A novel procedure for the detection of specific DNA sequences has been developed. This procedure is based on the already known method employing PCR with appropriate primers and a sequence-specific DNA probe labeled with the fluorescent agent 6-carboxylfluorescein (FAM) at the 5′ end and the fluorescence quencher BHQ-1 (black hole quencher) at the 3′ end. However, instead of the detection of the fluorescence signal with the use of real-time PCR cyclers, fluorescence/luminescence spectrometers or fluorescence polarization readers, as in all previously-reported procedures, we propose visual observation of the fluorescence under UV light directly in the reaction tube. An example for the specific detection of the Shiga toxin-producing Escherichia coli (STEC) strains, by detecting Shiga toxin genes, is demonstrated. This method appears to be specific, simple, rapid and cost effective. It may be suitable for use in research laboratories, as well as in diagnostic units of medical institutions, even those equipped only with a thermocycler and a UV transilluminator, particularly if rapid identification of a pathogen is required.
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Παρασκευή 13 Νοεμβρίου 2015
Toxins, Vol. 7, Pages 4745-4757: A Simple and Rapid Procedure for the Detection of Genes Encoding Shiga Toxins and Other Specific DNA Sequences
Viruses, Vol. 7, Pages 5889-5901: Harnessing the Power of Onco-Immunotherapy with Checkpoint Inhibitors
Oncolytic viruses represent a diverse class of replication competent viruses that curtail tumor growth. These viruses, through their natural ability or through genetic modifications, can selectively replicate within tumor cells and induce cell death while leaving normal cells intact. Apart from the direct oncolytic activity, these viruses mediate tumor cell death via the induction of innate and adaptive immune responses. The field of oncolytic viruses has seen substantial advancement with the progression of numerous oncolytic viruses in various phases of clinical trials. Tumors employ a plethora of mechanisms to establish growth and subsequently metastasize. These include evasion of immune surveillance by inducing up-regulation of checkpoint proteins which function to abrogate T cell effector functions. Currently, antibodies blocking checkpoint proteins such as anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1) have been approved to treat cancer and shown to impart durable clinical responses. These antibodies typically need pre-existing active immune tumor microenvironment to establish durable clinical outcomes and not every patient responds to these therapies. This review provides an overview of published pre-clinical studies demonstrating superior therapeutic efficacy of combining oncolytic viruses with checkpoint blockade compared to monotherapies. These studies provide compelling evidence that oncolytic therapy can be potentiated by coupling it with checkpoint therapies.
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Toxins, Vol. 7, Pages 4730-4744: Vitamin D3 and Monomethyl Fumarate Enhance Natural Killer Cell Lysis of Dendritic Cells and Ameliorate the Clinical Score in Mice Suffering from Experimental Autoimmune Encephalomyelitis
Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell mediated inflammatory demyelinating disease that is induced in mice by administration of peptides derived from myelin proteins. We developed EAE in SJL mice by administration of PLP139–151 peptide. The effect of treating these mice with 1α,25-Dihydroxyvitamin D3 (vitamin D3), or with monomethyl fumarate (MMF) was then examined. We observed that both vitamin D3 and MMF inhibited and/or prevented EAE in these mice. These findings were corroborated with isolating natural killer (NK) cells from vitamin D3-treated or MMF-treated EAE mice that lysed immature or mature dendritic cells. The results support and extend other findings indicating that an important mechanism of action for drugs used to treat multiple sclerosis (MS) is to enhance NK cell lysis of dendritic cells.
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Systems, Vol. 3, Pages 287-308: Exploring Tradeoffs in Demand-Side and Supply-Side Management of Urban Water Resources Using Agent-Based Modeling and Evolutionary Computation
Urban water supply systems may be managed through supply-side and demand-side strategies, which focus on water source expansion and demand reductions, respectively. Supply-side strategies bear infrastructure and energy costs, while demand-side strategies bear costs of implementation and inconvenience to consumers. To evaluate the performance of demand-side strategies, the participation and water use adaptations of consumers should be simulated. In this study, a Complex Adaptive Systems (CAS) framework is developed to simulate consumer agents that change their consumption to affect the withdrawal from the water supply system, which, in turn influences operational policies and long-term resource planning. Agent-based models are encoded to represent consumers and a policy maker agent and are coupled with water resources system simulation models. The CAS framework is coupled with an evolutionary computation-based multi-objective methodology to explore tradeoffs in cost, inconvenience to consumers, and environmental impacts for both supply-side and demand-side strategies. Decisions are identified to specify storage levels in a reservoir that trigger: (1) increases in the volume of water pumped through inter-basin transfers from an external reservoir; and (2) drought stages, which restrict the volume of water that is allowed for residential outdoor uses. The proposed methodology is demonstrated for Arlington, Texas, water supply system to identify non-dominated strategies for an historic drought decade. Results demonstrate that pumping costs associated with maximizing environmental reliability exceed pumping costs associated with minimizing restrictions on consumer water use.
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Membranes, Vol. 5, Pages 702-721: Lipid Diffusion in Supported Lipid Bilayers: A Comparisonbetween Line-Scanning Fluorescence Correlation Spectroscopyand Single-Particle Tracking
Diffusion in lipid membranes is an essential component of many cellular process and fluorescence a method of choice to study membrane dynamics. The goal of this work was to directly compare two common fluorescence methods, line-scanning fluorescence correlation spectroscopy and single-particle tracking, to observe the diffusion of a fluorescent lipophilic dye, DiD, in a complex five-component mitochondria-like solid-supported lipid bilayer. We measured diffusion coefficients of \(D_{\text{FCS}} \sim\) 3 \(\upmu\text{m}^2\cdot\text{s}^{-1}\) and \(D_{\text{SPT}} \sim 2 \upmu \text{m}^2\cdot\text{s}^{-1}\), respectively. These comparable, yet statistically different values are used to highlight the main message of the paper, namely that the two considered methods give access to distinctly different dynamic ranges: \(D \gtrsim 1 \upmu \text{m}^2\cdot\text{s}^{-1}\) for FCS and \(D \lesssim 5 \upmu \text{m}^2\cdot\text{s}^{-1}\) for SPT (with standard imaging conditions). In the context of membrane diffusion, this means that FCS allows studying lipid diffusion in fluid membranes, as well as the diffusion of loosely-bound proteins hovering above the membrane. SPT, on the other hand, is ideal to study the motions of membrane-inserted proteins, especially those presenting different conformations, but only allows studying lipid diffusion in relatively viscous membranes, such as supported lipid bilayers and cell membranes.
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Marine Drugs, Vol. 13, Pages 6910-6946: Cyanobactins from Cyanobacteria: Current Genetic and Chemical State of Knowledge
Cyanobacteria are considered to be one of the most promising sources of new, natural products. Apart from non-ribosomal peptides and polyketides, ribosomally synthesized and post-translationally modified peptides (RiPPs) are one of the leading groups of bioactive compounds produced by cyanobacteria. Among these, cyanobactins have sparked attention due to their interesting bioactivities and for their potential to be prospective candidates in the development of drugs. It is assumed that the primary source of cyanobactins is cyanobacteria, although these compounds have also been isolated from marine animals such as ascidians, sponges and mollusks. The aim of this review is to update the current knowledge of cyanobactins, recognized as being produced by cyanobacteria, and to emphasize their genetic clusters and chemical structures as well as their bioactivities, ecological roles and biotechnological potential.
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Marine Drugs, Vol. 13, Pages 6884-6909: Marine Drugs Regulating Apoptosis Induced by Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)
Marine biomass diversity is a tremendous source of potential anticancer compounds. Several natural marine products have been described to restore tumor cell sensitivity to TNF-related apoptosis inducing ligand (TRAIL)-induced cell death. TRAIL is involved during tumor immune surveillance. Its selectivity for cancer cells has attracted much attention in oncology. This review aims at discussing the main mechanisms by which TRAIL signaling is regulated and presenting how marine bioactive compounds have been found, so far, to overcome TRAIL resistance in tumor cells.
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Machines, Vol. 3, Pages 352-363: Double Lighting Machine Vision System to Monitor Harvested Paddy Grain Quality during Head-Feeding Combine Harvester Operation
A machine vision system to evaluate harvested paddy grain quality during harvesting using double lighting was developed. The prototype consisted of a low-cost web camera and two lighting systems: a ring white LED for front lighting, and a flat dome white LED light for backlighting. Both lighting systems were arranged in a coaxial axis, making the system simple, compact and easy to handle. The aim of the system is to analyse the captured images and determine the amount of unwanted materials (rachis branch, grass and leaves, and stems) and damaged grain (brown and crack rice) present in the paddy as it is being harvested. In this paper, we introduce the first step in the development of the system: the design and selection of components to optimize the performance of the system to monitor harvested paddy grain quality. The idea would be to mount the system on top of the inlet channel of the grain tank of a combine harvester to provide real-time assessment of harvesting operational parameters.
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Metals, Vol. 5, Pages 2128-2133: Some Issues in Liquid Metals Research
The ten articles [1–10] included in this Special Issue on "Liquid Metals" do not intend to comprehensively cover this extensive field, but, rather, to highlight recent discoveries that have greatly broadened the scope of technological applications of these materials. Improvements in understanding the physics of liquid metals are, to a large extent, due to the powerful theoretical tools in the hands of scientists, either semi-empirical [1,5,6] or ab initio (molecular dynamics, see [7]). Surface tension and wetting at metal/ceramic interfaces is an everlasting field of fundamental research with important technological implications. The review of [2] is broad enough, as the work carried out at Grenoble covers almost all interesting matters in the field. Some issues of interest in geophysics and astrophysics are discussed in [3]. The recently discovered liquid–liquid transition in several metals is dealt with in [4]. The fifth contribution [5] discusses the role of icosahedral superclusters in crystallization. In [6], thermodynamic calculations are carried out to identify the regions of the ternary phase diagram of Al-Cu-Y, where the formation of amorphous alloys is most probable. Experimental data and ab initio calculations are presented in [7] to show that an optimal microstructure is obtained if Mg is added to the Al-Si melt before than the modifier AlP alloy. Shock-induced melting of metals by means of laser driven compression is discussed in [8]. With respect to recent discoveries, one of the most outstanding developments is that of gallium alloys that are liquid at room temperature [9], and that, due to the oxide layer that readily cover their surface, maintain some "stiffness". This has opened the possibility of 3D printing with liquid metals. The last article in this Special Issue [10] describes nano-liquid metals, a suspension of liquid metal and its alloy containing nanometer-sized particles. A room-temperature nano-liquid metal and its alloys were first introduced in the area of cooling high heat flux devices, which now is a commercial reality. However, their applications are not only in chip cooling, and can also be extended to waste heat recovery, kinetic energy harvesting, thermal interface material, etc. This is mainly due to properties such as low melting point, high thermal and electrical conductivity, as well as other additional physical or chemical properties. These articles are summarized in more detail hereafter [...]
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Energies, Vol. 8, Pages 12881-12897: An Analysis of Decentralized Demand Response as Frequency Control Support under CriticalWind Power Oscillations
In power systems with high wind energy penetration, the conjunction of wind power fluctuations and power system inertia reduction can lead to large frequency excursions, where the operating reserves of conventional power generation may be insufficient to restore the power balance. With the aim of evaluating the demand-side contribution to frequency control, a complete process to determine critical wind oscillations in power systems with high wind penetration is discussed and described in this paper. This process implies thousands of wind power series simulations, which have been carried out through a validated offshore wind farm model. A large number of different conditions have been taken into account, such as frequency dead bands, the percentages of controllable demand and seasonal factor influence on controllable loads. Relevant results and statistics are also included in the paper.
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Climate, Vol. 3, Pages 876-900: A Survey of the Relationship between Climatic Heat Stress Indices and Fundamental Milk Components Considering Uncertainty
The main purpose of this study is to assess the relationship between four bioclimatic indices for cattle (environmental stress, heat load, modified heat load, and respiratory rate predictor indices) and three main milk components (fat, protein, and milk yield) considering uncertainty. The climate parameters used to calculate the climate indices were taken from the NASA-Modern Era Retrospective-Analysis for Research and Applications (NASA-MERRA) reanalysis from 2002 to 2010. Cow milk data were considered for the same period from April to September when the cows use the natural pasture. The study is based on a linear regression analysis using correlations as a summarizing diagnostic. Bootstrapping is used to represent uncertainty information in the confidence intervals. The main results identify an interesting relationship between the milk compounds and climate indices under all climate conditions. During spring, there are reasonably high correlations between the fat and protein concentrations vs. the climate indices, whereas there are insignificant dependencies between the milk yield and climate indices. During summer, the correlation between the fat and protein concentrations with the climate indices decreased in comparison with the spring results, whereas the correlation for the milk yield increased. This methodology is suggested for studies investigating the impacts of climate variability/change on food and agriculture using short term data considering uncertainty.
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Challenges, Vol. 6, Pages 244-257: Human Health Impact of Natural and Artificial Radioactivity Levels in the Sediments and Fish of Bonny Estuary, Niger Delta, Nigeria
There is widespread contamination of the environment of the Niger Delta, which may include enhanced background levels of naturally occurring radioactive materials (NORM) due to oil production and rapid urbanization activities. Sediments and seafood from the Bonny estuary, Niger Delta, were collected for the purpose of determining baseline data on artificial and natural radioactivity and estimation of effective doses for the public due to ingestion of seafood from the study area. The highest and lowest activity concentrations were reported for 40K and 137Cs in both sediments and fish samples of the Bonny estuary. There was some evidence of spatial variability in the 40K and 137Cs data, with the latter being the likely result of dredging. Other radionuclides were not significantly different between sites impacted by industrial activities or not. Activity of radionuclides measured in the sediments of the study area were higher than reported elsewhere in the Niger Delta and Nigeria and higher than reported global averages by UNSCEAR. The total highest activity concentration in all fish species of gamma emitting radionuclides was observed for 40K, followed by 238U, 232Th and 226Ra, respectively, while 137Cs had the lowest activity concentration. However, 210Po activities were the most important in terms of dose contribution. Consumption of molluscs at typical rates could result in doses exceeding 1 mSv·y−1. Although this baseline data may not be conclusive on prevailing trends in radioactivity in the study area, higher consumption rates of the species studied may have public health consequences due to effects of low dose ionising radiation.
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Biology, Vol. 4, Pages 785-813: Methods for Differentiating Prion Types in Food-Producing Animals
Prions are an enigma amongst infectious disease agents as they lack a genome yet confer specific pathologies thought to be dictated mainly, if not solely, by the conformation of the disease form of the prion protein (PrPSc). Prion diseases affect humans and animals, the latter including the food-producing ruminant species cattle, sheep, goats and deer. Importantly, it has been shown that the disease agent of bovine spongiform encephalopathy (BSE) is zoonotic, causing variant Creutzfeldt Jakob disease (vCJD) in humans. Current diagnostic tests can distinguish different prion types and in food-producing animals these focus on the differentiation of BSE from the non-zoonotic agents. Whilst BSE cases are now rare, atypical forms of both scrapie and BSE have been reported, as well as two types of chronic wasting disease (CWD) in cervids. Typing of animal prion isolates remains an important aspect of prion diagnosis and is now becoming more focused on identifying the range of prion types that are present in food-producing animals and also developing tests that can screen for emerging, novel prion diseases. Here, we review prion typing methodologies in light of current and emerging prion types in food-producing animals.
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Galaxies, Vol. 3, Pages 192-201: Back to the Green Valley: How to Rejuvenate an S0 Galaxy through Minor Mergers
About half of the S0 galaxies in the nearby Universe show signatures of recent or ongoing star formation. Whether these S0 galaxies were rejuvenated by the accretion of fresh gas is still controversial. We study minor mergers of a gas-rich dwarf galaxy with an S0 galaxy, by means of N-body smoothed-particle hydrodynamics simulations. We find that minor mergers trigger episodes of star formation in the S0 galaxy, lasting for \(\sim\)10 Gyr. One of the most important fingerprints of the merger is the formation of a gas ring in the S0 galaxy. The ring is reminiscent of the orbit of the satellite galaxy, and its lifetime depends on the merger properties: polar and counter-rotating satellite galaxies induce the formation of long-lived smooth gas rings.
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The Role of Different Cycles of Chemotherapy（Capecitabine-oxaliplatin） in Esophageal Chemoradiotherapy
Interventions: Drug: Capecitabine(Aibin); Drug: Oxaliplatin(Aiheng); Radiation: Radiotherapy
Sponsor: The First Affiliated Hospital of Henan University of Science and Technology
Recruiting - verified July 2015
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Cytological Screening for Early Diagnosis of Precancerous or Cancerous Lesions of Oral Cavity
Intervention: Device: Orcellex® Rovers brush
Sponsor: University Hospital, Toulouse
Recruiting - verified November 2015
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Efficacy and Safety of TC+AVASTIN Versus TC in Patients With Metastatic Nasopharyngeal Carcinoma
Interventions: Drug: Paclitaxel; Drug: Bevacizumab; Drug: Carboplatin
Sponsor: Sun Yat-sen University
Recruiting - verified November 2015
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ADXS 11-001 Vaccination Prior to Robotic Surgery, HPV-Positive Oropharyngeal Cancer
Intervention: Biological: ADXS11-001 (ADXS-HPV)
Sponsors: Andrew Sikora; Advaxis, Inc.
Recruiting - verified November 2015
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Analgesic Effects of Topical Ketamine Mouthwash in Patients Receiving Chemoradiation or Radiotherapy for Head and Neck Cancer
Interventions: Drug: Ketamine; Drug: Placebo
Sponsor: Dartmouth-Hitchcock Medical Center
Recruiting - verified February 2014
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SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
Interventions: Drug: SPI-1005 Low Dose; Drug: SPI-1005 Middle Dose; Drug: SPI-1005 High Dose; Drug: Placebo
Sponsors: Sound Pharmaceuticals, Incorporated; VA Puget Sound Health Care System
Not yet recruiting - verified November 2015
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Radiation Therapy With or Without Cetuximab in Treating Patients Who Have Undergone Surgery for Locally Advanced Head and Neck Cancer
Interventions: Biological: cetuximab; Radiation: intensity-modulated radiation therapy
Sponsors: Radiation Therapy Oncology Group; National Cancer Institute (NCI); NRG Oncology
Recruiting - verified November 2015
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Antibiotics, Vol. 4, Pages 605-616: Remote Antimicrobial Stewardship in Community Hospitals
Antimicrobial stewardship has become standard practice at university medical centers, but the practice is more difficult to implement in remote community hospitals that lack infectious diseases trained practitioners. Starting in 2011, six community hospitals within the Vidant Health system began an antimicrobial stewardship program utilizing pharmacists who reviewed charts remotely from Vidant Medical Center. Pharmacists made recommendations within the electronic medical record (EMR) to streamline, discontinue, or switch antimicrobial agents. Totals of charts reviewed, recommendations made, recommendations accepted, and categories of intervention were recorded. Linear regression was utilized to measure changes in antimicrobial use over time. For the four larger hospitals, recommendations for changes were made in an average of 45 charts per month per hospital and physician acceptance of the pharmacists' recommendations varied between 83% and 88%. There was no significant decrease in total antimicrobial use, but much of the use was outside of the stewardship program's review. Quinolone use decreased by more than 50% in two of the four larger hospitals. Remote antimicrobial stewardship utilizing an EMR is feasible in community hospitals and is generally received favorably by physicians. As more community hospitals adopt EMRs, there is an opportunity to expand antimicrobial stewardship beyond the academic medical center.
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Antibiotics, Vol. 4, Pages 567-604: Co-Selection of Resistance to Antibiotics, Biocides and Heavy Metals, and Its Relevance to Foodborne Pathogens
Concerns have been raised in recent years regarding co-selection for antibiotic resistance among bacteria exposed to biocides used as disinfectants, antiseptics and preservatives, and to heavy metals (particularly copper and zinc) used as growth promoters and therapeutic agents for some livestock species. There is indeed experimental and observational evidence that exposure to these non-antibiotic antimicrobial agents can induce or select for bacterial adaptations that result in decreased susceptibility to one or more antibiotics. This may occur via cellular mechanisms that are protective across multiple classes of antimicrobial agents or by selection of genetic determinants for resistance to non-antibiotic agents that are linked to genes for antibiotic resistance. There may also be relevant effects of these antimicrobial agents on bacterial community structure and via non-specific mechanisms such as mobilization of genetic elements or mutagenesis. Notably, some co-selective adaptations have adverse effects on fitness in the absence of a continued selective pressure. The present review examines the evidence for the significance of these phenomena, particularly in respect of bacterial zoonotic agents that commonly occur in livestock and that may be transmitted, directly or via the food chain, to human populations.
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Biomolecules, Vol. 5, Pages 3177-3192: Fluorinated Carbohydrates as Lectin Ligands: 19F-Based Direct STD Monitoring for Detection of Anomeric Selectivity
The characterization of the binding of reducing carbohydrates present as mixtures of anomers in solution to a sugar recepor (lectin) poses severe difficulties. In this situation, NMR spectroscopy enables the observation of signals for each anomer in the mixture by applying approaches based on ligand observation. Saturation transfer difference (STD) NMR allows fast and efficient screening of compound mixtures for reactivity to a receptor. Owing to the exceptionally favorable properties of 19F in NMR spectroscopy and the often complex 1H spectra of carbohydrates, 19F-containing sugars have the potential to be turned into versatile sensors for recognition. Extending the recently established 1H → 1H STDre19F-NMR technique, we here demonstrate its applicability to measure anomeric selectivity of binding in a model system using the plant lectin concanavalin A (ConA) and 2-deoxy-2-fluoro-d-mannose. Indeed, it is also possible to account for the mutual inhibition between the anomers on binding to the lectin by means of a kinetic model. The monitoring of 19F-NMR signal perturbation disclosed the relative activities of the anomers in solution and thus enabled the calculation of their binding affinity towards ConA. The obtained data show a preference for the α anomer that increases with temperature. This experimental approach can be extended to others systems of biomedical interest by testing human lectins with suitably tailored glycan derivatives.
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Water, Vol. 7, Pages 6483-6495: Effect of Ultrasound Pretreatment on Sludge Digestion and Dewatering Characteristics: Application of Particle Size Analysis
The aim of this work was to study the effect of ultrasonic pretreatment on sludge digestion, particle size distribution (PSD), and dewaterability of digestates (measured by capillary suction time (CST) and specific resistance to filtration (SRF)). Sludge was pretreated with ultrasound (24 kHz) at an energy dosage of 4300 kJ/kg TS. Digestibility of sludge was increased by ultrasound pretreatment resulting in a higher specific methane production (SMP). The digestate of pretreated waste activated sludge (WAS) obtained under batch conditions presented a better dewatering performance. Digestion under semi-continuous conditions was evaluated using sewage sludge (mixture of primary sludge and WAS). In this case, digestates presented a much higher mean particle size for both cases evaluated (pretreated and non-pretreated) than that obtained under batch conditions. A wide PSD was a characteristic of these digestate samples. Flow dynamics inside the reactor resulted in the presence of high-diameter flocs, thus significantly affecting the mean particle size and specific surface area (SSA) values.
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Water, Vol. 7, Pages 6467-6482: Obtaining the Thermal Structure of Lakes from the Air
The significance of thermal heterogeneities in small surface water bodies as drivers of mixing and for habitat provision is increasingly recognized, yet obtaining three-dimensionally-resolved observations of the thermal structure of lakes and rivers remains challenging. Remote observations of water temperature from aerial platforms are attractive: such platforms do not require shoreline access; they can be quickly and easily deployed and redeployed to facilitate repeated sampling and can rapidly move between target locations, allowing multiple measurements to be made during a single flight. However, they are also subject to well-known limitations, including payload, operability and a tradeoff between the extent and density over which measurements can be made within restricted flight times. This paper introduces a novel aerial thermal sensing platform that lowers a temperature sensor into the water to record temperature measurements throughout a shallow water column and presents results from initial field experiments comparing \emph{in situ} temperature observations to those made from the UAS platform. These experiments show that with minor improvements, UASs have the potential to enable high-resolution 3D thermal mapping of a \(\sim\)1-ha lake in 2–3 flights (\textit{circa} 2 h), sufficient to resolve diurnal variations. This paper identifies operational constraints and key areas for further development, including the need for the integration of a faster temperature sensor with the aerial vehicle and better control of the sensor depth, especially when near the water surface.
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Behavioral Sciences, Vol. 5, Pages 518-536: Types of Relational Aggression in Girls Are Differentiated by Callous-Unemotional Traits, Peers and Parental Overcontrol
Adolescent girls often perpetrate aggression by gossiping and spreading rumours about others, by attempting to ruin relationships and by manipulating and excluding others. Further, males and females engage in reactive and proactive relational aggression differently. In this study, we examined the individual, peer and parental contextual factors that best explained the use of reactive and proactive relational aggression in girls. Female participants (n = 614; ages 11–18 years) completed questionnaires on aggression, callous-unemotional (CU) traits, delinquency, peer delinquency, gender composition of their peer group, resistance to peer influence and perceived parental overcontrol. Multinomial logistic regression was used to examine the effects of individual, peer- and parent-related variables on the likelihood of being classified as a low aggressor, reactive aggressor or proactive/reactive aggressor. Girls in the combined reactive/proactive aggression group were younger, had greater CU traits, a lower proportion of male peers and greater perception of parental control than both the reactive and low aggressive groups. Both highly aggressive groups were more delinquent and had greater peer delinquency than the low aggressive group. This study suggests those girls who show relational aggression for the purpose of gaining status and revenge feel restrained by their parents and may gravitate toward relationships that support their behaviour.
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Modélisation de l’impact économique d’un dépistage organisé du cancer du poumon en France
Publication date: Available online 12 November 2015
Source:Revue des Maladies Respiratoires
Author(s): S. Gendarme, É. Perrot, F. Reskot, V. Bhoowabul, G. Fourre, P.-J. Souquet, B. Milleron, S. Couraud
IntroductionL'étude National Lung Screening Trial (NLST) a montré que, dans une population à haut risque de cancer bronchique, un scanner à faible dose annuel permettait de réduire la mortalité par cancer bronchique de 20 % et la mortalité totale de 7 %. En France, un groupe d'experts s'est prononcé en faveur de la réalisation d'un dépistage individuel. Toutefois, l'impact « économique » d'un dépistage organisé en France n'a jamais été rapporté.Matériel et méthodesIl s'agit d'une étude de modélisation à partir des données démographiques de la population française et des données publiées. Les critères de sélection de la population étaient ceux de l'étude NLST (fumeurs âgés de 55–74ans, au moins 30 paquets-années, avec tabagisme en cours ou sevrés depuis moins de 15ans). Un second modèle élargi aux sujets âgés de 50–54ans a été calculé. Plusieurs taux de participation ont été ensuite utilisés : 65 %, 45 % et 32 %.RésultatsEn fonction du modèle, la population éligible serait de 1 650 588 à 2 283 993 individus. En fonction du modèle et du niveau de participation, le dépistage conduirait à diagnostiquer chaque année entre 3600 et 10 118 cancers de stades I à II. Le nombre respectif de faux-positifs varierait de 5991 à 16 839 dont 1416 à 3981 pourraient subir une chirurgie « inutile ». Le dépistage coûterait entre 105 et 215 millions d'euros par an.ConclusionLa participation est un élément décisif de l'impact du dépistage du cancer bronchique. Ce dernier pourrait être financé par une augmentation minime du prix du tabac. Ce coût pourrait être supporté par une élévation de 0,05 à 0,10 € du prix du paquet de cigarette.IntroductionThe National Lung Screening Trial found that, in a selected population with a high risk of lung cancer, an annual low-dose CT-scan decreased lung cancer mortality by 20% and overall mortality by 7% compared to annual chest X-Ray. In France, a work group stated that individual screening should be considered in this setting. However, the economic impact of an organized and generalized (to all eligible individuals) screening in France was never reported.MethodsThis is a modeling study using French population demographic data and published data from randomized screening trials. We used the same selection criteria as NLST: 55–74-year-old smokers for at least 30 pack-years, current smoker or quit less than 15 years. We computed a second model including also 50–54-year-old individuals. Then, we used different participation rates: 65%, 45%, and 32%.ResultsAccording to the considered model, there would be 1,650,588 to 2,283,993 subjects eligible to screening in France. According to the model and participation rate, lung cancer screening would diagnose 3600 to 10,118 stages 1/2 lung cancer each year. There would be 5991 to 16,839 false-positives, of whom 1416 to 3981 would undergo unnecessary surgery. Screening policy would cost 105 to 215 € million per year. However, increasing the price of a cigarette pack by 0.05 to 0.10 € would fully cover the screening costs.ConclusionParticipation rate is a key point for screening impact. Screening could be easily funded by a small increase in cigarette prices.
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Delayed onset of electromyographic activity of the vastus medialis relative to the vastus lateralis may be related to physical activity levels in females with patellofemoral pain
Publication date: Available online 12 November 2015
Source:Journal of Electromyography and Kinesiology
Author(s): Ronaldo Valdir Briani, Danilo de Oliveira Silva, Marcella Ferraz Pazzinatto, Amanda Schenatto Ferreira, Deisi Ferrari, Fábio Mícolis de Azevedo
The aims of this study were to examine group differences in muscle activation onset of the vastus medialis (VM) in relation to the vastus lateralis (VL) and pain level during stair ascent in females with patellofemoral pain (PFP) who maintain high and moderate levels of physical activity; to determine the association between physical activity level and muscle activation onset. Forty-three females with PFP and thirty-eight pain-free females were recruited and divided into four groups based on their level of physical activity: females with PFP(n=26) and pain-free females(n=26) who practiced a moderate level of physical activity and females with PFP(n=17) and pain-free females(n=12) who practiced an intense amount of physical activity. Participants were asked to ascend a seven-step staircase and the VM and VL activation onset was determined. Females with PFP who practiced high level of physical activity demonstrated delayed onset of VM (4.06ms) compared to healthy females (-14.4ms). Conversely, females with PFP who practiced moderate level of physical activity did not present VM delay (-2.48ms) in comparison to healthy females(-9.89ms). Furthermore, physical activity significantly correlated to the muscle activation onset difference (p=0.005; R=0.60). These findings may explain why controversial results regarding VM and VL muscle activation onset have been found.
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Acute mountain sickness and obesity
L'articolo Acute mountain sickness and obesity sembra essere il primo su European Review.
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Reduced expression of miR-503 is associated with poor prognosis in cervical cancer
OBJECTIVE: We wished to evaluate the association between expression of microRNA (miR) -503 and prognosis in patients with cervical cancer.
PATIENTS AND METHODS: 96 paired specimens of cervical cancer and adjacent normal cervical epithelial tissues were obtained. qPCR was used to evaluate expression levels of miR-503. We analyzed the associations between miR-503 expression levels and clinicopathological parameters, as well as recurrence-free and overall survival with Kaplan-Meier survival curves and proportional hazards model.
RESULTS: miR-503 levels were significantly (p < 0.001) lower in cervical cancer tissue compared with adjacent normal cervical epithelial tissue. We further observed significant associations of expression of this miR and recurrence of cervical cancer, lymph node metastasization, and International Federation of Gynecology and Obstetrics (FIGO) stage. In addition, in multivariate analysis, miR-503 expression level was found to be an independent prognostic factor for both recurrence-free and overall survival.
CONCLUSIONS: Reduced expression of miR-503 is an independent prognostic factor in cervical cancer indicating poor prognosis.
L'articolo Reduced expression of miR-503 is associated with poor prognosis in cervical cancer sembra essere il primo su European Review.
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Decreased preoperative serum fibulin-3 levels in colon cancer patients
OBJECTIVE: Fibulin-3 is known to play a role in tumor cell malignancy, invasion and metastasis, as well as in the clinical progression of tumors. This study aimed to assess serum fibulin-3 levels in patients with colon cancer compared with healthy controls and its relationship to demographics and tumor pathology.
PATIENTS AND METHODS: A total of 80 patients (mean age, 58.99 years; 42% males) with colon cancer and 50 controls (mean age, 57.75; 55% males) were included. Serum levels of fibulin-3 were determined using a commercially available sandwich ELISA (Enzyme-Linked ImmunoSorbent Assay).
RESULTS: Preoperative serum fibulin-3 levels were significantly lower in the group of patients with colon cancer (mean, 35.91 ng/mL; range, 10-73 ng/mL) compared with the control group (mean, 96.68 ng/mL; range, 57-168 ng/mL).
CONCLUSIONS: It was concluded that fibulin-3 is expressed at a lower level in colon cancer, and it can serve as a marker for advanced colon cancer.
L'articolo Decreased preoperative serum fibulin-3 levels in colon cancer patients sembra essere il primo su European Review.
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Oxidative stress inhibits growth and induces apoptotic cell death in human U251 glioma cells via the caspase-3-dependent pathway
OBJECTIVE: To investigate the possible pathway involved in hydrogen peroxide (H2O2) induced apoptosis in U251 glioma cells.
MATERIALS AND METHODS: The cultured U251 glioma cells were used in this study. The cells were divided into three groups: control group (untreated glioma cells), H2O2 group (treated with 100, 300 and 500 µM H2O2) and CI group (treated with 300 µM H2O2 and 15 µM caspase inhibitor, CI). The cellular viability was determined by MTT [3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide] assay. A flow cytometer was used for measuring the cell cycles. The mode of cell death was assessed by Annexin-V/PI-flow cytometry analysis. Fluorescence dihydroethidium (DHE) method was conducted to detect the oxygen species (O2–). Western blot analysis was performed to confirm the pro-caspase-3, caspase-3 and PARP (poly-ADP-ribose polymerase) protein expression.
RESULTS: The oxidative stress to U251 glioma cells exhibited in a dose-dependent manner with H2O2 concentrations increasing. The cell viability was considerably decreased and apoptosis occurred in H2O2 treated cells. A G1 cell cycle arrest and O2– level increase were found in H2O2 group. Western blot analysis showed a decrease of pro-caspase-3 protein level and an increase of caspase-3 and PARP level in 300 µM H2O2 treated cells. The H2O2 induced apoptosis depicted above was significantly restrained by CI.
CONCLUSIONS: Oxidative stress inhibits growth and induces apoptotic cell death in human U251 glioma cells via the caspase-3-dependent pathway. Mitochondrial pathway might involve in this signaling conduction. These findings are favorable for understanding the mechanisms of oxidative stress-induced apoptosis in U251 glioma cells.
L'articolo Oxidative stress inhibits growth and induces apoptotic cell death in human U251 glioma cells via the caspase-3-dependent pathway sembra essere il primo su European Review.
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Cancer stem cells targeting agents – a review
Major current cancer strategies like surgery, radiotherapy, and chemotherapy are compromised due to major problem of recurrence, which usually lead to mortality. The widely accepted reason for this is resistance offered by cancer cells towards cancer drugs or inability of a therapeutic procedure to target real culprits viz. cancer-initiating cells (cancer stem cells). So, there is a current need of development of new agents targeting these cancer stem cells in order to overcome resistance to therapeutic procedures.
The present review article is focused on new cancer cell targeting agents like salinomycin, apopotin etc and their mechanisms to target cancer stems cells will be discussed.
L'articolo Cancer stem cells targeting agents – a review sembra essere il primo su European Review.
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Focus on biological identity of endothelial progenitors cells
Circulating Endothelial Progenitor Cells (EPCs) were discovered by Asahara et al in 1997 and defined as bone marrow CD34+/KDR+ cells endowed with angiogenic potentialities in vitro and in vivo. The most likely assumption is that EPCs consist of several cell subpopulations with functions targeted at accomplishing the post-natal neovascularization process in a synergic and complementary fashion. Indeed, the subsequent identification of numerous and differentiated hematic populations, characterized by the capacity to develop an endothelial phenotype, has posed a number of questions as to the real identity of EPCs. This concept does not represent a sterile speculation but rather it suggests important implications for the future practice of stem cell therapy.
The aim of this report was to explore, through a critical analysis, the two main experimental methodologies, in vitro culture and flow cytometry, applied to EPCs, followed by a brief revaluation of the endothelial progenitors employing a globally functional approach.
L'articolo Focus on biological identity of endothelial progenitors cells sembra essere il primo su European Review.
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An extracellular matrixcculture system for induced pluripotent stem cells derived from human dental pulp cells
OBJECTIVE: Induced pluripotent stem cells (iPSCs) have emerged as a promising tool for treating incurable diseases. The current challenges are to avoid potential xenopathogenic transmission and immune rejection potentially caused by exposure of iPSCs to animal-derived products. In addition, an efficient feeder cell-free culture condition will be required for minimizing batch-to-batch variation and facilitating scale-up. Therefore, establishing an efficient extracellular matrix (ECM) culture system is considered as a prerequisite for the future clinical application of iPSC-based cell therapies. In this study, we evaluated the feasibility of culturing iPSCs in ECM derived from human dental pulp cells.
MATERIALS AND METHODS: iPSCs growing in Matrigel were transferred to ECM or Matrigel and cultured in mTeSRTM1 medium.
RESULTS: The number of adherent cells in the ECM group was higher than that in the Matrigel group after incubation for 8, 12, and 24 h, indicating that the ECM could enhance cell adherence. The adhesion of cells to ECM not only depends on simple physical attachment with ECM but also mediated by fibronectin in the ECM. The hDPC-iPSCs showed orderly growth in the ECM, suggesting that the ECM could promote the growth and proliferation of hDPC-iPSCs. We also observed that stem cells growed along to avoid contact inhibition.
CONCLUSIONS: The iPSCs maintained undifferentiated state when cultured in ECM when the iPSCs and ECM are of the same cell origin. ECM and mTeSRTM1, can both be used as new culture medium for iPSCs that facilitates the clinical application of iPSC-based cell therapies in the future.
L'articolo An extracellular matrixcculture system for induced pluripotent stem cells derived from human dental pulp cells sembra essere il primo su European Review.
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Prions mediated neurodegenerative disorders
Prions are unprecedented infectious pathogens that are devoid of nucleic acid and cause a group of rare and invariably fatal neurodegenerative disorders, affecting approximately 1 person per 1 million inhabitants annually worldwide. These disorders include Creutzfeld-Jacob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), kuru, fatal insomnia (FI), and variable protease-sensitive prionopathy (VPSPr), all of which involve a conformational change of the normal cellular prion protein (PrPC) into the abnormal scrapie prion protein (PrPSc) through a posttranslational process during which PrPc acquires high β-sheet content. This structural change is accompanied by profound changes in the physicochemical properties of PrPC, rendering the molecule resistant to proteolysis. The conformational change of PrPC can occur due to either spontaneous conversion, dominant mutations in the prion protein (PRNP) gene encoding PrPC, or infection with pathogenic isoform PrPsc from exogenous sources. There is general agreement that PrPC serves as a substrate for conversion to abnormal PrPSc. This latter multiplies exponentially and aggregates in the brain, forming deposits that are associated with the neurodegenerative changes. Although the understanding of the primary causes of prion-induced neurodegeneration is still limited, propagation of PrPSc and neurotoxic signaling seem to interplay in pathogenic process of prions. Here, we review recent findings that have provided fresh insights into this process, and present an overview of incidence, causes and spectrum of related disorders.
L'articolo Prions mediated neurodegenerative disorders sembra essere il primo su European Review.
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MiR-16 regulates cell death in Alzheimer’s disease by targeting amyloid precursor protein
OBJECTIVE: The aim of this study was to investigate the role of miR-16 in Alzheimer's disease (AD) and to explore its mechanism of action.
MATERIALS AND METHODS: A cellular AD model using PC12 cells and primary hippocampal neurons was established to evaluate the expression level of miR-16. Transfection of a miR-16 mimic and a miR-16 inhibitor were performed to explore its effect on cell apoptosis and cell viability. In addition, we carried out bioinformatics analysis, luciferase reporting gene assay, and gene expression analyses to identify the potential target of miR-16 and to verify the effect of the target gene on the cellular AD model.
RESULTS: Downregulation of miR-16 was confirmed in the cellular AD model with both PC12 cells (p < 0.05) and primary hippocampal neurons (p < 0.05). Overexpression and inhibition of miR-16 in the cellular AD model with primary hippocampal neurons decreased and increased apoptosis, respectively. The gene encoding amyloid precursor protein (APP) was identified as the target gene of miR-16. Knockdown of APP in primary hippocampal neurons decreased cell apoptosis and increased cell viability in the cellular AD model.
CONCLUSIONS: Our results demonstrate that downregulation of miR-16 in primary hippocampal neurons play an important role in the paracrine effect and might be involved in the development of AD.
L'articolo MiR-16 regulates cell death in Alzheimer's disease by targeting amyloid precursor protein sembra essere il primo su European Review.
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Identification of therapeutic targets of ischemic stroke with DNA microarra
OBJECTIVE: Ischemic stroke (IS) is a complex disease that resulting from the interaction of various environmental and genetic risk factors. As genetic factors exerting a direct contributory role in IS, it is one of the focus areas of identification the genetic factors of IS. This study aimed to screen bio-targets of ischemic stroke (IS), and to identify related drug molecules.
MATERIALS AND METHODS: The gene expression profile GSE22255 was downloaded from Gene Expression Omnibus (GEO) database, including 20 whole blood samples from ISpatients (IS group) and 20 samples from healthy controls (control group). Differentially expressed genes (DEGs) were screened out using limma package in R. Hierarchical clustering and differences between the groups analysis were conducted for confirming these DEGs. Database for Annotation, Visualization and Integrated Discovery (DAVID) and Kyoto Enrichment of Genes and Genomes (KEGG) were used to obtain the functional genes and pathways respectively. The DEGs were then entered into the WebGestalt database and related drug molecules were retrieved.
RESULTS: Compared with the control group, 27 DEGs were identified from IS group including 25 up- and 2 down-regulated genes. Then functions and pathways enrichment analysis for DEGs were conducted and TNF, IL1B and TNFAIP3 were found to be both participate in apoptosis and NOD-like receptor signaling pathway. Finally, collagenase and other most-related drug molecules were identified from the DEGs.
CONCLUSIONS: In addition to DEGs, several drug molecules were retrieved, which may be related with stroke. Our study provides some underlying bio-targets such as TNF, IL1B and TNFAIP3 for IS and potential drug molecules such as collagenase for the treatment of IS.
L'articolo Identification of therapeutic targets of ischemic stroke with DNA microarra sembra essere il primo su European Review.
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Materials, Vol. 8, Pages 7714-7722: A Novel Biodegradable Polycaprolactone Fixator for Osteosynthesis Surgery of Rib Fracture: In Vitro and in Vivo Study
Osteosynthesis surgery for rib fractures is controversial and challenging. This study developed a noval poly(ε-caprolactone) (PCL)-based biodegradable "cable-tie" fixator for osteosynthesis surgery for rib fractures. A biodegradable fixator specifically for fractured ribs was designed and fabricated by a micro-injection molding machine in our laboratory. The fixator has three belts that could be passed through matching holes individually. The locking mechanism allows the belt movement to move in only one direction. To examine the in vitro biomechanical performance, ribs 3–7 from four fresh New Zealand rabbits were employed. The load to failure and stress-strain curve was compared in the three-point bending test among native ribs, titanium plate-fixed ribs, and PCL fixator-fixed ribs. In the in vivo animal study, the sixth ribs of New Zealand rabbits were osteotomized and osteosynthesis surgery was performed using the PCL fixator. Outcomes were assessed by monthly X-ray examinations, a final micro-computed tomography (CT) scan, and histological analysis. The experimental results suggested that the ribs fixed with the PCL fixator were significantly less stiff than those fixed with titanium plates (p < 0.05). All ribs fixed with the PCL fixators exhibited union. The bridging callus was confirmed by gross, radiographic micro-three-dimensional (3D) CT, and histological examinations. In addition, there was no significant inflammatory response of the osteotomized ribs or the PCL-rib interface during application. The novel PCL fixator developed in this work achieves satisfactory results in osteosynthesis surgery for rib fractures, and may provide potential applications in other orthopedic surgeries.
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Materials, Vol. 8, Pages 7702-7713: Preparation, Mechanical and Thermal Properties of Cement Board with Expanded Perlite Based Composite Phase Change Material for Improving Buildings Thermal Behavior
Here we demonstrate the mechanical properties, thermal conductivity, and thermal energy storage performance of construction elements made of cement and form-stable PCM-Rubitherm® RT 28 HC (RT28)/expanded perlite (EP) composite phase change materials (PCMs). The composite PCMs were prepared by adsorbing RT28 into the pores of EP, in which the mass fraction of RT28 should be limited to be no more than 40 wt %. The adsorbed RT28 is observed to be uniformly confined into the pores of EP. The phase change temperatures of the RT28/EP composite PCMs are very close to that of the pure RT28. The apparent density and compression strength of the composite cubes increase linearly with the mass fraction of RT28. Compared with the thermal conductivity of the boards composed of cement and EP, the thermal conductivities of the composite boards containing RT28 increase by 15%–35% with the mass fraction increasing of RT28. The cubic test rooms that consist of six boards were built to evaluate the thermal energy storage performance, it is found that the maximum temperature different between the outside surface of the top board with the indoor temperature using the composite boards is 13.3 °C higher than that of the boards containing no RT28. The thermal mass increase of the built environment due to the application of composite boards can contribute to improving the indoor thermal comfort and reducing the energy consumption in the buildings.
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Prognostic performance of different lymph node staging systems after curative intent resection for gastric adenocarcinoma
Annals of Surgery
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A computational chemistry perspective on the current status and future direction of hepatitis B antiviral drug discovery
Antiviral Research
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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