New data shows that among cellular mRNAs, those with long 3′-untranslated regions (UTR) are selectively packaged. It seems plausible that the 3′-UTR, a stretch of RNA not occupied by ribosomes, offers a favorable binding site for Gag.

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Toxins, Vol. 8, Pages 267: Bioactivation and Regioselectivity of Pig Cytochrome P450 3A29 towards Aflatoxin B1

Due to unavoidable contaminations in feedstuff, pigs are easily exposed to aflatoxin B1 (AFB1) and suffer from poisoning, thus the poisoned products potentially affect human health. Heretofore, the metabolic process of AFB1 in pigs remains to be clarified, especially the principal cytochrome P450 oxidases responsible for its activation. In this study, we cloned CYP3A29 from pig liver and expressed it in Escherichia coli, and its activity has been confirmed with the typical P450 CO-reduced spectral characteristic and nifedipine-oxidizing activity. The reconstituted membrane incubation proved that the recombinant CYP3A29 was able to oxidize AFB1 to form AFB1-exo-8,9-epoxide in vitro. The structural basis for the regioselective epoxidation of AFB1 by CYP3A29 was further addressed. The T309A mutation significantly decreased the production of AFBO, whereas F304A exhibited an enhanced activation towards AFB1. In agreement with the mutagenesis study, the molecular docking simulation suggested that Thr309 played a significant role in stabilization of AFB1 binding in the active center through a hydrogen bond. In addition, the bulk phenyl group of Phe304 potentially imposed steric hindrance on the binding of AFB1. Our study demonstrates the bioactivation of pig CYP3A29 towards AFB1 in vitro, and provides the insight for understanding regioselectivity of CYP3A29 to AFB1.

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Evidence for feasibility of fetal trophoblastic cell-based noninvasive prenatal testing

Abstract

Objective

The goal was to develop methods for detection of chromosomal and subchromosomal abnormalities in fetal cells in the mother's circulation at 10-16 weeks gestation using analysis by array comparative genomic hybridization (CGH) and/or next-generation sequencing (NGS).

Method

Nucleated cells from 30 ml of blood collected at 10-16 weeks gestation were separated from red cells by density fractionation and then immunostained to identify cytokeratin positive and CD45 negative trophoblasts. Individual cells were picked and subjected to whole genome amplification, genotyping, and analysis by array CGH and NGS.

Results

Fetal cells were recovered from most samples as documented by Y chromosome PCR, short tandem repeat analysis, array CGH, and NGS including over 30 normal male cells, one 47,XXY cell from an affected fetus, one trisomy 18 cell from an affected fetus, nine cells from a trisomy 21 case, three normal and one trisomy 13 cells from a case with confined placental mosaicism, and two chromosome 15 deletion cells from a case known by CVS to have a 2.7 Mb de novo deletion.

Conclusion

We believe that this is the first report of using array CGH and NGS whole genome sequencing to detect chromosomal abnormalities in fetal trophoblastic cells from maternal blood. This article is protected by copyright. All rights reserved.



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Markers associated with Alzheimer’s and Parkinson’s diseases are present in Mexico City children chronically exposed to concentrations of fine particulate matter PM2.5 above the current EPA USA standards

Mexico City (MC) children have lifetime exposures to concentrations of air pollutants above the current USA standards, including fine particulate matter (PM 2.5). Metropolitan Mexico City is an example of extreme urban growth and serious environmental pollution including high exposures to PM 2.5, ozone, polycyclic aromatic hydrocarbons (PAH), metals, endotoxins, tobacco smog, open waste dumps, highly polluting heavy duty trucks (not subjected to any pollution controls), etc., resulting in millions of children involuntarily exposed to harmful air neurotoxic substances every day since conception.

The results of this study including the significantly low concentrations of Aβ 1-42 and Brain-derived neurotrophic factor (BDNF) in MC children versus controls, suggests that major changes in key neural proteins playing major roles in neurotoxicity, cell survival, axonal and dendritic growth, and synaptic plasticity are evolving in urban MC children. Decreased levels of BDNF are associated with the development of obesity, depression, mood disorders, and neurodegeneration. Interestingly, Mexico City children increased their levels of total prion protein (TPrP) with cumulative PM2.5 up to 5 μg/m3 and then decreased, regardless of cumulative value or age. The low values of this key protein are likely detrimental given its protective effects against oxidative stress and its role in cell signaling, metal interactions, memory, myelin maintenance, axonal growth and neuronal development. Total synuclein showed an increment in childhood years related to cumulated PM2.5, followed by a decrease after age 12 years, while the abnormal synuclein associated with Parkinson's disease exhibited a tendency to increase with cumulated PM2.5.

Mexico City children, teens, and young adults have shown a key marker of Alzheimer disease (AD): hyperphosphorylated tau along significant brain and intrathecal neuroinflammation, dysregulated immune responses, breakdown of epithelial and endothelial barriers, damage to the neurovascular unit, and brain accumulation of metals associated with combustion. Moreover, seemingly healthy children in Mexico City have olfaction deficits, dysregulation of feeding regulatory hormones, deficiencies in attention and short-term memory, and below-average scores in Verbal and Full Scale IQ compared to low air pollution children.

"Researchers are very concerned young Mexico City urbanites exhibit evidence of spectral markers of neurodegeneration that are often seen in adults with mild cognitive impairment, in Alzheimer patients and in mouse models of Alzheimer's disease" said Dr. Lilian Calderón-Garcidueňas.

"Our concern about Parkinson's disease is also increased when we observed children and teens with early autonomic dysfunction and in brainstem materials, extensive accumulation of α- synuclein in key nuclei including auditory nuclei and the dorsal nucleus of the vagus" said authors.

"These results add to growing data from our laboratory and others, suggesting urban residents with chronic high exposures to ozone and fine particulate matter have a higher risk for developing Alzheimer's disease (Jung et al., J Alzheimers Dis, 44, 573-584, 2015) and the potential key role of environmental magnetite nanoparticles in the brains of Mexico City residents (Maher et al., Proc Natl Acad Sci U S A, early edition) commented Dr. Calderón-Garcidueňas.

Air pollution is a serious public health issue and exposures to concentrations of air pollutants at or above the current standards have been clearly linked to neuroinflammation and neurodegeneration.

There is an urgent need for studying air pollution interactions impacting children's brains and their responses, which could provide new avenues for Alzheimer's and Parkinson's disease prevention.

The authors concluded: "We have a 50-year window of opportunity between the time urban children experience the detrimental effects we are describing here and when they will present with mild cognitive impairment, dementia, tremor or all of the above. Our efforts should be aimed to identify and mitigate environmental factors influencing the early development of neurodegenerative diseases and to neuroprotect high risk children. Unfortunately, to date there has been no support for studying the detrimental neurodegenerative effects of air pollution on the pediatric brain."

# # #

Contact:
Lilian Calderón-Garcidueňas, MA, MD, PhD
Biomedical Sciences
University of Montana
+1 406 243 4785
lilian.calderon-garciduenas@umontana.edu

NOTES FOR EDITORS
"Cerebrospinal fluid biomarkers in highly exposed PM2.5 urbanites: The risk of Alzheimer's and Parkinson's diseases in young Mexico City residents" by Lilian Calderón-Garcidueňas, José Avila-Ramírez, Ana Calderón-Garcidueñas, Tonatiuh González-Heredia, Hilda Acuña-Ayala, Chih-kai Chao, Charles Thompson, Rubén Ruiz- Ramos, Victor Cortés-González, Luz Martínez-Martínez, Mario Alberto García-Pérez, Jacques Reis, Partha S. Mukherjee, Ricardo Torres-Jardón, Ingolf Lachmann, J Alzheimers Dis 54, 597-613, 2016.

ABOUT THE JOURNAL OF ALZHEIMER'S DISEASE (JAD)
The Journal of Alzheimer's Disease is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer's disease. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. Published by IOS Press.



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Efficacy and Safety of Crocus Sativus L in Patients with Mild Cognitive Impairment: One Year Single-Blind Randomized, with Parallel Groups, Clinical Trial

Scientists from the Aristotle University of Thessaloniki (AUTH), the Greek Association of Alzheimer's Disease and Related Disorders (GAADRD) and the Centre for Research and Technology Hellas/Information Technologies Institute (CERTH/ITI) have succeeded in making the shift to MCI therapy via robust natural remedies that can be used in order to forestall cognitive deterioration. In an article published in the Journal of Alzheimer's Disease, the researchers have indicated that 0,125 gr/ per day lead to better cognitive performance after 12 months as revealed in neuropsychological assessment, ERP response, and 3 Tesla MRI. P300 latency was measured by a HD-EEG [EGI 300 Geodesic EEG system (GES 300) using a 256-channel HydroCel Geodesic Sensor Net (HCGSN)]. A small volume increase on the left inferior temporal gyrus, an area close to medial temporal lobe (MTL) and hippocampus, was found in experimental group. Thus, this study highlighted how Crocus can change brain activation, striatal volume of specific brain regions, neuropsychological performance and cognitive processing in aMCI patients whereas control group exhibited worse performance after 12 months. Consequently, patients with MCI can hopefully have better cognitive functioning by taking Crocus Sativus L. on a daily basis.

It is widely known that no conventional or alternative therapy is currently available and approved to treat MCI patients. Current therapeutic strategies for cognitive impairment in AD, is symptomatic with cholinesterase inhibitors (ChEIs) including donepezil, rivastigmine, galantamine, and the N-methyl-D-aspartate (NMDA) receptor antagonist memantine. The discovery of new natural compounds with neuroactive properties for the management of Neurodegenerative diseases (NDs) has gained much attention recently. Since no drug treatment is available to prevent the development of NDs, studies have shown that diet or plant-based extracts with antioxidant properties may have beneficial effects on improving brain function in NDs.

Nevertheless, preclinical and clinical pharmacological studies have demonstrated that Crocus sativus crude extracts and purified chemicals of it have anti-tumor effects, radical scavenging activity, anti-nociceptive and anti-inflammatory properties, inhibitory activity on Amyloid beta aggregation, reduce atherosclerosis and hepatic damage, counteract hyperlipidemia, protect from myocardial injury, display antihypertensive action, and finally it is safe and effective in mild to moderate AD as revealed from this study. More specifically, crocins and crocetin (molecules of Crocus sativus L.) have a wide range of activities including antioxidant effects, neuroprotective activities in memory impairment and antioxidant capacities. Also, crocin acts on NMDA receptors and on tracheal muscles β2-adrenoceptors, with a possible inhibitory effect on histamine (H1) receptors. More specifically, in vitro and in silico studies also suggest that crocetin can inhibit acetylcholinesterase, a main AD medicinal target.

Our study revealed in all measures we used better performance of treatment group compared with control group in the second assessment after 12 months of follow-up. Until today there is no other study which has proved that any kind of medication can be considered as an effective solution for patients with MCI. The same organizations are also focused on developing other novel pharmaceutical natural compounds that respond to a number of clinical needs in the effort against neurocognitive disorders.

*****

NOTES FOR EDITORS:
Efficacy and Safety of Crocus sativus L. in Patients with Mild Cognitive Impairment: One Year Single-Blind Randomized, with Parallel Groups, Clinical Trial. Tsolaki M, Karathanasi E, Lazarou I, Dovas K, Verykouki E, Karacostas A, Georgiadis K, Tsolaki A, Adam K, Kompatsiaris I, Sinakos Z. J Alzheimers Dis. 2016 Jul 27;54(1):129-33. doi: 10.3233/JAD-160304. PMID: 27472878

Contact-Principal Investigator:
Magda Tsolaki
Professor of 3rd Department of Neurology, Aristotle University of Thessaloniki, Greece
Chair of Greek Federation of Alzheimer's disease in Greece
Scientific Director of Daily Alzheimer's centers in Thessaloniki, Greece
E-mail: tsolakim1@gmail.com
Tel: +306942918933, +302310234239
Fax: +30 2313 307332

About the Aristotle University of Thessaloniki (AUTH)
The Aristotle University of Thessaloniki is the largest university in Greece. It comprises 7 faculties that consist of 33 schools, 5 faculties that consist of one school each, as well as 4 independent schools. About 81,500 students study at the Aristotle University (72,140 in undergraduate programs and 8,360 in postgraduate programs). There are 2,150 faculty members: 739 professors, 435 associate professors, 634 assistant professors, and 342 lecturers. There are also 11 teaching assistants, 58 research fellows, 248 members of the Special Laboratory Teaching Personnel (S.L.T.P.), as well as 15 foreign language teachers and 4 foreign instructors. Faculty members are also assisted by 213 members of the Special Technical Laboratory Personnel (S.T.L.P.).

The Aristotle University of Thessaloniki conducts research projects, participates in European research programs, cooperates with international institutions and organizations and attracts outstanding researchers from within Greece and abroad. The Aristotle University supports research projects in a wide variety of disciplines related to the environment (natural and built), computing, new technologies and nanotechnology, telecommunications, industrial technologies, transport, biotechnology, biomedicine and health, agriculture, forestry and fishery, education and language, history and archaeology, social studies and economics.

About the Greek Association of Alzheimer's disease and Related Disorders (GAADRD)
The Greek Association of Alzheimer's Disease and Related Disorders is a non-profit organization that was founded in 1995 by relatives of patients suffering from Alzheimer's disease, doctors of all specialties (mainly neurologists and psychiatrists) and other experts (such as psychologists, social workers, physiotherapists, etc.) who deal with the problems caused by this disease and other types of dementia. The Association operates 2 day centers in Thessaloniki and has over 4.000 members. It is a member of Alzheimer Europe and Alzheimer's disease International (ADI) and has successfully participated in various national and European research projects producing new scientific knowledge and innovative interventions for cognitive disorders.

The aim of the Association is to offer information and advice concerning the care of patients with cognitive disorders and provide services for patients and their families. It also strives to offer help and support to caregivers in order to reduce the social, economic and emotional burden deriving from the long term care of people suffering from dementia. Lastly, the Association attempts to publicize the social needs of the affected population and inform the public on issues related to dementia and cognitive disorders in general.

About the Information Technologies Institute (ITI)-Centre for Research and Technology Hellas (CERTH)
The Information Technologies Institute, formerly Informatics and Telematics Institute, was established in 1998 in Thessaloniki as a non-profit research organization under the auspices of the General Secretariat of Research and Technology (GSRT) of the Greek Ministry of Development. Since 2000, ITI has joined the Centre for Research and Technology Hellas (CERTH). The main objective of the Institute is to be a research institution of excellence, identifying promising fields for the future and creating an environment that will allow the transfer of basic, applied and technological research in the growth of the digital economy of the 21st century. CERTH/ITI has developed spheres of excellence and critical mass in research and technology in several strategically important fields in a number of areas: Image and Signal Processing, Computer Vision, Human Computer Interaction, Virtual and Augmented Reality, Artificial Intelligence, Security and Surveillance, Biomedicine – Bioinformatics, Robotics, ICT for Environment Monitoring, Geosciences and Remote Sensing, Social Network Analysis, Networks and Communications, Cultural and Educational Technology.

About Journal of Alzheimer's disease (JAD)
The Journal of Alzheimer's Disease is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer's disease. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. Groundbreaking research that has appeared in the journal includes novel therapeutic targets, mechanisms of disease and clinical trial outcomes. The Journal of Alzheimer's Disease has an Impact Factor of 4.151 according to Thomson Reuters' 2014 Journal Citation Reports. The Journal is published by IOS Press.

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References
[1] Pitsikas N (2015) The effect of Crocus sativus L. and its constituents on memory: basic studies and clinical applications. Evid Based Complement Alternat Med 2015, 926284.
[2] Howe AS, Bani-Fatemi A, De Luca V (2014) The clinical utility of the auditory P300 latency subcomponent event-related potential in preclinical diagnosis of patients with mild cognitive impairment and Alzheimer's disease. Brain Cogn 86, 64–74.



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Midlife physical activity is associated with better cognition in old age

The association was studied first in all individuals of the cohort, and then by comparing later cognition in pairs where one twin was more physically active than the other.

Increasing the volume of physical activity was not, however, associated with increased memory-protecting benefits. Instead, quite a moderate amount of physical activity was found to be sufficient for memory-protecting benefits, and only the most inactive group of twins stood out with a significantly higher risk for cognitive impairment.

Overall, the study shows that moderately vigorous physical activity, meaning more strenuous than walking, is associated with better cognition after an average of 25 years.

This finding is in accordance with earlier animal model studies, which have shown that physical activity increases the amount of growth factors in the brain and improves synaptic plasticity.

The prevalence of dementia has increased with aging populations both in Finland and globally. Although the incidence of dementia seems to have decreased in less senior generations, the total prevalence of dementia is still expected to rise. No cure for dementia exists, but during the last decade research has produced an abundance of new information on dementia prevention. The traditional vascular risk factors (elevated blood pressure, hypercholesterolemia, obesity, diabetes and lack of exercise) have also been associated with dementia risk. However, few long-term, high-quality, follow-up studies on physical activity and cognition have been published, and it has remained unclear what type and amount of exercise is needed to safeguard cognition.

The study was conducted by scientists at the universities of Helsinki, Jyväskylä and Turku. The twins provided information on physical activity through questionnaire surveys from 1975 and 1981 (mean age in 1981: 49 years), while cognition was assessed by validated telephone interviews conducted between 1999 and 2015.

An early online version of this paper detailing the findings has been published. The full article is scheduled for publication in the 54(4) issue of the Journal of Alzheimer's Disease (Journal of Alzheimer's Disease 2016; 54(4), DOI 10.3233/JAD-160377).

Iso-Markku P, Waller K, Vuoksimaa E, Heikkilä K, Rinne J, Kaprio J, Kujala UM (2016) Midlife Physical Activity and Cognition Later in Life: A Prospective Twin Study. J Alzheimers Dis, DOI 10.3233/JAD-160377

Further information:
Researcher, M.D. Paula Iso-Markku, paula.iso-markku@helsinki.fi, tel. +358 50 428 4611
Professor Urho Kujala, urho.m.kujala@jyu.fi, tel. +358 40 805 3567



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